Introduction
Prof. J. L. Chertkov (1927–2009) devoted most of his efforts to understanding the mechanisms of hematopoiesis. He was interested in the developmental fate of hematopoietic stem cells (HSC), and the result of his investigations became the theory of clonal succession of HSC, which was published in several papers [1-4]. The data showed that long-term hematopoiesis is maintained by a large number of simultaneously functioning small, short-lived (1 to 3 months) clones that usually grow locally with little or no dispersion between different regions of the hematopoietic system. Only 10% of clones are long-lived and can function during the whole life of the animal. Furthermore, clones that disappear are never detected again. The data suggests that normal hematopoiesis is supported by the sequential recruitment of marrow repopulating cells into a differentiation mode.
In the mid 1970s, together with A. J. Friedenstein, Joseph Chertkov laid the foundation for experimentation into the differences between HSC and precursor cells in the hematopoietic microenvironment. He postulated that an understanding of the interrelationship between the stem cells of hematopoiesis and regulatory stromal microenvironment is necessary for an investigation of the process of hematopoiesis. To analyze the stromal precursor cells J. L. Chertkov used a functional assay where the microenvironment is addressed as the territory where hematopoiesis takes place and therefore could be estimated by the number of hematopoietic cells maintained on it. The method of ectopic hematopoietic foci formation provides a separate hematopoietic territory built de novo via special stromal precursor cells. Cells capable of transferring the hematopoietic microenvironment were referred to by Chertkov as hematopoietic microenvironment-transferring units (HMTU) [5].
In 1991 A. Caplan defined stem cells capable of giving rise to skeletal tissues – cartilage, bone, tendon, ligament, marrow stroma, and connective tissue – as mesenchymal stem cells (MSC) [6]. The term MSC was used in the fields of cytotherapy and tissue engineering widely and not always correctly; therefore the International Society of Cellular Therapy postulated the use of the term MSC only for cells that fulfilled the stem cell criteria: multipotentiality and self-renewal [7]. All works of Prof. Chertkov clearly demonstrate that HMTU and MSC are synonyms. Therefore we will use the term MSC for cells described by J. L. Chertkov as HMTU.
The compilation of the works by J. L. Chertkov characterizes MSCs both quantitatively and qualitatively, based on their functional properties. MSCs were shown to have a high proliferative potential, to be able to develop multilineage progeny, and form a fully functional hematopoietic microenvironment. The compartment of stromal precursor cells was shown to have a hierarchical structure, and inducible precursor cells were characterized. The radiosensitivity of MSCs and their progeny was estimated and it was then possible to calculate the direct number of MSC in the murine femur.
Materials and Methods
Mice
Female and male C57BL/6 (B6), CBA, CBAT6T6, (CBAxC57BL/6) F1 hybrid (CB), and (CBAT6T6xC57BL/6) F1 hybrid (CBT) mice 8–25 wks of age at the beginning of the study were used. Care was taken that the groups to be compared originated from the same batch of animals housed under the same conditions.
Irradiation of mice
In some of the experiments the recipient mice were irradiated with 400 or 700 rad from a 137Cs IPK irradiator 3 to 4 hrs before bone marrow (BM) implantation. Both doses produced the same effect on the size of the ectopic foci. The irradiator consisted of four 137Cs sources set in a quadrilateral arrangement about the site of exposure.
In order to obtain blood sera containing stroma-stimulating activity, the mice were irradiated with 6–12 Gy (in the latter case the protective dose of BM cells was injected i.v.).
Bone marrow irradiation
In the case of an in vivo irradiation the mice were irradiated and sacrificed immediately thereafter. The femurs were removed and stored on ice until transplantation. For in vitro irradiation the femurs were exposed either to γ-rays from an IPK irradiator with the absorbed dose rate of 500 rad/min or to fast neutrons generated by the Obninsk BR-10 research reactor. The mean energy of fast neutrons was 0.85MeV, the power of the tissue Kerma 128 rad/min, and the ratio of neutron to γ-ray doses at the point of exposure of the bones was approximately 20:1. The γ-ray component was ignored in calculating the dose-response curves, and all neutron doses represent the rad dose of the neutron component. In all experiments, the period between bone resection and the implantation of the bone marrow did not exceed 5 hrs. The sequence of implantation of femurs exposed to various doses was always randomized.
Chimeras
The mice were exposed to 12–13 Gy and reconstituted with syngeneic or allogeneic BM in doses indicated in the corresponding part of the text. In general, 1/3–1/4 of the femoral equivalent was injected (standard chimeras). Secondary chimeras were obtained when irradiated recipients were reconstituted with hematopoietic cells of standard chimeras; the cells were collected no earlier than 2 months after the creation of the standard chimeras. Tertiary chimeras were obtained when the irradiated recipients were reconstituted with hematopoietic cells of secondary chimeras; the cells were also collected no earlier than 2 months after the creation of the secondary chimeras. Double chimeras were obtained when the standard chimeras were exposed to a dose of 12–13 Gy 2–5 months after creation of the chimera, and reconstituted with hematopoietic cells of normal mice. The stromal precursors were studied 3–9 months after creation of the chimeras.
Bone marrow or adherent cell layer implantation
Implantation was performed under the renal capsule of anesthetized mice. The femurs were freed of muscle, the epiphyses cut away, and the bones stored on ice until used. The BM was pressed out of the femur with a stylet or thick needle with a blunt end. In anesthetized mice a small tear was made in the renal capsule and a bone marrow plug or adherent cell layer (ACL) from long-term bone marrow culture placed under it with a small spatula. The ACL was removed from the flask bottom with a rubber policeman and implanted under the renal capsule without conversion to a single-cell suspension. In cases of ectopic foci reimplantation the whole focus was removed from the kidney and implanted under the renal capsule of the recipient. In cases where suspended BM was implanted, the 0.5 ml of suspension (made by repeated passage through a 23-gauge needle) containing 1–2x107 cells was precipitated via centrifugation onto a Millipore HA filter (0.45 micron). The filter was folded so that the cells were inside it and then was transplanted under the renal capsule of the recipient mice. The size of the foci produced was determined after 1–1.5 months by counting the number of nucleated hematopoietic cells in them. The ossicle containing BM was removed from the kidney, and the cells were scraped off the bone with a scalpel into medium 199 or α-MEM and prepared as a single cell suspension by passing it repeatedly through a syringe fitted with a 21-gauge needle. In some experiments the cellularity of the foci was determined in the pool of all foci in each group; consequently, the standard error cannot be calculated. In general the error in such experiments was about 20%.
Bone marrow ablation
After anesthesia, a small incision was made over the knee joint, and the medullary cavity of the femur was entered and curetted using a dental root-canal broach. This was followed by the insertion of a 23-gauge needle into the medullary cavity of the curetted femur, which was then irrigated vigorously with 1 ml of medium 199.
Determination of the proliferative activity of stromal precursors in vivo
The S-phase specific cytostatic compound methotrexate (MTX) was injected intraperitoneally in a single dose of 0.25 mg/g. This dose of MTX was lethal and therefore 4 hrs after its injection the bone marrow or ectopic site was transferred into a normal recipient.
Long-term bone marrow culture
The marrow cells or the cells of an ectopic hematopoietic focus were cultivated by the method described by Dexter et al. [8]. The cells were flushed out with 10 ml of complete medium into a 25cm2 flask without converting them to a single-cell suspension. In the case of cultivation of suspended BM cells, 1 femur was suspended by repeated passage through a 21-gauge needle and then seeded onto the 25cm2 flask. When cultivated in a 24-well plate, 2 femurs were explanted per plate, also without conversion into a single-cell suspension. Fisher medium supplemented with L-glutamine, antibiotics (all Flow Labs), 25% serum (2:1, horse: fetal calf sera, Gibco and Flow Labs) and 10-6M hydrocortisone sodium hemisuccinate (Sigma) were used. The culture was kept at 330C and 5% of CO2 with weekly replacement of 50% of the medium.
The “wound” was performed by scraping 1/2of the adherent cell layer (ACL) with the rubber policeman.
Determination of the proliferative activity of stromal precursors in vitro
Hydroxyurea was added to a long-term bone marrow culture (LTBMC) at the concentration of 13mM (1mg/ml) for periods from 2 hr to 7 days. To stop the function of hydroxyurea the ACLs were washed 3 times with 5 ml of medium 199 with 2% of FCS.
Cytokine treatment
Cytokines (recombinant rat SCF (Amgen) and recombinant human G-CSF (Neupogen 48, Amgen)) were dissolved into the 0.9% NaCl solution with 0.1% of BSA and injected once a day under the skin for 6, 10, or 17 days. G-CSF was used at the concentration of 250 mkg/kg, and SCF at 34 mkg/kg. The control group was injected with 0.9% NaCl solution with 0.1% of BSA only. Twenty hours or 1 month after the last injection, BM from the femurs of the control and cytokine-treated mice was implanted under the renal capsule of the syngeneic mice. In order to define the effect of G-CSF on foci formation the mice were implanted with the syngeneic BM 1 day before beginning the G-CSF courses, which lasted 10 or 17 days.
Sera from irradiated mice
Blood was obtained from the femoral vein not earlier than 1 week after the irradiation. After the clot retraction sera were centrifuged (3000 rpm), supernatant was sterilized by filtration through 0.22 µm filters.
Analysis of various organs of irradiated mice for stroma-stimulating activity
Bone marrow, thymus, bones, liver, and spleen of irradiated mice were implanted into intact mice under the skin or renal capsule. Suspended spleen cells were injected intravenously to the mice previously treated with heparin (50 U/mouse). Intact BM was implanted simultaneously under the renal capsule of these mice.
Karyotype analysis
The origin of the hematopoietic cells in the focus was determined according to the presence or absence of Y-chromosomes, using the G-banding technique.
Histology
The kidneys were removed and fixed in Carnoy’s solution, decalcified, embedded in paraffin and cut into series of 5 µm sections. The preparations were stained with Pappenheim, Giemsa, and hematoxylin-eosin stains.
Statistics
The radiosensitivity curves were fitted to the data via linear regression analysis, from which the D0s, standard errors, and extrapolation numbers were calculated. The concentration of MSC in the femur was calculated using Poisson’s distribution. When not otherwise noted, the data were analyzed with Student’s t-test.
Results and Discussion
Methods of in vitro and in vivo mesenchymal stem cells analysis
In the case of bone marrow (BM) implantation under the renal capsule of the syngeneic animal, the hematopoietic cells leave the graft, whereas the stromal precursors form the new hematopoietic stroma, which is then repopulated by host cells [9, 10]. The same processes take place after implantation of an adherent cell layer from 3–4 wk bone marrow cultures. The beginning of vessel formation was evident by 12 h after implantation. The blood supply to the implant was established 24–48 h after implantation. Characteristic connective tissue lacunae form, and clusters of connective tissue cells were seen from day 4–5, as well as strands of fibroblasts and sometimes the beginning of cartilage development, which was replaced by osteogenesis. By day 6 the implant on the side toward the kidney contained many dead cells with pyknotic nuclei, many erythrocytes, and colonies of hemopoietic cells with blasts cells in the center. On the top and sides of the implant cancellous bone formation was observed. Within the foci there were individual osteoblasts in broad cavities with developing bone trabeculae around them. Osteogenesis was very intensive and 1–2 days later large areas of de novo formed bone could be observed. After 11 days, the typical bone marrow structures such as sinusoids, adipocytes, and areas of hemopoietic cells of different lines of differentiation were represented, and by the end of the second week a well-developed ectopic hemopoietic foci was created [11].
Polymorphic hemopoiesis is maintained for many weeks in long-term cultures of adult mouse bone marrow, and all the main categories of hematopoietic cell precursors, hematopoietic stem cells among others, are identified. Such cultures are characterized by the formation of an adherent cell layer (ACL) of a complex composition containing fibroblastoid cells, giant adipocytes, endothelial cells, and macrophages. The ACL acts as the hematopoietic microenvironment necessary for support of proliferation and differentiation of the hematopoietic cells. It is natural, therefore, to assume that the microenvironment is created by the same precursors as in culture and in vivo, i.e., MSCs capable of transferring the hematopoietic environment and creating ectopic hematopoietic foci upon transplantation.
The transplantation of ACLs from 3–4-week-old cultures of syngeneic animals led to the creation of ectopic foci with the size of the foci formed from a fresh bone marrow plug (5–15x106 nucleated cells). Hematopoietic cells of all differentiation lineages were seen in the foci. The relative CFU-S content was the same as that in the bone marrow (11.4±3.4 per 105 cells) and did not differ from that in the foci produced from bone marrow plug [12]. Thus, cultivation in the long-term culture did not affect stromal precursor dramatically.
The importance of intercellular contacts for appropriate MSC function
Importantly, the bone marrow plug (or cells from long-term bone marrow culture) should be implanted under the renal capsule as a whole, while carefully avoiding converting it into a suspension. Implantation of cells as a suspension under the renal capsule means that no ectopic hematopoietic foci form [13] (for example with cells from long-term bone marrow cultures see Table 1).
Table 1. Transfer of hematopoietic microenvironment via cultures of bone marrow either in fragments or in cell suspension
№ of experiment | Method of implantation | Culture age, weeks | Number of cultures implanted | Foci size, x106 cells |
|---|---|---|---|---|
1 | Suspension | 7 | 4 | 0 |
2 | Suspension | 5 | 2 | 0 |
Fragments | 5 | 2 | 9.3 | |
3 | Suspension | 4 | 2 | 0 |
Fragments | 4 | 2 | 8.0 |
Simultaneous i.v. injection of bone marrow cells to donors did not affect the size of the foci formed from either irradiated donors, or donors with previously curetted bone marrow; meaning that mesenchymal stem cell (MSCs) numbers in the femurs were not affected by the injected cells [14].
One of the most important factors providing for the formation of a full-grown hematopoietic microenvironment in vitro is the explantation of the BM as a whole, or in fragments, but not as a suspension [8]. When the BM is seeded as a suspension, cells do not form the complex stromal layer; on the contrary, cells form a thin monolayer with fibroblast colonies. No hematopoiesis is observed in such layers. Therefore the dissociation of bone marrow cells changes their differentiation potential. Stromal progenitors do not fulfill the variety of cellular differentiations leading to the formation of complex structures of a hematopoietic microenvironment in culture. Thus, the intercellular connections are of most importance for the preserving of the MSC’s features.
When explanted in fragments, bone marrow stromal cells, initially occupying a tiny part of the cultivation flask, built hematopoietic stromal structures on the whole flask surface. During this process they do not lose (or constantly renew) essential intercellular contacts. In order to find out whether this ability is present in the cells from a completely formed cell layer a “wound” was inflicted on the 3-week-old ACL. One week later fibroblastoid cells were observed only rarely on the wound site. No complex ACL was formed. Completely different results were obtained when the “wound” was inflicted on a 1-week-old cell layer, it being in the formation process. One week later the wound site was covered with typical for ACL stromal cells so tightly that it was hardly definable. The ACL regenerated not only morphologically but also functionally as was demonstrated by the ectopic foci formation (Table 2).
Table 2. Size of the foci formed by intact 3-week-old or regenerated ACL (ACL was wounded after 1 week of cultivation)
ACL | Number of cultures | Foci size, x106 cells |
|---|---|---|
Intact part | 4 | 3.8 |
Regenerated part | 4 | 1.2 |
Thus, the intercellular contacts are of highest importance for the stromal progenitors’ differentiation during the processes of building the hematopoietic microenvironment. Stromal progenitor cells are able to keep the intercellular contacts while forming the microenvironment in vitro, and lose this ability when the functional adherent cell layer is formed [13].
The origin of stromal and hematopoietic cells in chimeras and the ectopic foci
Discriminant analysis showed that only MSCs of recipient origin are present in chimera bone marrow 6 and 12 months after irradiation and injection of hematopoietic cells (3–5x106) (Table 3).
Table 3. Discriminant analysis of hemopoietic stromal progenitor origin in B6-in-CBF chimeras
Time after irradiation, months | Number of chimeras tested | Recipient of implanted chimeric bone marrow | Foci formed/number of implants |
|---|---|---|---|
6 | 3 | B6 | 0/2 |
CBF | 4/4 | ||
12 | 18 | B6 | 0/16 |
CBF | 20/20 |
Chimera marrow implanted to non-irradiated mice of the donor strain (B6) was always rejected, and the hematopoietic microenvironment could only be transferred to the recipient strain (CBF) [14]. This means, firstly, that stromal cells in the ectopic hematopoietic foci are of BM donor origin, and secondly, that BM stromal cells injected intravenously for the reconstitution of hematopoiesis after irradiation did not engraft bone marrow stroma of chimeras.
The hematopoietic cells in the ectopic foci were only of recipient origin, as was shown after implantation of adherent cells from B6 female bone marrow cultures under the renal capsule of B6 males (Table 4). The origin of hematopoietic cells in the focus was determined according to the presence or absence of a Y-chromosome [11].
Table 4. The origin of hematopoietic cells in ectopic hemopoietic foci produced by adherent cell layer from long-term bone marrow culture
Donor | Recipient | Cells per focus, x106 | Donor/recipient metaphases | Foci formed/number of implants |
|---|---|---|---|---|
B6 female | B6 male | 24.4 | 0/100 | 2/2 |
B6 female | B6 male | 15.7 | 0/45 | 1/2 |
B6 female | B6 male | 10.4 | 0/40 | 1/2 |
B6 female | B6 male | 13.5 | 0/60 | 1/2 |
B6 female | B6 male | 5.8 | 0/7 | 1/2 |
The results show that stromal progenitors capable of hematopoietic microenvironment transfer cannot be transplanted i.v., and do not take part in MSC regeneration after irradiation. On implantation of BM of intact mice or adherent cell layer from bone marrow cultures under the renal capsule, ectopic hematopoietic foci form, in which the hematopoietic cells belong to the recipient while the stroma is of donor origin.
In order to investigate the origin of stromal cells in ACL, LTBMCs had been established from B6-in-CBF1chimeras, and when stable ACLs had been formed they were carefully scraped as a whole and implanted under the renal capsule in both B6 and CBF1 recipients. This discriminant analysis showed that ACL implantation produced ectopic foci only in the recipient line (CBF1) (Table 5).
Table 5. Discriminant analysis of hematopoietic stromal progenitors originating in adherent cell layer (ACL) of long-term bone marrow cultures of B6-in-CBF1 chimeras
Time after irradiation, months | Number of chimeras tested | Recipient of implanted ACL | Foci formed/number of implants |
|---|---|---|---|
12 | 4 | B6 | 0/4 |
CBF1 | 4/4 |
Thus, MSCs in the ACLs from long-term bone marrow cultures of chimeras are only of recipient origin [14].
Linear interdependency between the foci size and amount of MSCs implanted
Various amounts of medullary tissue ranging from 1/4 to 4 femoral bone marrow plugs were transplanted and the hematopoietic cells were counted in the foci formed 1 month later. The results are shown in Table 6, where it can be seen that despite the small number of implants (3–7), the number of nucleated cells on the whole showed a linear relation with the size of the implanted bone marrow fragment. The correlation coefficient (r) was 0.97±0.014 and the extrapolation number 4.68x10-5 [5].
Table 6. The influence of ectopic marrow implant size on hematopoietic cell number in the foci formed
Experiment № | Size of implant (femoral marrow plug equivalent) | Number of implants | Hematopoietic cells/focus (x106) |
|---|---|---|---|
1 | ¼ | 5 | 2.5 |
1 | 5 | 4.7 | |
2 | ¼ | 5 | 2.6 |
½ | 7 | 3.4 | |
1 | 6 | 10.0 | |
3 | ¼ | 3 | 3.8 |
1 | 4 | 8.1 | |
4 | 1 | 5 | 16.5 |
2 | 4 | 30.3 | |
4 | 3 | 68.0 | |
5 | ¼ | 3 | 68.0 |
½ | 10 | 7.9 | |
1 | 9 | 9.8 |
In summary, stromal cells implanted under the renal capsule of syngeneic animal form a hematopoietic microenvironment only if MSCs are preserved among them, and the size of these hematopoietic foci depends solely on the number of MSC among implanted stromal cells. These results allow MSC to be studied on this model.
The size of ectopic foci is proportional to the amount of ACL implanted. ACL taken from the half of the flask bottom produces a focus that is approximately half that formed by ACL collected from the whole surface of the culture flask: 35.6x106 and 58.1x106 nucleated cells, respectively (correlation coefficient is 0.996±0.005) [12].
When transplanted under the renal capsule of a syngeneic recipient, ACL of cultures of a single femur creates a focus approximately the size of a focus formed in implantation of bone marrow freshly isolated from a single femur. This coincidence suggests that the content of stroma precursors in the culture corresponds to the explanted bone marrow dose but not to other factors, for instance, the surface of the flask bottom. In view of this, the size of foci produced by ACL from 4–6-week-old cultures of 1/2, 1 and 2 femurs was studied (Table 7).
Table 7. Correlation between bone marrow dose plated in LTBMC and the size of the ectopic foci formed
Bone marrow plated per flask (femur equivalent) | Foci formed/Number of implants | Ectopic foci size, x106 cells |
|---|---|---|
½ | 5/7 | 1.7 |
1 | 10/13 | 4 |
2 | 9/10 | 8.3 |
The size of the foci was linearly associated with the dose of the implanted bone marrow (correlation coefficient 0.999±0.001) [12].
Kinetics of stromal precursor cell proliferation in vitro and during ectopic foci formation
The time-course of the stromal precursor repopulation during the process of a creating a site of ectopic hematopoiesis was also studied. In the first 6 hrs after implantation the number of transplantable stromal precursors reduced appreciably, reaching the nadir by the end of the first day (about 20% of the number implanted). Thereafter, there was a phase of regeneration and stromal precursors recovered up to the initial level in 3 weeks. The sensitivity of the stromal precursors to the cytostatics is in good agreement with such kinetics. Normally the stromal precursors do not actually show proliferative activity, which is seen from their insensitivity to MTX. Twenty-four hours after implantation their proliferative activity remains low. During the next 24 hrs the precursors are triggered into the cell cycle synchronously. At this time up to two-thirds of the stromal precursors are killed by the cytostatics. High sensitivity to the cytostatics is observed at 3–4 and 9–10 days after implantation, but not 5–6 days after. It is not clear whether these fluctuations are incidental, or if they are related to the movement of the partially synchronized cell population through the cell cycle. Three weeks later, i.e., when the number of stromal precursors had recovered, their proliferative activity decreased to the initial low level, and remained on that level [15].
Stromal precursors also proliferate during the formation of the adherent cell layer in the LTBMC. Considering the fact that hydroxyurea affects precursors from day 2 until day 11, it seems that these cells change their proliferative status slowly, for more than 24 hours. Thus, both the implantation of BM in vivo, leading to the building of a new hematopoietic microenvironment and hematopoietic foci formation, and the explantation of BM in vitro, leading to the building of a hematopoietic microenvironment in the form of an adherent cell layer in LTBMC, are accompanied by identical changes in the proliferative status of stromal precursors. In the first 24 hours after the transfer they remain at mitotic rest, then, during the next 2 days they mobilize into the cell cycle substantially and synchronically. For the next 2 weeks they are highly active in proliferation. Afterwards, despite continuous growth of ectopic foci or ACLs, the stromal precursors do not proliferate. This is reflected in the absence of increase in the number of stromal precursors both in vivo and in vitro after 3 weeks of formation of the microenvironment.
Characteristics of stromal progenitors in vivo and in vitro
De novo formation of a stromal microenvironment after the implantation of MSC under the renal capsule
In bone marrow implantation the hematopoietic cells leave the graft, whereas the stromal precursors form a new hematopoietic stroma, which is then repopulated by host cells. The cellularity of the hematopoietic focus is proportional to the initial implant size, i.e., to the content of the stromal precursors in it. On retransplantation of the intact ectopic site, hemopoietic cells again leave the implant, as they do after the primary implantation of the bone marrow plug. Twenty-four hours after retransplantation no more than about 3% of the CFU-S remain in the focus (Table 8) [15].
Table 8. Cellularity and CFU-S content of an ectopic site of hematopoiesis as a function of time after retransplantation
Time after retransplantation, days | Number of implants | Cellularity of ectopic foci, x106 | CFU-S per ectopic foci |
|---|---|---|---|
Before | 5 | 12.1 | 3842±545 |
1 | 6 | 3.3 | 107±16 |
4 | 6 | 1.8 | 148±18 |
7 | 5 | 4.5 | 641±90 |
10 | 6 | 7.9 | 1501±329 |
The replacement of the hematopoietic cells by the recipient cells in the retransplanted focus was also confirmed karyologically [16]. Hence, it appears that when the formed site of ectopic hematopoiesis is retransplanted, the hematopoietic microenvironment is created de novo.
Self-renewal ability of MSC
The results permitted the study of the capacity of MSCs for repeated formation of ectopic foci. Nine passages failed to produce any reduction in size of the newly formed hematopoietic foci (Table 9).
Table 9. Cellularity of ectopic bone marrow foci on repeated transplantation
Transfer number | Cells in the foci, x106 |
|---|---|
1 | 12.5 |
2 | 17.2 |
3 | 20.6 |
4 | 21.3 |
5 | 22.9 |
6 | 19.8 |
7 | 35.2 |
8 | 24.7 |
9 | 11.5 |
During the serial transfer of the ectopic hematopoietic tissue without ossicles, a complete loss of the ability to form the hematopoietic focus was already apparent at the third passage. In this case no more than half of the stromal precursors remained on the ossicle (when the bone marrow is pressed out of the femur only 10–15% of the stroma precursors remain on the bone), which was verified by separate implantation of the ossicle and hematopoietic tissue from focus [15].
The self-maintenance ability of the stromal precursors was also studied in a model in which the medullary cavity was repeatedly curetted. Four successive curettages were carried out, and in each over 90% of the stromal precursors were washed out of the femur. After each curettage, the complement of stromal precursors recovered over 1–1.5 months up to 50–60% of the initial and after the fourth curettage up to 20%. Subsequent curettages proved impossible because the whole medullary cavity was filled with newly formed bone [15].
The capacity for self-maintenance of stromal precursors from cultures was studied by repeated transfer of ectopic hemopoietic foci created by them in intermediate to final recipients (Table 10).
Table 10. Self-maintenance ability of hematopoietic stromal precursors from long-term bone marrow cultures
Experiment № | Intermediate recipients | Final recipients | ||
|---|---|---|---|---|
Foci/number of implants | Cellularity, x106 | Foci/number of implants | Cellularity, x106 | |
1 | 4/4 | 12.1 | 4/4 | 1.8 |
2 | 3/4 | 2.9 | 3/3 | 0.6 |
The self-maintenance of MSCs from LTBMC proved to be low and the size of the secondary foci was 10–15% of that of foci in the intermediate recipients [11]. Thus, MSCs are maintained in LTBMC and are capable of creating a hematopoietic microenvironment on transplantation. However, self-maintenance of these precursors from LTBMC is essentially diminished.
The data obtained have demonstrated a high ability of self-maintenance of the cells transferring the hematopoietic microenvironment. Twenty-four hours after BM implantation about 10% of the stromal precursors survive. The population of the precursors in the femur is reduced to approximately the same degree after bone marrow curettage. During regeneration the stromal precursors increase to 60–100% of the initial level, hence they must undergo three or four mitoses. This is consistent with the rise in their sensitivity to S-phase specific cytostatics for the first 2 weeks after implantation. Taking into consideration that on the serial transfer of hematopoietic tissue without ossicles or on serial curettage three or four cycles of regeneration are possible, the stromal precursors are able to undergo no less than 10–12 mitoses. This value is rather underestimated since calculating the loss of precursors for differentiation was not taken into account. The high self-maintenance ability, on the one hand, and the ability to form a fully differentiated bone marrow stromal tissue on the other, suggests that the cells transferring the hematopoietic microenvironment are true mesenchymal stem cells.
Radiosensitivity of MSCs
The hematopoietic stroma function of the femoral bone marrow exposed in vitro to 500 to 2700 rad of γ-rays was also studied, using the ectopic foci formation method. Irradiation of bones with 500 rad caused no noticeable damage to the MSCs’ ability to form a hematopoietic microenvironment. Higher doses produced an exponential decrease in MSCs. The D0 estimated from linear regression (regression equation: log survival=-0.000977x+0.7200) of this portion of the curve is 444±5 rad and the extrapolation number (n) is 5.2. The results for in vitro neutron irradiation of bone marrow agreed (regression equation: log survival=-0.002697x+0.1506). A small shoulder was evident followed by an exponential survival having D0 and n of 161±19 rad and 1.4, respectively [5].
The radiosensitivity of MSCs from 5-week-old LTBMC seemed very similar to that of non-cultivated ones (regression equation: log survival=-0.089x+0.3744; D0 was 486±15 rad and n was 2.4) [17].
When high doses of irradiation were used, implantation proved unsuccessful in some cases and no ossicles with hematopoiesis were formed. One may assume that not a single MSC is preserved in such implants. The independent and random character of radiation damage of cells suggests that the existence or nonexistence of MSCs in the implant is governed by Poisson’s distribution. In this case the data on the proportion of transplant failures (P0) allow the mean MSC content in the implant (x) to be calculated using the equation x=- ln P0. The total MSC content in the femoral bone marrow can be found by taking into account the fraction that survived exposure to the given dose. These data are shown in Table 11 [5] where it is seen that the results were quite consistent on the whole.
Table 11. The effect of g irradiation on the hematopoietic microenvironment transferring MSCs in murine femoral bone marrow
Irradiation dose, rad | Implant failure/total number of implants | MSC/implant (- ln P0) | Survival fraction | MSC per femur |
|---|---|---|---|---|
2100 | 6/22 | 1.3 | 0.033 | 39.9 |
2200 | 12/20 | 0.511 | 0.025 | 20.3 |
2200 | 9/21 | 0.847 | 0.013 | 65.4 |
2500 | 7/19 | 0.999 | 0.012 | 86.3 |
2700 | 17/20 | 0.163 | 0.007 | 23.3 |
2700 | 15/19 | 0.236 | 0.003 | 78.7 |
The mean number of MSCs calculated from the proportion of transplant failures after high doses of irradiation was 52.3±11.6 per femoral bone marrow plug.
The results show that MSCs are much more radioresistant than hematopoietic stem cells, for which D0 is about 100 rad. The second feature of MSCs is their marked capability to recover from sublethal γ-ray damage, which is characterized by a extrapolation number (5.2). In the case of neutron irradiation the extrapolation number is 1.4, which is evidence that MSCs are incapable of recovery from sublethal neutron-induced damage [5].
Despite their high radioresistance MSCs were still sensitive to irradiation. After lethal irradiation and syngeneic bone marrow transplantation of CBF1 mice, the MSCs were reduced to 1/5 of the initial level and slowly regenerated to subnormal level in 6 months. The number of bone marrow cells used for reconstitution of the primary recipient did not affect MSC regeneration (Table 12) [14].
Table 12. Hematopoietic stromal precursors in lethally irradiated CBF1 mice reconstituted with different doses of syngeneic bone marrow cells
Chimera’s characteristics | Ectopic hemopoietic foci produced by femoral marrow plug implantation from reconstituted mice | |||
|---|---|---|---|---|
Cell injected | Time after reconstitution, months | Foci formed/number of implants | Foci cellularity, x106 | Ossicle weight, mg |
2x105 | 2 | 8/8 | 4.0 | 1.4 |
7.4x107 | 2 | 8/8 | 4.8 | 1.4 |
2x105 | 6 | 8/8 | 5.5 | 2.0 |
7.4x107 | 6 | 8/8 | 5.4 | 2.1 |
control | -- | 12/12 | 10.7 | 1.6 |
Two to six months after irradiation, the content of stromal progenitors in the mouse femur was, judging from the cellularity of the foci produced by them, 40–50% of the initial level in both groups of mice reconstituted both in minimal protective dose of marrow cells (2x105) and with a hundredfold dose. Thus, MSCs could be affected by high doses of irradiation and in such cases they are not able to regenerate completely.
Influence of the quality of hematopoiesis on MSCs’ proliferative potential
MSCs were compared in chimeras and double chimeras. Hematopoietic foci formed in standard recipients via BM from chimeras were approximately 2 times smaller when compared with foci formed from BM of non-irradiated mice, and 2 times bigger compared to foci formed from BM from double chimeras. These data confirm that stromal precursors are radiosensitive and unable to recover from radiation damage completely. Interestingly, secondary and tertiary chimeras’ BM formed the same small ectopic foci as double chimeras did, while the dose of irradiation affected the stroma of secondary and tertiary chimeras was 2 times lower than of double chimeras [18]. When BM from all types of chimeras tested were explanted in LTBMC, and after 3–4 weeks of cultivation were implanted under the renal capsule of syngeneic mice, foci formed from ACLs from chimeras’ BM were 75%, foci formed from ACLs from double chimeras’ BM were 20%, and ACLs from secondary and tertiary chimeras were approximately 40% by size from ACLs from non-irradiated mice. The secondary and tertiary chimeras’ stromal precursors were irradiated only once while hematopoietic cells had undergone 2 or 3 rounds of intensive proliferation during reconstitution of hematopoiesis. Thus, judging by the grade of irradiation damage, stromal cells from secondary and tertiary chimeras were similar to ordinary chimeras. Nevertheless, secondary and tertiary chimeras’ stromal precursors turned out to be affected more deeply than the same cells in ordinary chimeras. The data indicates that the stroma’s damage was determined not only by the irradiation dosage but by the quality of hematopoietic cells proliferating on it [18].
Hierarchical organization of the MSC compartment: existence of more mature than MSC-inducible precursor cells
In BM implantation, the ectopic hemopoietic focus is larger in an irradiated recipient than in a non-irradiated one in a dose-dependent manner (Table 13) [19].
Table 13. The size of the ectopic foci in irradiated recipients
Dose of irradiation | Foci size, % of control |
|---|---|
0 | 100 ± 18.8 |
1.5-2.5 | 156 ± 20 |
4.0-6.0 | 200 ± 37.5 |
7.0-8.0 | 210 ± 31.2 |
10.0-13.0 | 290 ± 68.7 |
In subsequent passages the size of the focus did not increase further (Table 14, compare with Table 9).
Table 14. Cellularity of ectopic bone marrow foci on repeated transplantation into irradiated recipients
Transfer number | Cells in the foci, x106 |
|---|---|
1 | 15.9 |
2 | 18.1 |
3 | 31.0 |
4 | 18.2 |
5 | 38.4 |
6 | 28.4 |
7 | 35.2 |
8 | 20.1 |
Hence, one may conclude that in the irradiated recipient the number of stromal precursors in an ectopic focus does not correspond to the large size of the focus. This was demonstrated more directly by implantation of similar bone marrow fragments into non-irradiated and irradiated (chimeric) recipients, subsequently testing the content of the stromal precursors in the sites formed by their retransplantation to non-irradiated recipients. In these experiments the primary focus formed in chimeras exceeded that in the non-irradiated ones by a factor of 2.2 (27.3x106 and 12.5x106). The content of the stromal precursors in both was essentially the same since the cellularities of the foci formed on transfer to the non-irradiated recipients were 10.93x106 and 11.83x106, respectively [15]. Stromal precursors from a culture also react to stimulation from the irradiated recipient, the response being much stronger than in implantation of freshly isolated bone marrow: the foci were 5–7 times larger in the irradiated recipients than in the non-irradiated ones (35.1±8x106 versus 5.3±1.2x106) (Table 15) [11].
Table 15. Size of ectopic foci produced by adherent cell layer from LTBMC in non-irradiated and irradiated recipients
Experiment № | Culture age, weeks | Non-irradiated recipients | Irradiated recipients | ||
|---|---|---|---|---|---|
| Foci formed/number of implants | Cellularity, x106 | Cellularity, x106 | Cellularity, x106 | |
1 | 2 | 2/2 | 0.7 | 2/2 | 22.5 |
2 | 4 | 0/2 | -- | 2/2 | 30.5 |
3 | 4 | 2/2 | 8.0 | 1/2 | 7.6 |
4 | 4 | 2/2 | 5.7 | 2/2 | 35.5 |
5 | 5 | 2/2 | 9.3 | 2/2 | 55.0 |
6 | 6 | 6/6 | 2.9 | 2/2 | 105.0 |
7 | 9 | 4/4 | 4.8 | 4/4 | 12.5 |
Similar results were obtained when LTBMC were established from different amounts of bone marrow (1/2, 1, 2 femurs). All cultures proved to be alike in hematopoiesis maintenance, though the MSC content in them corresponded to the dose of plated bone marrow (see Table 7). At the same time, in irradiated recipients all cultures produced foci approximately the same size (37.1, 42.7 and 38.3x106 correspondingly) [12].
The effect of hydroxyurea was estimated by the size of ectopic foci formed from treated ACLs in irradiated and non-irradiated recipients [20]. The results were similar in both types of recipients. So one may conclude that during the ACL formation both types of stromal precursors actively proliferate. MSCs functioning during the transfer into non-irradiated recipients and the more mature precursors taking part in the foci formation in the irradiated recipients.
The data suggest that the compartment of the hemopoietic stromal precursors is heterogenic and includes cells of at least two differentiation levels. Those less differentiated, MSCs able to transfer a hematopoietic microenvironment are marked by a relatively high self-maintenance, do not respond to the systemic demand of the irradiated recipient, and create a microenvironment, the size of which is proportional to the number of transferred MSCs. More mature precursors are marked by poor self-maintenance; they respond to the systemic demand of the irradiated recipient and, in the culture, to the surface of the flask bottom, and are not transplantable via in vivo transfer.
Summarizing the data presented above, the compartment of stromal bone marrow cells has a hierarchical structure. There are true mesenchymal stem cells (MSCs) capable of both self-maintaining and differentiating into all stromal lineages, and more mature inducible stromal precursors, which keep the ability for multipotential differentiations while losing their self-renewing ability. MSCs are mainly in mitotic rest and are not sensitive to the systemic demand, while more mature precursors proliferate more easily in the case of systemic requirements.
More mature inducible stromal precursors are sensitive to the unknown factor(s) released after irradiation. When injected during foci formation sera from irradiated mice also stimulate these precursors, resulting in increased size of the foci formed – the size of the foci was 19.5±1. 8x106 compared with 14±1.5x106 in control mice [19]. Addition of sera from irradiated mice to the LTBMC also increases the number of stromal cells in the ACLs (Table 16) [21].
Table 16. Influence of the sera from irradiated mice on the number of cells in the ACLs from LTMBC
Group | Cell number per well, х 103 |
|---|---|
control (no additional serum) | 118 ± 4 |
2% of sera from non-irradiated mice | 131 ± 7 |
0.5% of sera from irradiated mice | 160 ± 4 |
1 % of sera from irradiated mice | 185 ± 5 |
2 % of sera from irradiated mice | 206 ± 5 |
In order to define the organ producing the unknown factor(s), various organs of irradiated mice were co-transplanted simultaneously with the implantation of the BM plug under the renal capsule. Intravenous injection of irradiated sera as well as implantation of 5–6 irradiated bones under the skin enhanced the growth of stromal cells in the foci formed (Table 17) [21].
Table 17. Analysis of the various organs of irradiated mice for their stroma-stimulating activity
Recipients | The organ from irradiated mice, transplantation site | Foci size, х 106 |
|---|---|---|
intact (non-irradiated) | 9.0 ± 1.7 | |
irradiated | 21.1 ± 6.2 | |
intact | BM from 6 femurs, under the skin | 8.6 ± 2.3 |
intact | 5–6 femurs, under the skin | 22.0 ± 4.1 |
intact | Thymus, under the renal capsule | 14.8 ± 3.4 |
intact | Equivalent of ½ of the spleen, intravenously | 10.5 ± 1.2 |
intact | 1/3 of the spleen, under the renal capsule | 11.8 ± 3.3 |
intact | the spleen, under the skin | 13.1 ± 2.8 |
intact | 1/3 of the liver, under the skin | 14.8 ± 3.2 |
intact | Sera from irradiated mice, intravenously | 20.1 ± 1.5 |
intact | Sera from non-irradiated mice, intravenously | 14.0 ± 2.8 |
Thus, the unknown factor(s) stimulating the growth of stromal inducible precursor cells are produced in the irradiated bones and secreted into the blood serum.
The regulation of MSCs in vivo by hematopoietic growth factors
Regulation of MSCs by soluble factors remains obscure. During the formation of the hematopoietic microenvironment MSCs are affected by G-CSF. When recipients of BM were injected over 10 or 17 days beginning from the day after implantation of BM under the renal capsule it dramatically decreased size of the foci formed (Table 18).
Table 18. Influence of G-CSF on the ectopic foci formation from the bone marrow of intact mice
G-CSF treatment | Bone marrow implantation | Foci retransplantation | ||||
|---|---|---|---|---|---|---|
Implant number | Cellularity, x106 | Ossicle weight, mg | Implant number | Cellularity, x106 | Ossicle weight, mg | |
Control | 4 | 8.3±1.7 | 2.2±0.4 | 4 | 16.2±3.3 | 2.3±0.5 |
10 days | 4 | 5.3±0.7 | 2.7±0.7 | 4 | 9.0±1.8 | 1.9±0.5 |
17 days | 6 | 3.4±0.6 | 2.0±0.4 | 6 | 1.7±0.3 | 1.3±0.4 |
Obviously, when administered during the active proliferation and differentiation of MSC, G-SCF inhibits their proliferation (judging from the decreased size of the foci formed); moreover, it diminishes the number of MSCs themselves as was shown by retransplantation of the foci [22].
Conversely, cytokine treatment of the MSCs in their steady-state (in the intact bone marrow increases the number of these stromal precursors (Table 19).
Table 19. Size of the ectopic foci formed from the bone marrow of mice treated with cytocines
Group | Bone marrow implantation | Foci retransplantation | ||||
|---|---|---|---|---|---|---|
Implant number | Cellularity, x106 | Ossicle weight, mg | Implant number | Cellularity, x106 | Ossicle weight, mg | |
Control | 9 | 6.5±1.0 | 2.0±0.2 | 4 | 5.9±1.2 | 2.6±0.4 |
G-CSF, 6 days | 4 | 7.4±2.2 | 1.1±0.2 | |||
G-CSF, 10 days | 3 | 10.7±2.0 | 1.0±0.2 | 3 | 11.3±2.9 | 3.0±0.6 |
G-CSF, 17 days | 4 | 9.2±1.0 | 3.3±0.7 | 3 | 13.3±2.8 | 3.5±0.7 |
G-CSF+SCF, 6 days | 4 | 6.4±1.6 | 2.2±0.5 | |||
G-CSF+SCF, 10 days | 4 | 12.8±1.5 | 2.4±0.6 | |||
G-CSF+SCF, 17 days | 4 | 18.4±3.9 | 1.7±0.5 | 5 | 19.5±4.2 | 3.2±0.6 |
The combination of G-CSF with SCF and the longest treatment (for 17 days) had a maximal effect on the MSC number in the bone marrow of treated mice. In the case of G-CSF treatment this effect was transient and did not last for a month, in the case of cytokine combination, however, the increase in the number of MSCs was stable for at least a month. Cytokine treatment did not affect the osteogenic potential of MSCs either during stroma formation or in the intact bone marrow [22].
Thus, during the building of ectopic hematopoietic foci when stromal precursors are proliferating and differentiating, pharmacological concentrations of G-CSF inhibit the process of foci formation and diminish the number of stromal precursors in them. When affecting the mature non-proliferating bone marrow stroma, cytokines increase the number of MSCs.
Conclusions
Summarizing the works of J. L. Chertkov, it is possible to describe the main features of MSCs. These cells are capable of transferring a hematopoietic microenvironment due to both their high proliferative potential and their ability to differentiate into all bone marrow stromal lineages, including bone, cartilage, and marrow stromal cells. MSCs are more radioresistant than HSCs but they still suffer from radiation and their damage could not be fully recovered. Impaired hematopoiesis also influences the MSCs. The compartment of MSCs and stromal precursor cells is organized hierarchically. Therefore, J. L. Chertkov described the main features of MSCs from many sides using the functional assay.
Acknowledgements
Irina Shipounova and Nina Drize for preparing the compilation of Chertkov’s works on hematopoietic stromal microenvironment.
Gurevich O. A., Udalov G. A., Samoylina N. L., Samoylova R. S., Lemeneva N. L., Todria T. V., Olovnikova N. I., Olshanskaya Y. V., Shiponova (Nifontova) I. N., Ershler M. A. and Drize N. I. as co-authors of his works.
References
3. Olovnikova NI, Drize NJ, Ershler MA, Nifontova IN, Belkina EV, Nikolaeva TN, Proskurina NV, Chertkov JL. Developmental fate of hematopoietic stem cells: the study of individual hematopoietic clones at the level of antigen-responsive B lymphocytes. Hematol J. 2003;4(2):146-150.
4. Drize NJ, Olshanskaya YV, Gerasimova LP, Manakova TE, Samoylina NL, Todria TV, Chertkov JL. Lifelong hematopoiesis in both reconstituted and sublethally irradiated mice is provided by multiple sequentially recruited stem cells. Exp Hematol. 2001;29(6):786-794.
5. Chertkov JL, Gurevitch OA. Radiosensitivity of progenitor cells of the hematopoietic microenvironment. Radiat Res. 1979;79(1):177-186.
6. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9(5):641-650.
7. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005;7(5):393-395.
8. Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977;91(3):335-344.
9. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6(2):230-247.
10. Udalov GA, Gurevich OA, Chertkov IL. Origin of hematopoietic cells in a syngenous and semisyngenous focus of heterotopic hematopoiesis. Biull Eksp Biol Med. 1977;83(5):584-586.
11. Chertkov JL, Drize NJ, Gurevitch OA, Udalov GA. Hemopoietic stromal precursors in long-term culture of bone marrow: I. Precursor characteristics, kinetics in culture, and dependence on quality of donor hemopoietic cells in chimeras. Exp Hematol. 1983;11(3):231-242.
12. Chertkov JL, Drize NJ, Gurevich OA. Hemopoietic microenvironment and hemopoietic stroma precursors. Recent advances in haematology immunology and blood transfusion : proceedings of the plenary sessions of the joint meeting of the 19th Congress of the International Society of Haematology and the 17th Congress of the International Society of Blood Transfusion, Budapest, August 1-7, 1982, Eds. Susan R. Hollán; International Society of Haematology, 12,1983;133-147.
13. Gurevich OA, Drize NI, Chertkov IL. Importance of cell contacts for the differentiation of the precursor cells of hematopoietic stroma in long-term bone marrow cultures. Biull Eksp Biol Med. 1982;94(8):97-100.
14. Chertkov JL, Drize NJ, Gurevitch OA, Samoylova RS. Origin of hemopoietic stromal progenitor cells in chimeras. Exp Hematol. 1985;13(11):1217-1222.
15. Chertkov JL, Gurevitch OA. Self-maintenance ability and kinetics of haemopoietic stroma precursors. Cell Tissue Kinet. 1980;13(5):535-541.
16. Chertkov JL, Gurevich OA, Udalov GA. Role of bone marrow stroma in the phenomenon of hybrid resistance. Biull Eksp Biol Med 1979 Apr; 87(4):337-40.
17. Gurevich OA, Chertkov JL. Radiosensitivity of hemopoietic stroma precursors from long-term bone marrow culture. Radiobiology. 1983;23(4):521-523.
18. Gurevich OA, Drize NI, Udalov GA, Chertkov IL. Effect of hematopoiesis on progenitor bone marrow stromal cells. Biull Eksp Biol Med. 1982;94(10):115-117.
19. Chertkov JL, Gurevitch OA. Hematopoietic stem cell and its microenvironment. Moscow, Meditzina 1984. Russian.
20. Gurevich OA, Drize NJ, Chertkov JL. Proliferation of cells-precursors of hematopoietic microenvironment in murine long-term bone marrow culture. Bull Exp Biol Med. 1984;XCVIII(11):612-614.
21. Drize NI, Ershler MA, Chertkov IL. Radiation-induced hemopoietic cell growth factor: detection in a culture. Bull Exp Biol Med. 2001;132(6):1213-1215.
22. Drize NJ, Chertkov JL. Influence of cytokine (G-CSF and SCF) treatment on the murine precursors of hematopoietic stroma. Bull Exp Biol Med. 1998;125(2):204-206.
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Introduction
Prof. J. L. Chertkov (1927–2009) devoted most of his efforts to understanding the mechanisms of hematopoiesis. He was interested in the developmental fate of hematopoietic stem cells (HSC), and the result of his investigations became the theory of clonal succession of HSC, which was published in several papers [1-4]. The data showed that long-term hematopoiesis is maintained by a large number of simultaneously functioning small, short-lived (1 to 3 months) clones that usually grow locally with little or no dispersion between different regions of the hematopoietic system. Only 10% of clones are long-lived and can function during the whole life of the animal. Furthermore, clones that disappear are never detected again. The data suggests that normal hematopoiesis is supported by the sequential recruitment of marrow repopulating cells into a differentiation mode.
In the mid 1970s, together with A. J. Friedenstein, Joseph Chertkov laid the foundation for experimentation into the differences between HSC and precursor cells in the hematopoietic microenvironment. He postulated that an understanding of the interrelationship between the stem cells of hematopoiesis and regulatory stromal microenvironment is necessary for an investigation of the process of hematopoiesis. To analyze the stromal precursor cells J. L. Chertkov used a functional assay where the microenvironment is addressed as the territory where hematopoiesis takes place and therefore could be estimated by the number of hematopoietic cells maintained on it. The method of ectopic hematopoietic foci formation provides a separate hematopoietic territory built de novo via special stromal precursor cells. Cells capable of transferring the hematopoietic microenvironment were referred to by Chertkov as hematopoietic microenvironment-transferring units (HMTU) [5].
In 1991 A. Caplan defined stem cells capable of giving rise to skeletal tissues – cartilage, bone, tendon, ligament, marrow stroma, and connective tissue – as mesenchymal stem cells (MSC) [6]. The term MSC was used in the fields of cytotherapy and tissue engineering widely and not always correctly; therefore the International Society of Cellular Therapy postulated the use of the term MSC only for cells that fulfilled the stem cell criteria: multipotentiality and self-renewal [7]. All works of Prof. Chertkov clearly demonstrate that HMTU and MSC are synonyms. Therefore we will use the term MSC for cells described by J. L. Chertkov as HMTU.
The compilation of the works by J. L. Chertkov characterizes MSCs both quantitatively and qualitatively, based on their functional properties. MSCs were shown to have a high proliferative potential, to be able to develop multilineage progeny, and form a fully functional hematopoietic microenvironment. The compartment of stromal precursor cells was shown to have a hierarchical structure, and inducible precursor cells were characterized. The radiosensitivity of MSCs and their progeny was estimated and it was then possible to calculate the direct number of MSC in the murine femur.
Materials and Methods
Mice
Female and male C57BL/6 (B6), CBA, CBAT6T6, (CBAxC57BL/6) F1 hybrid (CB), and (CBAT6T6xC57BL/6) F1 hybrid (CBT) mice 8–25 wks of age at the beginning of the study were used. Care was taken that the groups to be compared originated from the same batch of animals housed under the same conditions.
Irradiation of mice
In some of the experiments the recipient mice were irradiated with 400 or 700 rad from a 137Cs IPK irradiator 3 to 4 hrs before bone marrow (BM) implantation. Both doses produced the same effect on the size of the ectopic foci. The irradiator consisted of four 137Cs sources set in a quadrilateral arrangement about the site of exposure.
In order to obtain blood sera containing stroma-stimulating activity, the mice were irradiated with 6–12 Gy (in the latter case the protective dose of BM cells was injected i.v.).
Bone marrow irradiation
In the case of an in vivo irradiation the mice were irradiated and sacrificed immediately thereafter. The femurs were removed and stored on ice until transplantation. For in vitro irradiation the femurs were exposed either to γ-rays from an IPK irradiator with the absorbed dose rate of 500 rad/min or to fast neutrons generated by the Obninsk BR-10 research reactor. The mean energy of fast neutrons was 0.85MeV, the power of the tissue Kerma 128 rad/min, and the ratio of neutron to γ-ray doses at the point of exposure of the bones was approximately 20:1. The γ-ray component was ignored in calculating the dose-response curves, and all neutron doses represent the rad dose of the neutron component. In all experiments, the period between bone resection and the implantation of the bone marrow did not exceed 5 hrs. The sequence of implantation of femurs exposed to various doses was always randomized.
Chimeras
The mice were exposed to 12–13 Gy and reconstituted with syngeneic or allogeneic BM in doses indicated in the corresponding part of the text. In general, 1/3–1/4 of the femoral equivalent was injected (standard chimeras). Secondary chimeras were obtained when irradiated recipients were reconstituted with hematopoietic cells of standard chimeras; the cells were collected no earlier than 2 months after the creation of the standard chimeras. Tertiary chimeras were obtained when the irradiated recipients were reconstituted with hematopoietic cells of secondary chimeras; the cells were also collected no earlier than 2 months after the creation of the secondary chimeras. Double chimeras were obtained when the standard chimeras were exposed to a dose of 12–13 Gy 2–5 months after creation of the chimera, and reconstituted with hematopoietic cells of normal mice. The stromal precursors were studied 3–9 months after creation of the chimeras.
Bone marrow or adherent cell layer implantation
Implantation was performed under the renal capsule of anesthetized mice. The femurs were freed of muscle, the epiphyses cut away, and the bones stored on ice until used. The BM was pressed out of the femur with a stylet or thick needle with a blunt end. In anesthetized mice a small tear was made in the renal capsule and a bone marrow plug or adherent cell layer (ACL) from long-term bone marrow culture placed under it with a small spatula. The ACL was removed from the flask bottom with a rubber policeman and implanted under the renal capsule without conversion to a single-cell suspension. In cases of ectopic foci reimplantation the whole focus was removed from the kidney and implanted under the renal capsule of the recipient. In cases where suspended BM was implanted, the 0.5 ml of suspension (made by repeated passage through a 23-gauge needle) containing 1–2x107 cells was precipitated via centrifugation onto a Millipore HA filter (0.45 micron). The filter was folded so that the cells were inside it and then was transplanted under the renal capsule of the recipient mice. The size of the foci produced was determined after 1–1.5 months by counting the number of nucleated hematopoietic cells in them. The ossicle containing BM was removed from the kidney, and the cells were scraped off the bone with a scalpel into medium 199 or α-MEM and prepared as a single cell suspension by passing it repeatedly through a syringe fitted with a 21-gauge needle. In some experiments the cellularity of the foci was determined in the pool of all foci in each group; consequently, the standard error cannot be calculated. In general the error in such experiments was about 20%.
Bone marrow ablation
After anesthesia, a small incision was made over the knee joint, and the medullary cavity of the femur was entered and curetted using a dental root-canal broach. This was followed by the insertion of a 23-gauge needle into the medullary cavity of the curetted femur, which was then irrigated vigorously with 1 ml of medium 199.
Determination of the proliferative activity of stromal precursors in vivo
The S-phase specific cytostatic compound methotrexate (MTX) was injected intraperitoneally in a single dose of 0.25 mg/g. This dose of MTX was lethal and therefore 4 hrs after its injection the bone marrow or ectopic site was transferred into a normal recipient.
Long-term bone marrow culture
The marrow cells or the cells of an ectopic hematopoietic focus were cultivated by the method described by Dexter et al. [8]. The cells were flushed out with 10 ml of complete medium into a 25cm2 flask without converting them to a single-cell suspension. In the case of cultivation of suspended BM cells, 1 femur was suspended by repeated passage through a 21-gauge needle and then seeded onto the 25cm2 flask. When cultivated in a 24-well plate, 2 femurs were explanted per plate, also without conversion into a single-cell suspension. Fisher medium supplemented with L-glutamine, antibiotics (all Flow Labs), 25% serum (2:1, horse: fetal calf sera, Gibco and Flow Labs) and 10-6M hydrocortisone sodium hemisuccinate (Sigma) were used. The culture was kept at 330C and 5% of CO2 with weekly replacement of 50% of the medium.
The “wound” was performed by scraping 1/2of the adherent cell layer (ACL) with the rubber policeman.
Determination of the proliferative activity of stromal precursors in vitro
Hydroxyurea was added to a long-term bone marrow culture (LTBMC) at the concentration of 13mM (1mg/ml) for periods from 2 hr to 7 days. To stop the function of hydroxyurea the ACLs were washed 3 times with 5 ml of medium 199 with 2% of FCS.
Cytokine treatment
Cytokines (recombinant rat SCF (Amgen) and recombinant human G-CSF (Neupogen 48, Amgen)) were dissolved into the 0.9% NaCl solution with 0.1% of BSA and injected once a day under the skin for 6, 10, or 17 days. G-CSF was used at the concentration of 250 mkg/kg, and SCF at 34 mkg/kg. The control group was injected with 0.9% NaCl solution with 0.1% of BSA only. Twenty hours or 1 month after the last injection, BM from the femurs of the control and cytokine-treated mice was implanted under the renal capsule of the syngeneic mice. In order to define the effect of G-CSF on foci formation the mice were implanted with the syngeneic BM 1 day before beginning the G-CSF courses, which lasted 10 or 17 days.
Sera from irradiated mice
Blood was obtained from the femoral vein not earlier than 1 week after the irradiation. After the clot retraction sera were centrifuged (3000 rpm), supernatant was sterilized by filtration through 0.22 µm filters.
Analysis of various organs of irradiated mice for stroma-stimulating activity
Bone marrow, thymus, bones, liver, and spleen of irradiated mice were implanted into intact mice under the skin or renal capsule. Suspended spleen cells were injected intravenously to the mice previously treated with heparin (50 U/mouse). Intact BM was implanted simultaneously under the renal capsule of these mice.
Karyotype analysis
The origin of the hematopoietic cells in the focus was determined according to the presence or absence of Y-chromosomes, using the G-banding technique.
Histology
The kidneys were removed and fixed in Carnoy’s solution, decalcified, embedded in paraffin and cut into series of 5 µm sections. The preparations were stained with Pappenheim, Giemsa, and hematoxylin-eosin stains.
Statistics
The radiosensitivity curves were fitted to the data via linear regression analysis, from which the D0s, standard errors, and extrapolation numbers were calculated. The concentration of MSC in the femur was calculated using Poisson’s distribution. When not otherwise noted, the data were analyzed with Student’s t-test.
Results and Discussion
Methods of in vitro and in vivo mesenchymal stem cells analysis
In the case of bone marrow (BM) implantation under the renal capsule of the syngeneic animal, the hematopoietic cells leave the graft, whereas the stromal precursors form the new hematopoietic stroma, which is then repopulated by host cells [9, 10]. The same processes take place after implantation of an adherent cell layer from 3–4 wk bone marrow cultures. The beginning of vessel formation was evident by 12 h after implantation. The blood supply to the implant was established 24–48 h after implantation. Characteristic connective tissue lacunae form, and clusters of connective tissue cells were seen from day 4–5, as well as strands of fibroblasts and sometimes the beginning of cartilage development, which was replaced by osteogenesis. By day 6 the implant on the side toward the kidney contained many dead cells with pyknotic nuclei, many erythrocytes, and colonies of hemopoietic cells with blasts cells in the center. On the top and sides of the implant cancellous bone formation was observed. Within the foci there were individual osteoblasts in broad cavities with developing bone trabeculae around them. Osteogenesis was very intensive and 1–2 days later large areas of de novo formed bone could be observed. After 11 days, the typical bone marrow structures such as sinusoids, adipocytes, and areas of hemopoietic cells of different lines of differentiation were represented, and by the end of the second week a well-developed ectopic hemopoietic foci was created [11].
Polymorphic hemopoiesis is maintained for many weeks in long-term cultures of adult mouse bone marrow, and all the main categories of hematopoietic cell precursors, hematopoietic stem cells among others, are identified. Such cultures are characterized by the formation of an adherent cell layer (ACL) of a complex composition containing fibroblastoid cells, giant adipocytes, endothelial cells, and macrophages. The ACL acts as the hematopoietic microenvironment necessary for support of proliferation and differentiation of the hematopoietic cells. It is natural, therefore, to assume that the microenvironment is created by the same precursors as in culture and in vivo, i.e., MSCs capable of transferring the hematopoietic environment and creating ectopic hematopoietic foci upon transplantation.
The transplantation of ACLs from 3–4-week-old cultures of syngeneic animals led to the creation of ectopic foci with the size of the foci formed from a fresh bone marrow plug (5–15x106 nucleated cells). Hematopoietic cells of all differentiation lineages were seen in the foci. The relative CFU-S content was the same as that in the bone marrow (11.4±3.4 per 105 cells) and did not differ from that in the foci produced from bone marrow plug [12]. Thus, cultivation in the long-term culture did not affect stromal precursor dramatically.
The importance of intercellular contacts for appropriate MSC function
Importantly, the bone marrow plug (or cells from long-term bone marrow culture) should be implanted under the renal capsule as a whole, while carefully avoiding converting it into a suspension. Implantation of cells as a suspension under the renal capsule means that no ectopic hematopoietic foci form [13] (for example with cells from long-term bone marrow cultures see Table 1).
Table 1. Transfer of hematopoietic microenvironment via cultures of bone marrow either in fragments or in cell suspension
№ of experiment | Method of implantation | Culture age, weeks | Number of cultures implanted | Foci size, x106 cells |
|---|---|---|---|---|
1 | Suspension | 7 | 4 | 0 |
2 | Suspension | 5 | 2 | 0 |
Fragments | 5 | 2 | 9.3 | |
3 | Suspension | 4 | 2 | 0 |
Fragments | 4 | 2 | 8.0 |
Simultaneous i.v. injection of bone marrow cells to donors did not affect the size of the foci formed from either irradiated donors, or donors with previously curetted bone marrow; meaning that mesenchymal stem cell (MSCs) numbers in the femurs were not affected by the injected cells [14].
One of the most important factors providing for the formation of a full-grown hematopoietic microenvironment in vitro is the explantation of the BM as a whole, or in fragments, but not as a suspension [8]. When the BM is seeded as a suspension, cells do not form the complex stromal layer; on the contrary, cells form a thin monolayer with fibroblast colonies. No hematopoiesis is observed in such layers. Therefore the dissociation of bone marrow cells changes their differentiation potential. Stromal progenitors do not fulfill the variety of cellular differentiations leading to the formation of complex structures of a hematopoietic microenvironment in culture. Thus, the intercellular connections are of most importance for the preserving of the MSC’s features.
When explanted in fragments, bone marrow stromal cells, initially occupying a tiny part of the cultivation flask, built hematopoietic stromal structures on the whole flask surface. During this process they do not lose (or constantly renew) essential intercellular contacts. In order to find out whether this ability is present in the cells from a completely formed cell layer a “wound” was inflicted on the 3-week-old ACL. One week later fibroblastoid cells were observed only rarely on the wound site. No complex ACL was formed. Completely different results were obtained when the “wound” was inflicted on a 1-week-old cell layer, it being in the formation process. One week later the wound site was covered with typical for ACL stromal cells so tightly that it was hardly definable. The ACL regenerated not only morphologically but also functionally as was demonstrated by the ectopic foci formation (Table 2).
Table 2. Size of the foci formed by intact 3-week-old or regenerated ACL (ACL was wounded after 1 week of cultivation)
ACL | Number of cultures | Foci size, x106 cells |
|---|---|---|
Intact part | 4 | 3.8 |
Regenerated part | 4 | 1.2 |
Thus, the intercellular contacts are of highest importance for the stromal progenitors’ differentiation during the processes of building the hematopoietic microenvironment. Stromal progenitor cells are able to keep the intercellular contacts while forming the microenvironment in vitro, and lose this ability when the functional adherent cell layer is formed [13].
The origin of stromal and hematopoietic cells in chimeras and the ectopic foci
Discriminant analysis showed that only MSCs of recipient origin are present in chimera bone marrow 6 and 12 months after irradiation and injection of hematopoietic cells (3–5x106) (Table 3).
Table 3. Discriminant analysis of hemopoietic stromal progenitor origin in B6-in-CBF chimeras
Time after irradiation, months | Number of chimeras tested | Recipient of implanted chimeric bone marrow | Foci formed/number of implants |
|---|---|---|---|
6 | 3 | B6 | 0/2 |
CBF | 4/4 | ||
12 | 18 | B6 | 0/16 |
CBF | 20/20 |
Chimera marrow implanted to non-irradiated mice of the donor strain (B6) was always rejected, and the hematopoietic microenvironment could only be transferred to the recipient strain (CBF) [14]. This means, firstly, that stromal cells in the ectopic hematopoietic foci are of BM donor origin, and secondly, that BM stromal cells injected intravenously for the reconstitution of hematopoiesis after irradiation did not engraft bone marrow stroma of chimeras.
The hematopoietic cells in the ectopic foci were only of recipient origin, as was shown after implantation of adherent cells from B6 female bone marrow cultures under the renal capsule of B6 males (Table 4). The origin of hematopoietic cells in the focus was determined according to the presence or absence of a Y-chromosome [11].
Table 4. The origin of hematopoietic cells in ectopic hemopoietic foci produced by adherent cell layer from long-term bone marrow culture
Donor | Recipient | Cells per focus, x106 | Donor/recipient metaphases | Foci formed/number of implants |
|---|---|---|---|---|
B6 female | B6 male | 24.4 | 0/100 | 2/2 |
B6 female | B6 male | 15.7 | 0/45 | 1/2 |
B6 female | B6 male | 10.4 | 0/40 | 1/2 |
B6 female | B6 male | 13.5 | 0/60 | 1/2 |
B6 female | B6 male | 5.8 | 0/7 | 1/2 |
The results show that stromal progenitors capable of hematopoietic microenvironment transfer cannot be transplanted i.v., and do not take part in MSC regeneration after irradiation. On implantation of BM of intact mice or adherent cell layer from bone marrow cultures under the renal capsule, ectopic hematopoietic foci form, in which the hematopoietic cells belong to the recipient while the stroma is of donor origin.
In order to investigate the origin of stromal cells in ACL, LTBMCs had been established from B6-in-CBF1chimeras, and when stable ACLs had been formed they were carefully scraped as a whole and implanted under the renal capsule in both B6 and CBF1 recipients. This discriminant analysis showed that ACL implantation produced ectopic foci only in the recipient line (CBF1) (Table 5).
Table 5. Discriminant analysis of hematopoietic stromal progenitors originating in adherent cell layer (ACL) of long-term bone marrow cultures of B6-in-CBF1 chimeras
Time after irradiation, months | Number of chimeras tested | Recipient of implanted ACL | Foci formed/number of implants |
|---|---|---|---|
12 | 4 | B6 | 0/4 |
CBF1 | 4/4 |
Thus, MSCs in the ACLs from long-term bone marrow cultures of chimeras are only of recipient origin [14].
Linear interdependency between the foci size and amount of MSCs implanted
Various amounts of medullary tissue ranging from 1/4 to 4 femoral bone marrow plugs were transplanted and the hematopoietic cells were counted in the foci formed 1 month later. The results are shown in Table 6, where it can be seen that despite the small number of implants (3–7), the number of nucleated cells on the whole showed a linear relation with the size of the implanted bone marrow fragment. The correlation coefficient (r) was 0.97±0.014 and the extrapolation number 4.68x10-5 [5].
Table 6. The influence of ectopic marrow implant size on hematopoietic cell number in the foci formed
Experiment № | Size of implant (femoral marrow plug equivalent) | Number of implants | Hematopoietic cells/focus (x106) |
|---|---|---|---|
1 | ¼ | 5 | 2.5 |
1 | 5 | 4.7 | |
2 | ¼ | 5 | 2.6 |
½ | 7 | 3.4 | |
1 | 6 | 10.0 | |
3 | ¼ | 3 | 3.8 |
1 | 4 | 8.1 | |
4 | 1 | 5 | 16.5 |
2 | 4 | 30.3 | |
4 | 3 | 68.0 | |
5 | ¼ | 3 | 68.0 |
½ | 10 | 7.9 | |
1 | 9 | 9.8 |
In summary, stromal cells implanted under the renal capsule of syngeneic animal form a hematopoietic microenvironment only if MSCs are preserved among them, and the size of these hematopoietic foci depends solely on the number of MSC among implanted stromal cells. These results allow MSC to be studied on this model.
The size of ectopic foci is proportional to the amount of ACL implanted. ACL taken from the half of the flask bottom produces a focus that is approximately half that formed by ACL collected from the whole surface of the culture flask: 35.6x106 and 58.1x106 nucleated cells, respectively (correlation coefficient is 0.996±0.005) [12].
When transplanted under the renal capsule of a syngeneic recipient, ACL of cultures of a single femur creates a focus approximately the size of a focus formed in implantation of bone marrow freshly isolated from a single femur. This coincidence suggests that the content of stroma precursors in the culture corresponds to the explanted bone marrow dose but not to other factors, for instance, the surface of the flask bottom. In view of this, the size of foci produced by ACL from 4–6-week-old cultures of 1/2, 1 and 2 femurs was studied (Table 7).
Table 7. Correlation between bone marrow dose plated in LTBMC and the size of the ectopic foci formed
Bone marrow plated per flask (femur equivalent) | Foci formed/Number of implants | Ectopic foci size, x106 cells |
|---|---|---|
½ | 5/7 | 1.7 |
1 | 10/13 | 4 |
2 | 9/10 | 8.3 |
The size of the foci was linearly associated with the dose of the implanted bone marrow (correlation coefficient 0.999±0.001) [12].
Kinetics of stromal precursor cell proliferation in vitro and during ectopic foci formation
The time-course of the stromal precursor repopulation during the process of a creating a site of ectopic hematopoiesis was also studied. In the first 6 hrs after implantation the number of transplantable stromal precursors reduced appreciably, reaching the nadir by the end of the first day (about 20% of the number implanted). Thereafter, there was a phase of regeneration and stromal precursors recovered up to the initial level in 3 weeks. The sensitivity of the stromal precursors to the cytostatics is in good agreement with such kinetics. Normally the stromal precursors do not actually show proliferative activity, which is seen from their insensitivity to MTX. Twenty-four hours after implantation their proliferative activity remains low. During the next 24 hrs the precursors are triggered into the cell cycle synchronously. At this time up to two-thirds of the stromal precursors are killed by the cytostatics. High sensitivity to the cytostatics is observed at 3–4 and 9–10 days after implantation, but not 5–6 days after. It is not clear whether these fluctuations are incidental, or if they are related to the movement of the partially synchronized cell population through the cell cycle. Three weeks later, i.e., when the number of stromal precursors had recovered, their proliferative activity decreased to the initial low level, and remained on that level [15].
Stromal precursors also proliferate during the formation of the adherent cell layer in the LTBMC. Considering the fact that hydroxyurea affects precursors from day 2 until day 11, it seems that these cells change their proliferative status slowly, for more than 24 hours. Thus, both the implantation of BM in vivo, leading to the building of a new hematopoietic microenvironment and hematopoietic foci formation, and the explantation of BM in vitro, leading to the building of a hematopoietic microenvironment in the form of an adherent cell layer in LTBMC, are accompanied by identical changes in the proliferative status of stromal precursors. In the first 24 hours after the transfer they remain at mitotic rest, then, during the next 2 days they mobilize into the cell cycle substantially and synchronically. For the next 2 weeks they are highly active in proliferation. Afterwards, despite continuous growth of ectopic foci or ACLs, the stromal precursors do not proliferate. This is reflected in the absence of increase in the number of stromal precursors both in vivo and in vitro after 3 weeks of formation of the microenvironment.
Characteristics of stromal progenitors in vivo and in vitro
De novo formation of a stromal microenvironment after the implantation of MSC under the renal capsule
In bone marrow implantation the hematopoietic cells leave the graft, whereas the stromal precursors form a new hematopoietic stroma, which is then repopulated by host cells. The cellularity of the hematopoietic focus is proportional to the initial implant size, i.e., to the content of the stromal precursors in it. On retransplantation of the intact ectopic site, hemopoietic cells again leave the implant, as they do after the primary implantation of the bone marrow plug. Twenty-four hours after retransplantation no more than about 3% of the CFU-S remain in the focus (Table 8) [15].
Table 8. Cellularity and CFU-S content of an ectopic site of hematopoiesis as a function of time after retransplantation
Time after retransplantation, days | Number of implants | Cellularity of ectopic foci, x106 | CFU-S per ectopic foci |
|---|---|---|---|
Before | 5 | 12.1 | 3842±545 |
1 | 6 | 3.3 | 107±16 |
4 | 6 | 1.8 | 148±18 |
7 | 5 | 4.5 | 641±90 |
10 | 6 | 7.9 | 1501±329 |
The replacement of the hematopoietic cells by the recipient cells in the retransplanted focus was also confirmed karyologically [16]. Hence, it appears that when the formed site of ectopic hematopoiesis is retransplanted, the hematopoietic microenvironment is created de novo.
Self-renewal ability of MSC
The results permitted the study of the capacity of MSCs for repeated formation of ectopic foci. Nine passages failed to produce any reduction in size of the newly formed hematopoietic foci (Table 9).
Table 9. Cellularity of ectopic bone marrow foci on repeated transplantation
Transfer number | Cells in the foci, x106 |
|---|---|
1 | 12.5 |
2 | 17.2 |
3 | 20.6 |
4 | 21.3 |
5 | 22.9 |
6 | 19.8 |
7 | 35.2 |
8 | 24.7 |
9 | 11.5 |
During the serial transfer of the ectopic hematopoietic tissue without ossicles, a complete loss of the ability to form the hematopoietic focus was already apparent at the third passage. In this case no more than half of the stromal precursors remained on the ossicle (when the bone marrow is pressed out of the femur only 10–15% of the stroma precursors remain on the bone), which was verified by separate implantation of the ossicle and hematopoietic tissue from focus [15].
The self-maintenance ability of the stromal precursors was also studied in a model in which the medullary cavity was repeatedly curetted. Four successive curettages were carried out, and in each over 90% of the stromal precursors were washed out of the femur. After each curettage, the complement of stromal precursors recovered over 1–1.5 months up to 50–60% of the initial and after the fourth curettage up to 20%. Subsequent curettages proved impossible because the whole medullary cavity was filled with newly formed bone [15].
The capacity for self-maintenance of stromal precursors from cultures was studied by repeated transfer of ectopic hemopoietic foci created by them in intermediate to final recipients (Table 10).
Table 10. Self-maintenance ability of hematopoietic stromal precursors from long-term bone marrow cultures
Experiment № | Intermediate recipients | Final recipients | ||
|---|---|---|---|---|
Foci/number of implants | Cellularity, x106 | Foci/number of implants | Cellularity, x106 | |
1 | 4/4 | 12.1 | 4/4 | 1.8 |
2 | 3/4 | 2.9 | 3/3 | 0.6 |
The self-maintenance of MSCs from LTBMC proved to be low and the size of the secondary foci was 10–15% of that of foci in the intermediate recipients [11]. Thus, MSCs are maintained in LTBMC and are capable of creating a hematopoietic microenvironment on transplantation. However, self-maintenance of these precursors from LTBMC is essentially diminished.
The data obtained have demonstrated a high ability of self-maintenance of the cells transferring the hematopoietic microenvironment. Twenty-four hours after BM implantation about 10% of the stromal precursors survive. The population of the precursors in the femur is reduced to approximately the same degree after bone marrow curettage. During regeneration the stromal precursors increase to 60–100% of the initial level, hence they must undergo three or four mitoses. This is consistent with the rise in their sensitivity to S-phase specific cytostatics for the first 2 weeks after implantation. Taking into consideration that on the serial transfer of hematopoietic tissue without ossicles or on serial curettage three or four cycles of regeneration are possible, the stromal precursors are able to undergo no less than 10–12 mitoses. This value is rather underestimated since calculating the loss of precursors for differentiation was not taken into account. The high self-maintenance ability, on the one hand, and the ability to form a fully differentiated bone marrow stromal tissue on the other, suggests that the cells transferring the hematopoietic microenvironment are true mesenchymal stem cells.
Radiosensitivity of MSCs
The hematopoietic stroma function of the femoral bone marrow exposed in vitro to 500 to 2700 rad of γ-rays was also studied, using the ectopic foci formation method. Irradiation of bones with 500 rad caused no noticeable damage to the MSCs’ ability to form a hematopoietic microenvironment. Higher doses produced an exponential decrease in MSCs. The D0 estimated from linear regression (regression equation: log survival=-0.000977x+0.7200) of this portion of the curve is 444±5 rad and the extrapolation number (n) is 5.2. The results for in vitro neutron irradiation of bone marrow agreed (regression equation: log survival=-0.002697x+0.1506). A small shoulder was evident followed by an exponential survival having D0 and n of 161±19 rad and 1.4, respectively [5].
The radiosensitivity of MSCs from 5-week-old LTBMC seemed very similar to that of non-cultivated ones (regression equation: log survival=-0.089x+0.3744; D0 was 486±15 rad and n was 2.4) [17].
When high doses of irradiation were used, implantation proved unsuccessful in some cases and no ossicles with hematopoiesis were formed. One may assume that not a single MSC is preserved in such implants. The independent and random character of radiation damage of cells suggests that the existence or nonexistence of MSCs in the implant is governed by Poisson’s distribution. In this case the data on the proportion of transplant failures (P0) allow the mean MSC content in the implant (x) to be calculated using the equation x=- ln P0. The total MSC content in the femoral bone marrow can be found by taking into account the fraction that survived exposure to the given dose. These data are shown in Table 11 [5] where it is seen that the results were quite consistent on the whole.
Table 11. The effect of g irradiation on the hematopoietic microenvironment transferring MSCs in murine femoral bone marrow
Irradiation dose, rad | Implant failure/total number of implants | MSC/implant (- ln P0) | Survival fraction | MSC per femur |
|---|---|---|---|---|
2100 | 6/22 | 1.3 | 0.033 | 39.9 |
2200 | 12/20 | 0.511 | 0.025 | 20.3 |
2200 | 9/21 | 0.847 | 0.013 | 65.4 |
2500 | 7/19 | 0.999 | 0.012 | 86.3 |
2700 | 17/20 | 0.163 | 0.007 | 23.3 |
2700 | 15/19 | 0.236 | 0.003 | 78.7 |
The mean number of MSCs calculated from the proportion of transplant failures after high doses of irradiation was 52.3±11.6 per femoral bone marrow plug.
The results show that MSCs are much more radioresistant than hematopoietic stem cells, for which D0 is about 100 rad. The second feature of MSCs is their marked capability to recover from sublethal γ-ray damage, which is characterized by a extrapolation number (5.2). In the case of neutron irradiation the extrapolation number is 1.4, which is evidence that MSCs are incapable of recovery from sublethal neutron-induced damage [5].
Despite their high radioresistance MSCs were still sensitive to irradiation. After lethal irradiation and syngeneic bone marrow transplantation of CBF1 mice, the MSCs were reduced to 1/5 of the initial level and slowly regenerated to subnormal level in 6 months. The number of bone marrow cells used for reconstitution of the primary recipient did not affect MSC regeneration (Table 12) [14].
Table 12. Hematopoietic stromal precursors in lethally irradiated CBF1 mice reconstituted with different doses of syngeneic bone marrow cells
Chimera’s characteristics | Ectopic hemopoietic foci produced by femoral marrow plug implantation from reconstituted mice | |||
|---|---|---|---|---|
Cell injected | Time after reconstitution, months | Foci formed/number of implants | Foci cellularity, x106 | Ossicle weight, mg |
2x105 | 2 | 8/8 | 4.0 | 1.4 |
7.4x107 | 2 | 8/8 | 4.8 | 1.4 |
2x105 | 6 | 8/8 | 5.5 | 2.0 |
7.4x107 | 6 | 8/8 | 5.4 | 2.1 |
control | -- | 12/12 | 10.7 | 1.6 |
Two to six months after irradiation, the content of stromal progenitors in the mouse femur was, judging from the cellularity of the foci produced by them, 40–50% of the initial level in both groups of mice reconstituted both in minimal protective dose of marrow cells (2x105) and with a hundredfold dose. Thus, MSCs could be affected by high doses of irradiation and in such cases they are not able to regenerate completely.
Influence of the quality of hematopoiesis on MSCs’ proliferative potential
MSCs were compared in chimeras and double chimeras. Hematopoietic foci formed in standard recipients via BM from chimeras were approximately 2 times smaller when compared with foci formed from BM of non-irradiated mice, and 2 times bigger compared to foci formed from BM from double chimeras. These data confirm that stromal precursors are radiosensitive and unable to recover from radiation damage completely. Interestingly, secondary and tertiary chimeras’ BM formed the same small ectopic foci as double chimeras did, while the dose of irradiation affected the stroma of secondary and tertiary chimeras was 2 times lower than of double chimeras [18]. When BM from all types of chimeras tested were explanted in LTBMC, and after 3–4 weeks of cultivation were implanted under the renal capsule of syngeneic mice, foci formed from ACLs from chimeras’ BM were 75%, foci formed from ACLs from double chimeras’ BM were 20%, and ACLs from secondary and tertiary chimeras were approximately 40% by size from ACLs from non-irradiated mice. The secondary and tertiary chimeras’ stromal precursors were irradiated only once while hematopoietic cells had undergone 2 or 3 rounds of intensive proliferation during reconstitution of hematopoiesis. Thus, judging by the grade of irradiation damage, stromal cells from secondary and tertiary chimeras were similar to ordinary chimeras. Nevertheless, secondary and tertiary chimeras’ stromal precursors turned out to be affected more deeply than the same cells in ordinary chimeras. The data indicates that the stroma’s damage was determined not only by the irradiation dosage but by the quality of hematopoietic cells proliferating on it [18].
Hierarchical organization of the MSC compartment: existence of more mature than MSC-inducible precursor cells
In BM implantation, the ectopic hemopoietic focus is larger in an irradiated recipient than in a non-irradiated one in a dose-dependent manner (Table 13) [19].
Table 13. The size of the ectopic foci in irradiated recipients
Dose of irradiation | Foci size, % of control |
|---|---|
0 | 100 ± 18.8 |
1.5-2.5 | 156 ± 20 |
4.0-6.0 | 200 ± 37.5 |
7.0-8.0 | 210 ± 31.2 |
10.0-13.0 | 290 ± 68.7 |
In subsequent passages the size of the focus did not increase further (Table 14, compare with Table 9).
Table 14. Cellularity of ectopic bone marrow foci on repeated transplantation into irradiated recipients
Transfer number | Cells in the foci, x106 |
|---|---|
1 | 15.9 |
2 | 18.1 |
3 | 31.0 |
4 | 18.2 |
5 | 38.4 |
6 | 28.4 |
7 | 35.2 |
8 | 20.1 |
Hence, one may conclude that in the irradiated recipient the number of stromal precursors in an ectopic focus does not correspond to the large size of the focus. This was demonstrated more directly by implantation of similar bone marrow fragments into non-irradiated and irradiated (chimeric) recipients, subsequently testing the content of the stromal precursors in the sites formed by their retransplantation to non-irradiated recipients. In these experiments the primary focus formed in chimeras exceeded that in the non-irradiated ones by a factor of 2.2 (27.3x106 and 12.5x106). The content of the stromal precursors in both was essentially the same since the cellularities of the foci formed on transfer to the non-irradiated recipients were 10.93x106 and 11.83x106, respectively [15]. Stromal precursors from a culture also react to stimulation from the irradiated recipient, the response being much stronger than in implantation of freshly isolated bone marrow: the foci were 5–7 times larger in the irradiated recipients than in the non-irradiated ones (35.1±8x106 versus 5.3±1.2x106) (Table 15) [11].
Table 15. Size of ectopic foci produced by adherent cell layer from LTBMC in non-irradiated and irradiated recipients
Experiment № | Culture age, weeks | Non-irradiated recipients | Irradiated recipients | ||
|---|---|---|---|---|---|
| Foci formed/number of implants | Cellularity, x106 | Cellularity, x106 | Cellularity, x106 | |
1 | 2 | 2/2 | 0.7 | 2/2 | 22.5 |
2 | 4 | 0/2 | -- | 2/2 | 30.5 |
3 | 4 | 2/2 | 8.0 | 1/2 | 7.6 |
4 | 4 | 2/2 | 5.7 | 2/2 | 35.5 |
5 | 5 | 2/2 | 9.3 | 2/2 | 55.0 |
6 | 6 | 6/6 | 2.9 | 2/2 | 105.0 |
7 | 9 | 4/4 | 4.8 | 4/4 | 12.5 |
Similar results were obtained when LTBMC were established from different amounts of bone marrow (1/2, 1, 2 femurs). All cultures proved to be alike in hematopoiesis maintenance, though the MSC content in them corresponded to the dose of plated bone marrow (see Table 7). At the same time, in irradiated recipients all cultures produced foci approximately the same size (37.1, 42.7 and 38.3x106 correspondingly) [12].
The effect of hydroxyurea was estimated by the size of ectopic foci formed from treated ACLs in irradiated and non-irradiated recipients [20]. The results were similar in both types of recipients. So one may conclude that during the ACL formation both types of stromal precursors actively proliferate. MSCs functioning during the transfer into non-irradiated recipients and the more mature precursors taking part in the foci formation in the irradiated recipients.
The data suggest that the compartment of the hemopoietic stromal precursors is heterogenic and includes cells of at least two differentiation levels. Those less differentiated, MSCs able to transfer a hematopoietic microenvironment are marked by a relatively high self-maintenance, do not respond to the systemic demand of the irradiated recipient, and create a microenvironment, the size of which is proportional to the number of transferred MSCs. More mature precursors are marked by poor self-maintenance; they respond to the systemic demand of the irradiated recipient and, in the culture, to the surface of the flask bottom, and are not transplantable via in vivo transfer.
Summarizing the data presented above, the compartment of stromal bone marrow cells has a hierarchical structure. There are true mesenchymal stem cells (MSCs) capable of both self-maintaining and differentiating into all stromal lineages, and more mature inducible stromal precursors, which keep the ability for multipotential differentiations while losing their self-renewing ability. MSCs are mainly in mitotic rest and are not sensitive to the systemic demand, while more mature precursors proliferate more easily in the case of systemic requirements.
More mature inducible stromal precursors are sensitive to the unknown factor(s) released after irradiation. When injected during foci formation sera from irradiated mice also stimulate these precursors, resulting in increased size of the foci formed – the size of the foci was 19.5±1. 8x106 compared with 14±1.5x106 in control mice [19]. Addition of sera from irradiated mice to the LTBMC also increases the number of stromal cells in the ACLs (Table 16) [21].
Table 16. Influence of the sera from irradiated mice on the number of cells in the ACLs from LTMBC
Group | Cell number per well, х 103 |
|---|---|
control (no additional serum) | 118 ± 4 |
2% of sera from non-irradiated mice | 131 ± 7 |
0.5% of sera from irradiated mice | 160 ± 4 |
1 % of sera from irradiated mice | 185 ± 5 |
2 % of sera from irradiated mice | 206 ± 5 |
In order to define the organ producing the unknown factor(s), various organs of irradiated mice were co-transplanted simultaneously with the implantation of the BM plug under the renal capsule. Intravenous injection of irradiated sera as well as implantation of 5–6 irradiated bones under the skin enhanced the growth of stromal cells in the foci formed (Table 17) [21].
Table 17. Analysis of the various organs of irradiated mice for their stroma-stimulating activity
Recipients | The organ from irradiated mice, transplantation site | Foci size, х 106 |
|---|---|---|
intact (non-irradiated) | 9.0 ± 1.7 | |
irradiated | 21.1 ± 6.2 | |
intact | BM from 6 femurs, under the skin | 8.6 ± 2.3 |
intact | 5–6 femurs, under the skin | 22.0 ± 4.1 |
intact | Thymus, under the renal capsule | 14.8 ± 3.4 |
intact | Equivalent of ½ of the spleen, intravenously | 10.5 ± 1.2 |
intact | 1/3 of the spleen, under the renal capsule | 11.8 ± 3.3 |
intact | the spleen, under the skin | 13.1 ± 2.8 |
intact | 1/3 of the liver, under the skin | 14.8 ± 3.2 |
intact | Sera from irradiated mice, intravenously | 20.1 ± 1.5 |
intact | Sera from non-irradiated mice, intravenously | 14.0 ± 2.8 |
Thus, the unknown factor(s) stimulating the growth of stromal inducible precursor cells are produced in the irradiated bones and secreted into the blood serum.
The regulation of MSCs in vivo by hematopoietic growth factors
Regulation of MSCs by soluble factors remains obscure. During the formation of the hematopoietic microenvironment MSCs are affected by G-CSF. When recipients of BM were injected over 10 or 17 days beginning from the day after implantation of BM under the renal capsule it dramatically decreased size of the foci formed (Table 18).
Table 18. Influence of G-CSF on the ectopic foci formation from the bone marrow of intact mice
G-CSF treatment | Bone marrow implantation | Foci retransplantation | ||||
|---|---|---|---|---|---|---|
Implant number | Cellularity, x106 | Ossicle weight, mg | Implant number | Cellularity, x106 | Ossicle weight, mg | |
Control | 4 | 8.3±1.7 | 2.2±0.4 | 4 | 16.2±3.3 | 2.3±0.5 |
10 days | 4 | 5.3±0.7 | 2.7±0.7 | 4 | 9.0±1.8 | 1.9±0.5 |
17 days | 6 | 3.4±0.6 | 2.0±0.4 | 6 | 1.7±0.3 | 1.3±0.4 |
Obviously, when administered during the active proliferation and differentiation of MSC, G-SCF inhibits their proliferation (judging from the decreased size of the foci formed); moreover, it diminishes the number of MSCs themselves as was shown by retransplantation of the foci [22].
Conversely, cytokine treatment of the MSCs in their steady-state (in the intact bone marrow increases the number of these stromal precursors (Table 19).
Table 19. Size of the ectopic foci formed from the bone marrow of mice treated with cytocines
Group | Bone marrow implantation | Foci retransplantation | ||||
|---|---|---|---|---|---|---|
Implant number | Cellularity, x106 | Ossicle weight, mg | Implant number | Cellularity, x106 | Ossicle weight, mg | |
Control | 9 | 6.5±1.0 | 2.0±0.2 | 4 | 5.9±1.2 | 2.6±0.4 |
G-CSF, 6 days | 4 | 7.4±2.2 | 1.1±0.2 | |||
G-CSF, 10 days | 3 | 10.7±2.0 | 1.0±0.2 | 3 | 11.3±2.9 | 3.0±0.6 |
G-CSF, 17 days | 4 | 9.2±1.0 | 3.3±0.7 | 3 | 13.3±2.8 | 3.5±0.7 |
G-CSF+SCF, 6 days | 4 | 6.4±1.6 | 2.2±0.5 | |||
G-CSF+SCF, 10 days | 4 | 12.8±1.5 | 2.4±0.6 | |||
G-CSF+SCF, 17 days | 4 | 18.4±3.9 | 1.7±0.5 | 5 | 19.5±4.2 | 3.2±0.6 |
The combination of G-CSF with SCF and the longest treatment (for 17 days) had a maximal effect on the MSC number in the bone marrow of treated mice. In the case of G-CSF treatment this effect was transient and did not last for a month, in the case of cytokine combination, however, the increase in the number of MSCs was stable for at least a month. Cytokine treatment did not affect the osteogenic potential of MSCs either during stroma formation or in the intact bone marrow [22].
Thus, during the building of ectopic hematopoietic foci when stromal precursors are proliferating and differentiating, pharmacological concentrations of G-CSF inhibit the process of foci formation and diminish the number of stromal precursors in them. When affecting the mature non-proliferating bone marrow stroma, cytokines increase the number of MSCs.
Conclusions
Summarizing the works of J. L. Chertkov, it is possible to describe the main features of MSCs. These cells are capable of transferring a hematopoietic microenvironment due to both their high proliferative potential and their ability to differentiate into all bone marrow stromal lineages, including bone, cartilage, and marrow stromal cells. MSCs are more radioresistant than HSCs but they still suffer from radiation and their damage could not be fully recovered. Impaired hematopoiesis also influences the MSCs. The compartment of MSCs and stromal precursor cells is organized hierarchically. Therefore, J. L. Chertkov described the main features of MSCs from many sides using the functional assay.
Acknowledgements
Irina Shipounova and Nina Drize for preparing the compilation of Chertkov’s works on hematopoietic stromal microenvironment.
Gurevich O. A., Udalov G. A., Samoylina N. L., Samoylova R. S., Lemeneva N. L., Todria T. V., Olovnikova N. I., Olshanskaya Y. V., Shiponova (Nifontova) I. N., Ershler M. A. and Drize N. I. as co-authors of his works.
References
3. Olovnikova NI, Drize NJ, Ershler MA, Nifontova IN, Belkina EV, Nikolaeva TN, Proskurina NV, Chertkov JL. Developmental fate of hematopoietic stem cells: the study of individual hematopoietic clones at the level of antigen-responsive B lymphocytes. Hematol J. 2003;4(2):146-150.
4. Drize NJ, Olshanskaya YV, Gerasimova LP, Manakova TE, Samoylina NL, Todria TV, Chertkov JL. Lifelong hematopoiesis in both reconstituted and sublethally irradiated mice is provided by multiple sequentially recruited stem cells. Exp Hematol. 2001;29(6):786-794.
5. Chertkov JL, Gurevitch OA. Radiosensitivity of progenitor cells of the hematopoietic microenvironment. Radiat Res. 1979;79(1):177-186.
6. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9(5):641-650.
7. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005;7(5):393-395.
8. Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977;91(3):335-344.
9. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6(2):230-247.
10. Udalov GA, Gurevich OA, Chertkov IL. Origin of hematopoietic cells in a syngenous and semisyngenous focus of heterotopic hematopoiesis. Biull Eksp Biol Med. 1977;83(5):584-586.
11. Chertkov JL, Drize NJ, Gurevitch OA, Udalov GA. Hemopoietic stromal precursors in long-term culture of bone marrow: I. Precursor characteristics, kinetics in culture, and dependence on quality of donor hemopoietic cells in chimeras. Exp Hematol. 1983;11(3):231-242.
12. Chertkov JL, Drize NJ, Gurevich OA. Hemopoietic microenvironment and hemopoietic stroma precursors. Recent advances in haematology immunology and blood transfusion : proceedings of the plenary sessions of the joint meeting of the 19th Congress of the International Society of Haematology and the 17th Congress of the International Society of Blood Transfusion, Budapest, August 1-7, 1982, Eds. Susan R. Hollán; International Society of Haematology, 12,1983;133-147.
13. Gurevich OA, Drize NI, Chertkov IL. Importance of cell contacts for the differentiation of the precursor cells of hematopoietic stroma in long-term bone marrow cultures. Biull Eksp Biol Med. 1982;94(8):97-100.
14. Chertkov JL, Drize NJ, Gurevitch OA, Samoylova RS. Origin of hemopoietic stromal progenitor cells in chimeras. Exp Hematol. 1985;13(11):1217-1222.
15. Chertkov JL, Gurevitch OA. Self-maintenance ability and kinetics of haemopoietic stroma precursors. Cell Tissue Kinet. 1980;13(5):535-541.
16. Chertkov JL, Gurevich OA, Udalov GA. Role of bone marrow stroma in the phenomenon of hybrid resistance. Biull Eksp Biol Med 1979 Apr; 87(4):337-40.
17. Gurevich OA, Chertkov JL. Radiosensitivity of hemopoietic stroma precursors from long-term bone marrow culture. Radiobiology. 1983;23(4):521-523.
18. Gurevich OA, Drize NI, Udalov GA, Chertkov IL. Effect of hematopoiesis on progenitor bone marrow stromal cells. Biull Eksp Biol Med. 1982;94(10):115-117.
19. Chertkov JL, Gurevitch OA. Hematopoietic stem cell and its microenvironment. Moscow, Meditzina 1984. Russian.
20. Gurevich OA, Drize NJ, Chertkov JL. Proliferation of cells-precursors of hematopoietic microenvironment in murine long-term bone marrow culture. Bull Exp Biol Med. 1984;XCVIII(11):612-614.
21. Drize NI, Ershler MA, Chertkov IL. Radiation-induced hemopoietic cell growth factor: detection in a culture. Bull Exp Biol Med. 2001;132(6):1213-1215.
22. Drize NJ, Chertkov JL. Influence of cytokine (G-CSF and SCF) treatment on the murine precursors of hematopoietic stroma. Bull Exp Biol Med. 1998;125(2):204-206.
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Иосиф Л. Чертков, Ольга А. Гуревич, Геннадий А. Удалов, Ирина Н. Шипунова, Нина И. Дризе
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18017" ["VALUE"]=> array(2) { ["TEXT"]=> string(2489) "<p>Данная работа суммирует достижения профессора Иосифа Львовича Черткова в изучении клеток-предшественниц кроветворного стромального микроокружения. В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2477) "Данная работа суммирует достижения профессора Иосифа Львовича Черткова в изучении клеток-предшественниц кроветворного стромального микроокружения. В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.
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" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18032" ["VALUE"]=> array(2) { ["TEXT"]=> string(702) "<p>The manuscript summarizes the works of Prof. Joseph Chertkov that are dedicated to precursor cells in the hematopoietic stromal microenvironment. Unique functional analysis was used in these investigations. The properties of stem cells in the hematopoietic microenvironment such as self-renewal capacity and the ability to differentiate into all stromal lineages are described. The hierarchical structure of stromal precursor cells compartment is proposed. Some elements of the regulatory pathways of stromal precursor cells are described. This compilation reflects the importance of Prof. Chertkov’s contribution to the investigation of stromal precursor cells and hematopoiesis. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(690) "The manuscript summarizes the works of Prof. Joseph Chertkov that are dedicated to precursor cells in the hematopoietic stromal microenvironment. Unique functional analysis was used in these investigations. The properties of stem cells in the hematopoietic microenvironment such as self-renewal capacity and the ability to differentiate into all stromal lineages are described. The hierarchical structure of stromal precursor cells compartment is proposed. Some elements of the regulatory pathways of stromal precursor cells are described. This compilation reflects the importance of Prof. Chertkov’s contribution to the investigation of stromal precursor cells and hematopoiesis.
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В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2477) "Данная работа суммирует достижения профессора Иосифа Львовича Черткова в изучении клеток-предшественниц кроветворного стромального микроокружения. В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(2477) "Данная работа суммирует достижения профессора Иосифа Львовича Черткова в изучении клеток-предшественниц кроветворного стромального микроокружения. В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.
" } } } [1]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "67" ["~IBLOCK_SECTION_ID"]=> string(2) "67" ["ID"]=> string(4) "1347" ["~ID"]=> string(4) "1347" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(85) "Управление библиографическими списками и Web 2.0" ["~NAME"]=> string(85) "Управление библиографическими списками и Web 2.0" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(19) "15.08.2017 14:37:31" ["~TIMESTAMP_X"]=> string(19) "15.08.2017 14:37:31" ["DETAIL_PAGE_URL"]=> string(84) "/ru/archive/tom-2-nomer-2-6/forum/upravlenie-bibliograficheskimi-spiskami-i-web-2-0/" ["~DETAIL_PAGE_URL"]=> string(84) "/ru/archive/tom-2-nomer-2-6/forum/upravlenie-bibliograficheskimi-spiskami-i-web-2-0/" ["LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["~LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["DETAIL_TEXT"]=> string(10941) "Introduction
Reference management software allows researchers to create a personal electronic collection of relevant scholarly publications, and to use this collection to write their own scholarly works. Some of the earliest programs (e.g. Endnote and BibTeX) have now been around for 25 years, and their core functions remain unchanged. The first big change came around 15 years ago when references were no longer typed in by hand, but rather retrieved from the Internet. Another important change started five years ago in the context of what is typically called Web 2.0. Reference managers no longer were used as software on a single desktop computer. They now more often than not are web-based applications (with or without synchronization to a desktop version), and this allows easy sharing of references between several users, computers and/or other web applications. This trend has led to a number of new reference managers, both commercial and freely available.
Reference managers help researchers by performing three basic functions:
1) Searching: find relevant scientific literature,
2) Storing: store the results of that search in a personal database for later retrieval, and
3) Writing: insert references when writing a manuscript.
Although all three functions could also be performed without specialized software, a manual approach is not recommended for managing anything beyond a handful of references. Managing references manually is much slower and prone to errors, e.g., when renumbering all references in a manuscript after inserting a new citation.
In the next sections, we will look at the three basic reference manager functions in more detail, with special emphasis on how the newer Web-based reference managers enhance some of these functions with “social” features.
Searching
All reference managers can import references from bibliographic databases, either by directly searching these databases (PubMed, Scopus, Web of Science, Google Scholar, etc.), and/or via so-called bookmarklets. Bookmarklets are specialized bookmarks for web browsers that retrieve references from web pages, e.g., the result of a PubMed search. Both strategies have their advantages, but for most users there is no real difference. Interesting references are also showing up in other places besides bibliographic databases. Most commonly this is a journal table of contents received via email or RSS reader, but it can also be a blog post or even a Twitter message. In order to retrieve this reference information, users usually first have to follow a link to a bibliographic database or journal web page.
A traditional search strategy typically uses keywords, author and journal names, and publication dates. Because web-based reference managers such as CiteULike or Mendeley store millions of references by thousands of users, they also offer a very powerful “social” search. They can show you the references of users with similar interests, or papers similar to the paper you just imported. This “social” search requires a critical mass of users, but might in a few years surpass traditional search strategies in popularity. Sharing references in private or public groups is already a very popular feature of web-based reference managers. Reading lists — lists of references required for a particular course — are one typical use.
Storing
Reference managers are databases that store references. In the life sciences a reference is typically a journal article, and sometimes a conference abstract, book chapter, or web page. But reference managers can also handle a long list of other references. Among the 48 reference types supported in the latest version of Endnote (Endnote X4), some of the lesser known are online database, audiovisual material, grant, blog, and research dataset. This wider definition of a reference looks not unlike the bookmarks we store with our web browser. Bookmarks can be stored in specialized websites (e.g., delicious), and several of these so-called social bookmarking sites also handle scientific references (CiteULike being the most popular).
Since almost all scholarly publications are now published in electronic form, reference managers (most notably Papers) a few years ago started to not only manage references, but also store the fulltext PDF files associated with them. This is the most convenient way to store these PDF files. And it has another advantage: we can do powerful fulltext searches of the publications stored in our reference manager. Many reference managers can import PDF files and extract the reference information from the PDF file. And some of them have an integrated PDF viewer that allows highlighting of text and note taking.
As reference managers are basically databases, they should allow the user to import and export references (RIS is the best standard file format), find duplicate records, or group references by subject or keyword. Only some reference managers can also group references by author or journal, or list all references cited by a particular reference.
Many reference managers offer a web-based version. This allows users to have the same reference database on more than one computer and to share references with others. Whereas some reference managers (e.g. CiteULike, RefWorks) are only web-based, others (e.g., Mendeley, Endnote, Zotero) synchronize a desktop with a web version. This year we have seen a proliferation of reference management tools for mobile devices such as the iPhone, and also the first reference managers for the iPad.
Writing
Reference managers are a big time saver in manuscript writing. They help in inserting citations into the text and automatically create a bibliography in the desired citation style. Although many reference managers now come with more than 1000 different citation styles, only a few of them (e.g., Endnote or Refworks) allow the user to edit them — an important feature for some users. Not all reference managers have a word processor plugin, and if they do they often only support Microsoft Word and maybe OpenOffice. The built-in reference management features of the latest version of Microsoft Word (Word 2007 or Word 2008 for Macintosh) are very rudimentary and not recommended.
Almost all scientific papers are now written by more than one author. Collaborative online writing tools such as Google Docs or Zoho Writer facilitate the writing process, as authors don’t have to repeatedly send around draft versions of manuscripts via email. Unfortunately no reference manager directly supports these online tools beyond a simple copy and paste.
Links
Connotea
Endnote/Endnote Web
Refworks
Zotero
Mendeley
CiteULike
Jabref
Papers
Citavi
Table 1. Some popular reference managers with Web 2.0 features
(Animation by Viktoriya Levenko)
Conclusions
Reference management software is currently undergoing a lot of exciting changes, and now is a good time to test some of the programs mentioned in this article. Several of the newer reference managers are free to use, so cost shouldn’t be a reason not to start using such a tool. CiteULike and other web-based tools can be used right away without installing any software; downloading and installing one of the free tools (e.g. Zotero or Mendeley) also takes less than an hour. Every reference manager has strengths and weaknesses; the comparison chart can help with finding the right tool to get started. It is also a good idea to start with a reference manager that your colleagues use. Not only can they help you with questions, but you also want to use the same reference manager when writing a manuscript together.
Acknowledgements
I declare no conflict of interest.
References
1. Hull D. et al. Defrosting the digital library: bibliographic tools for the next generation web. PLoS Comput Biol. 2008;4(10):pp.e1000204
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000204
2. Innovations in Reference Management Workshop
3. Reference Manager Overview
Introduction
Reference management software allows researchers to create a personal electronic collection of relevant scholarly publications, and to use this collection to write their own scholarly works. Some of the earliest programs (e.g. Endnote and BibTeX) have now been around for 25 years, and their core functions remain unchanged. The first big change came around 15 years ago when references were no longer typed in by hand, but rather retrieved from the Internet. Another important change started five years ago in the context of what is typically called Web 2.0. Reference managers no longer were used as software on a single desktop computer. They now more often than not are web-based applications (with or without synchronization to a desktop version), and this allows easy sharing of references between several users, computers and/or other web applications. This trend has led to a number of new reference managers, both commercial and freely available.
Reference managers help researchers by performing three basic functions:
1) Searching: find relevant scientific literature,
2) Storing: store the results of that search in a personal database for later retrieval, and
3) Writing: insert references when writing a manuscript.
Although all three functions could also be performed without specialized software, a manual approach is not recommended for managing anything beyond a handful of references. Managing references manually is much slower and prone to errors, e.g., when renumbering all references in a manuscript after inserting a new citation.
In the next sections, we will look at the three basic reference manager functions in more detail, with special emphasis on how the newer Web-based reference managers enhance some of these functions with “social” features.
Searching
All reference managers can import references from bibliographic databases, either by directly searching these databases (PubMed, Scopus, Web of Science, Google Scholar, etc.), and/or via so-called bookmarklets. Bookmarklets are specialized bookmarks for web browsers that retrieve references from web pages, e.g., the result of a PubMed search. Both strategies have their advantages, but for most users there is no real difference. Interesting references are also showing up in other places besides bibliographic databases. Most commonly this is a journal table of contents received via email or RSS reader, but it can also be a blog post or even a Twitter message. In order to retrieve this reference information, users usually first have to follow a link to a bibliographic database or journal web page.
A traditional search strategy typically uses keywords, author and journal names, and publication dates. Because web-based reference managers such as CiteULike or Mendeley store millions of references by thousands of users, they also offer a very powerful “social” search. They can show you the references of users with similar interests, or papers similar to the paper you just imported. This “social” search requires a critical mass of users, but might in a few years surpass traditional search strategies in popularity. Sharing references in private or public groups is already a very popular feature of web-based reference managers. Reading lists — lists of references required for a particular course — are one typical use.
Storing
Reference managers are databases that store references. In the life sciences a reference is typically a journal article, and sometimes a conference abstract, book chapter, or web page. But reference managers can also handle a long list of other references. Among the 48 reference types supported in the latest version of Endnote (Endnote X4), some of the lesser known are online database, audiovisual material, grant, blog, and research dataset. This wider definition of a reference looks not unlike the bookmarks we store with our web browser. Bookmarks can be stored in specialized websites (e.g., delicious), and several of these so-called social bookmarking sites also handle scientific references (CiteULike being the most popular).
Since almost all scholarly publications are now published in electronic form, reference managers (most notably Papers) a few years ago started to not only manage references, but also store the fulltext PDF files associated with them. This is the most convenient way to store these PDF files. And it has another advantage: we can do powerful fulltext searches of the publications stored in our reference manager. Many reference managers can import PDF files and extract the reference information from the PDF file. And some of them have an integrated PDF viewer that allows highlighting of text and note taking.
As reference managers are basically databases, they should allow the user to import and export references (RIS is the best standard file format), find duplicate records, or group references by subject or keyword. Only some reference managers can also group references by author or journal, or list all references cited by a particular reference.
Many reference managers offer a web-based version. This allows users to have the same reference database on more than one computer and to share references with others. Whereas some reference managers (e.g. CiteULike, RefWorks) are only web-based, others (e.g., Mendeley, Endnote, Zotero) synchronize a desktop with a web version. This year we have seen a proliferation of reference management tools for mobile devices such as the iPhone, and also the first reference managers for the iPad.
Writing
Reference managers are a big time saver in manuscript writing. They help in inserting citations into the text and automatically create a bibliography in the desired citation style. Although many reference managers now come with more than 1000 different citation styles, only a few of them (e.g., Endnote or Refworks) allow the user to edit them — an important feature for some users. Not all reference managers have a word processor plugin, and if they do they often only support Microsoft Word and maybe OpenOffice. The built-in reference management features of the latest version of Microsoft Word (Word 2007 or Word 2008 for Macintosh) are very rudimentary and not recommended.
Almost all scientific papers are now written by more than one author. Collaborative online writing tools such as Google Docs or Zoho Writer facilitate the writing process, as authors don’t have to repeatedly send around draft versions of manuscripts via email. Unfortunately no reference manager directly supports these online tools beyond a simple copy and paste.
Links
Connotea
Endnote/Endnote Web
Refworks
Zotero
Mendeley
CiteULike
Jabref
Papers
Citavi
Table 1. Some popular reference managers with Web 2.0 features
(Animation by Viktoriya Levenko)
Conclusions
Reference management software is currently undergoing a lot of exciting changes, and now is a good time to test some of the programs mentioned in this article. Several of the newer reference managers are free to use, so cost shouldn’t be a reason not to start using such a tool. CiteULike and other web-based tools can be used right away without installing any software; downloading and installing one of the free tools (e.g. Zotero or Mendeley) also takes less than an hour. Every reference manager has strengths and weaknesses; the comparison chart can help with finding the right tool to get started. It is also a good idea to start with a reference manager that your colleagues use. Not only can they help you with questions, but you also want to use the same reference manager when writing a manuscript together.
Acknowledgements
I declare no conflict of interest.
References
1. Hull D. et al. Defrosting the digital library: bibliographic tools for the next generation web. PLoS Comput Biol. 2008;4(10):pp.e1000204
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000204
2. Innovations in Reference Management Workshop
3. Reference Manager Overview
Мартин Феннер
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Keywords
reference management, Web 2.0, citation
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Martin Fenner, MD
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Keywords
reference management, Web 2.0, citation
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Reference management software has been used by researchers for more than 20 years to find, store, and organize references, and to write scholarly papers. Recently developed collaborative web-based tools have resulted in a number of interesting new features, and in a number of new reference managers. These developments are changing which reference managers we use, and how we use them.
Keywords
reference management, Web 2.0, citation
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Carl-Neuberg-Str. 1, Hannover Medical School, 30625 Hannover, Germany
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Не так давно появились коллективные сетевые ресурсы, которые открыли новые интересные возможности и способствовали созданию новых приложений по работе с библиографиями. Эти наработки специфичны для каждого отдельного приложения. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(809) "Программное обеспечение по управлению библиографическими списками используется уже более 20 лет для поиска, хранения и систематизации библиографического материала, а также для написания научных статей. Не так давно появились коллективные сетевые ресурсы, которые открыли новые интересные возможности и способствовали созданию новых приложений по работе с библиографиями. Эти наработки специфичны для каждого отдельного приложения.
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(809) "Программное обеспечение по управлению библиографическими списками используется уже более 20 лет для поиска, хранения и систематизации библиографического материала, а также для написания научных статей. Не так давно появились коллективные сетевые ресурсы, которые открыли новые интересные возможности и способствовали созданию новых приложений по работе с библиографиями. Эти наработки специфичны для каждого отдельного приложения.
" } } } [2]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "75" ["~IBLOCK_SECTION_ID"]=> string(2) "75" ["ID"]=> string(4) "1363" ["~ID"]=> string(4) "1363" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(195) "Трансплантация гемопоэтических стволовых клеток при тяжёлых аутоиммунных болезнях: успехи и перспективы" ["~NAME"]=> string(195) "Трансплантация гемопоэтических стволовых клеток при тяжёлых аутоиммунных болезнях: успехи и перспективы" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(19) "21.09.2017 14:43:23" ["~TIMESTAMP_X"]=> string(19) "21.09.2017 14:43:23" ["DETAIL_PAGE_URL"]=> string(145) "/ru/archive/tom-2-nomer-2-6/obzornye-stati-/transplantatsiya-gemopoeticheskikh-stvolovykh-kletok-pri-tyazhyelykh-autoimmunnykh-boleznyakh-uspekh/" ["~DETAIL_PAGE_URL"]=> string(145) "/ru/archive/tom-2-nomer-2-6/obzornye-stati-/transplantatsiya-gemopoeticheskikh-stvolovykh-kletok-pri-tyazhyelykh-autoimmunnykh-boleznyakh-uspekh/" ["LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["~LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["DETAIL_TEXT"]=> string(52279) "Introduction
Stem cell therapy for severe autoimmune diseases (AD), generally as hematopoietic stem cell transplantation (HSCT), both allogeneic and autologous, but also more recently as gene therapy-assisted autologous HSCT, has become one of the hottest areas of clinical immunology. It has been developing progressively in the last decades, and has generated “excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature” [6]. The utilization of stem cells to promote regenerative medicine must be distinguished from the purpose of suppressing autoimmune cellular and humoral aggression. This does not mean that both areas aren’t tightly connected, since supplying new pancreatic beta cells to patients with type I diabetes, whether by islet cell transplantation or by boosting their numbers by reprogramming pancreatic acinar cells, cannot resolve the disease if the autoimmune process is not eliminated [61]. In some clinical entities both effects coincide. An appropriate example is aplastic anemia (AA) and some of its minor variants (pure red cell aplasia-PRCA, pure white cell aplasia-PWCA), in which allogeneic HSCT both suppresses autoimmunity and provides new HSC [62]. In all the other autoimmune conditions this double effect has not been demonstrated conclusively.
The utilization of HSCT, overwhelmingly of the autologous modality, has been growing impressively in the last few years, and is still increasing steadily [28, 47]. Autologous HSCT (ASCT) relies on an extensive debulking of the autoaggressive immune system, followed by the re-infusion of the patients’ HSC (commonly identified as CD34+ cells). The allogeneic procedure is based on the substitution of the faulty immune system by a new healthy one, theoretically capable of eradicating the autoimmune clones by means of the classical combination of high-dose immunosuppressive therapy and a Graft-versus-Autoimmunity (GVA) effect, which will be discussed later. Whether this last intervention will be capable of achieving the Holy Grail of self-tolerance [15] is still not established, given the complexity of the pathogenesis of ADs, including the persisting antigenicity of altered “self” proteins [12] and some paradoxical post-transplant relapses despite full donor chimerism, which will be discussed later.
A brief historical recapitulation
Two streams of research, experimental and clinical, are at the origin of the increasing utilization of HSCT, autologous and allogeneic, for SADs [34]. The first animal studies had shown that the transfer of spleen and/or whole marrow cells to immunosuppressed mice could reproduce murine lupus. The culprit cells were shown to be stem or lymphoid progenitors. The next step was to ascertain whether, contrarily, healthy HSC were capable of curing experimental ADs. Human blood SC were capable of suppressing antibody production in lupus mice, perhaps the first demonstration of a curative effect by xenogeneic HSCT. More recently, it has elegantly been shown that the nonmyeloablative transplantation of purified allogeneic HSC not only prevented, but also induced stabilization or reversal of lupus symptoms in NZB mice [50]. Durable mixed chimerism was also efficacious, a point that will be discussed later. A further experimental improvement has been the intra-bone injection of HSC [21].
The resolution of experimental ADs by means of healthy, compatible allo-SCT was to be expected, considering the overwhelming genetic predisposition of inbred strains of mice, which differs from the intricacies of human ADs, in which there is a complex relationship between genetic, environmental and regulatory factors, and where impaired mechanisms of thymic selection interact, in still poorly elucidated ways, with genetic factors. As already mentioned, a GVA effect has been postulated [33], and theoretically dissected in 6 different mechanisms [53], with immune-mediated abrogation of autoreactive clones in the foreground. In practice, donor-derived immune cells are capable of mediating an anti-autoimmune effect either specifically, or as a part of a more general alloimmune reaction. In experimental autoimmune encephalomyelitis (EAE) it was shown that active alloreactivity was associated with the greatest GVA effect [60]. The second stream in favor of allo-SCT came from the clinical observation of patients affected by coincidental diseases, that is patients with ADs having developed a hematologic malignancy for which they received an allo-SCT, and were ultimately cured of both diseases [35]. There were even cases in which allo-BMT transferred the AD of the donor to the recipient, but cured the latter of his former AD.
The rationale for an apparently paradoxical procedure such as autologous HSCT, in which the patients’ immune cells, despite varying degrees of HSC depletion in vitro and/or in vivo, are administered back to them, came from the pioneering studies by van Bekkum and his group, who were able to cure EAE and adjuvant arthritis (AA), both models of human multiple sclerosis (MS) and rheumatoid arthritis (RA), by means of autologous (“pseudoautologous”) HSCT [58]. These results considerably strengthened the philosophy of autologous HSCT for human ADs, even if it was pointed out later that in animal models the abnormality of the antigen-induced type seems to reside in immunocompetent T/B cells but not in the HSC, and therefore ASCT may be curative, while in spontaneous ADs new, unaffected HSC were necessary to achieve a cure [22]. In any case, the utilization of ASCT is now widely accepted for treating severe, refractory ADs.
A powerful immunosuppressive therapy for SADs has been developed at Johns Hopkins University in Baltimore, where such patients are treated with high-dose cyclophosphamide (CY) alone, with an inevitable delay of marrow and blood reconstitution, but with results that do not differ significantly from those obtained by ASCT [5].
Finally, two new approaches appear to be integrating this area. Mesenchymal stem cells (MSC) possess several immunomodulatory properties [44], have been shown to significantly ameliorate Graft-versus-Host Disease [25] (GVHD), and have been considered a valuable therapeutic option for SADs [56]. However the role of this kind of cellular therapy in human AD, whether associated with ASCT or not, is still to be established. Another fascinating approach is based on the idea of achieving antigen-specific tolerance to treat refractory ADs, even if translating such therapies from bench to bedside is still mainly theoretical. An approach combining HSCT and transduction of the culprit self-antigens in autologous HSCs in order to achieve central (thymic) tolerance has been developed by Alderuccio and his group [2], although only in animal experiments with organ-specific autoimmune conditions at this stage.
Autologous transplantation: progress and questions
In contrast to the long interval having taken place between the first allogeneic transplants for animal ADs and translational clinical trials, ASCT quickly followed the experimental investigations. It was proposed by myself for severe SLE in 1993 [36], and then for ADs in general in 1995 [30]. The first transplants were performed for a connective tissue disease [54] and for severe SLE [32]. The following utilization of ASCT for SADs grew almost exponentially, so much so that, besides the continually increasing registered transplants in the EBMT and CIBMTR registries, a recent study by Dominique Farge et al has analyzed 900 patients [14]. Excellent reviews of specific diseases have been published recently, and a monographic issue of Autoimmunity has just been devoted to this theme [28]. Here, I shall focus on the most significant and contemporary questions.
1. Autologous HSCT for ADs has been considered a relatively safe procedure from its inception, but is it becoming safer?
Autoimmune diseases represent an extremely heterogenous spectrum of diseases, and in most of them severe-refractory forms have a poor prognosis and a greatly impaired quality of life. One cannot disagree, however, with Burt’s statement that “Treatment-related mortality needs to be very low for non-malignant diseases”1. Treatment-Related Mortality (TRM) reached 12% in the initial EBMT Registry, decreased to 7 +3% in 2005, and finally did not exceed 5% in the most recent EBMT study [14]. In this last study evidence was also found of a clear center effect, indicating that experienced teams that are well acquainted with the multi-organ involvement of SADs produce superior results. In the case of a single disease such as SLE, a collection of 162 patients transplanted in 30 Centers showed a TRM of 11% [29], However of 200 patients transplanted at Northwestern University, Chicago, the TRM using non-myeloablative conditioning regimens in 200 patients was 1.5% [8]. This does not mean, of course, that TRM cannot grow much higher in very severe conditions such as advanced scleroderma. Scleroderma-related organ disfunction contributed to treatment-related deaths [43]. In conclusion, the answer to this first question is that ASCT may be considered reasonably safe when performed by experienced teams, appropriate conditioning regimens, and on patients who are not too disease-compromised. These data need to be counterbalanced by mortality from disease progression, and require the adoption of inclusion and exclusion criteria for each category of diseases, which cannot be detailed here. Although the inclusion of patients within approved or investigational protocols is the best policy, it must be realized that, in selected patients with advanced, refractory SADs, the decision to perform ASCT will ultimately rely on a combination of clinical acumen, experienced teams, and a good patient-doctor relationship.
2. Which are the most appropriate mobilization and conditioning regimens?
The source of HSCs was initially the bone marrow (BM), but has now changed to the peripheral blood (PB) following mobilization procedures. In the previously mentioned EBMT study of 900 patients the source was PB in 827 cases [43]. The most popular mobilizing regimens generally consist of combinations of cyclophosphamide (CY) and G-CSF [47]. Mobilizing regimens incorporating CY (from 2 to 4g/m2) have the additional, significant advantage of acting as an important therapeutic procedure per se (therapeutic mobilization). In our own experience of 9 SLE patients the achievement of a complete remission (CR) following mobilization with CY 4g/m2 enabled us, in 2 cases, to dispense from performing the initially programmed ASCT.
A variety of conditioning regimens have been utilized, but it could be shown that high-intensity protocols were followed by a lower probability of disease progression, albeit with a higher risk of TRM [16]. The strategy of performing intense immunosuppression without affecting the whole of the hematopoietic system is most generally accepted, taking into account that biologics such as Rituximab have a longer immunosuppressive activity than any chemotherapeutic agent. A combination of both strategies, in which Rituximab 500 mg is given before and after the regular 200 mg/kg CY protocol (the “sandwich technique”), is being currently utilized at Northwestern University, Chicago (USA). Anti-CD20 immunotherapy for the control of relapse following ASCT in patients with rheumatoid arthritis (RA) had been already utilized with success [41], and the strategy of using an additional immunotherapy in this area is attractive. Unfortunately a devastating complication, progressive multifocal leukoencephalopathy (PML), due to the activation of the John Cunningham virus (JCV), has been reported in a disquieting proportion of patients having been immunosuppressed with biological agents (Natalizumab, Rituximab). A recent review reported 52 patients as having developed PML, 7 of which had received HSCT (3 allogeneic, 4 autologous) for lymphoproliferative diseases [9]. Awareness is obviously needed of the potential for PML among Rituximab-treated patients. Maximal immunosuppression produces greater benefits, but may at the same time be associated with unforeseen iatrogenic complications.
3. What significant changes in the immune system take place following ASCT ? Are we really curing autoimmunity ?
No other aspect of the ASCT-based procedures has been the object of so much research, controversy, enthusiasm, and skepticism. A prolonged depression of CD4+ CD45RA cells is a general finding, and takes place following both ASCT and high-dose immunosuppressive therapy (HDIS) alone. The type of immunomodulation which then follows has been called a “black box” by Muraro and Douek [42], but, thanks to their own and others’ investigations, is becoming increasingly clear. High-dose immunosuppression reduces the population of autoimmune cells to minimal residual autoimmune disease (MRAD). While the cure of oncohematological disease requires the eradication of cancer SC, a different view is entertained for ADs. Two basic mechanisms have been postulated.The first has been defined as a “re-education” of the faulty immune system [1], obtained by restoring a diverse antigen-specific repertoire through reactivation of the thymic output (“thymic rebound”), which has also been shown to persist in adults, albeit in lesser measure. In a recent study of ASCT in 7 SLE patients the Berlin group has found evidence for an overwhelming regeneration of the adoptive immune system and of the B-cell lineage, which became apparently tolerant to self-antigens [3]. The second mechanism is closely related, and consists in the reconstitution of the regulatory T-cell pool following ASCT. Tregs (CD4+ CD25+) expressing the transcription factor Foxp3 are crucial in preventing autoreactivity and restraining autoimmunity throughout life. Experimental and clinical studies have demonstrated the impact of the T regulatory network in inducing post-transplant immune tolerance in SLE [63].
Are these changes sufficient and stable enough to guarantee a rebuilding of the immune system, configured in a way that is less likely to redevelop autoimmunity? The abundant and sophisticated studies undeniably display some controversies. In a first study in autotransplanted MS patients the T cells recognizing myelin basic protein were indeed initially depleted by immunoablation, but then rapidly expanded from the reconstituted T cell repertoire in 12 months [52]. More recently, an early recovery of CD4 T-cell receptor diversity was found after “lymphoablative” conditioning and autologous CD34 cell transplantation in systemic sclerosis (SSc) patients, suggesting that the treatment is not completely T-cell ablative (or, more generally immune SC-ablative), and thus not ultimately curative [51]. This contrasts with another recent study which found that CD34+-selected progenitor cells had limited survival capacity and are therefore unlikely to be a major source of carryover of autoimmune T-cell expansions [11]. However, in a comprehensive recent study analyzing original and pooled data from autotransplanted MS patients, Mondria et al [40] found not only the previously known persistence of CSF oligoclonal bands in 88% of the reported cases, but also the persistence of the soluble lymphocyte activator CD27 – thus concluding that complete eradication of activated lymphocytes from the CNS had not been established, despite an intensive immunosuppressive regimen including ATG, CY and total body irradiation (TBI), in two fractions of 5 Gy a day at days –2 and –1. Active demyelinization and axonal damage have been found to continue after ASCT [39]. Our own clinical experience has included late (and very late) relapses, in a way that suggested a recapitulation of the natural history of lupus. So whether pressing the reset button will turn out to be immunologically curative is still uncertain.
4. What type of benefit, if any, does ASCT confer to severe, progressive, relapsing-refractory ADs?
In a recent, provocative editorial commenting on the utilization of ASCT for SADs, and more specifically for the rheumatic diseases, Illei [23] has posed the question, whether “the glass is half full or half empty”.
The effects of ASCT may be divided into two phases: the early suppression of ongoing, immuno-inflammatory events, and the later resetting of the autoimmune clock, which is closely related to the length and grade of remission. The first effect is clearly due to the immunosuppressive conditioning regimens, and is proportional to the dose intensity, and also independent from HSC rescue. No sophisticated dynamics occur here, besides the well-known combination of immunosuppression and abrogation of its attending inflammation. This first effect is responsible for its dramatic disease-arresting (“nosostatic”) properties, which have been observed in practically all actively aggressive SADs, and most demonstratively in SLE. This change occurs in the aggressive phases of disease, where ASCT may well be the most potent salvage therapy available. A clear distinction of the diverse sensitivity to ASCT according to the phases of disease has been recently made by Shevchenko et al [49], who have divided the transplant strategies for MS into “early”, “conventional” and “salvage-late” procedures. Among the many examples of this early, dramatic therapeutic effect are, besides the cancellation of systemic symptoms, the almost immediate clearance of inflammatory urinary sediments in lupus nephritis, the rapid improvement of nailfold capillaroscopy in SSc [4], and the early abrogation of Gadolinium-enhancing lesions in MS [27]. The striking disappearance of diffuse calcinosis in a child with overlap connective disease [13] and the regression of dermal fibrosis in patients with severe scleroderma [43] may be considered intermediate changes.
The impact of ASCT on SADs in the long run has been discussed in several contributions. In the most important study, Progression Free Survival (PFS), which may be considered as the most accurate estimated outcome of a therapeutic procedure, was 43% at 3 years [14]. Three apparently contrasting aspects emerge: first, that in the overwhelming majority of patients no authentic immunological cure may be realistically expected; second, that dramatic remissions occur, may be life-saving, and even long term. Thirdly, in most relapses the utilization of conventional therapies, to which the patients were formerly refractory, is generally possible.
5. Is ASCT the best available treatment for SADs?
ASCT is a powerful therapeutic procedure for SADs. But can it be regarded as the best treatment available, considering the increasing utilization of new pharmacological, prospective (phase III) clinical trials, which are being actively pursued for SSc (the ASTIS trial in Europe and the SCOT trial in North America), MS (ASTIMS, which is probably the most advanced one), Crohn’s disease (ASTIC), and SLE (ASTIL)? It is clear that this is the only way to obtain a scientifically correct answer. However, the pace of medical progress is such, that by the time that these laborious trials will have reached statistical significance, new agents may have superseded those utilized in the non-transplant arms. Furthermore, in a sizable proportion of these patients' ASCT may be integrated with other therapeutic interventions, including high-dose immunoglobulins (HDIG), biologics and possibly new, “intelligent” molecules.
Allogeneic transplantation facts and questions
More cogently than for the autologous procedure, animal experiments and results from coincidental disease patients had indicated a powerful instrument to cure autoimmunity in Allo-SCT. In an international workshop held in 2005, it was stated that “the potential for a 1-time delivery of a curative therapy is outstanding” [17]. But will it really be so? Many clinical trials are being pursued worldwide, but I shall confine myself only to published material and our personal experience.
Clinical results
A retrospective EBMT study [10] has collected 35 patients having received 38 allogeneic transplants for various ADs, hematological and non-hematological. The donors were identical siblings for 24 patients, matched unrelated donors (MUD) for 3, mismatched related for 2 and syngeneic for 3 patients. Treatment related mortality (TRM) was 22.1% at 2 years and 30.7 at 5, while death due to progression of disease was 3.2% at 2 years and 8.7% at 5. Of the 29 surviving patients 55% achieved complete clinical and laboratory remission, and 24% achieved a partial remission. The consensus is that nonmyeloablative (NST), reduced intensity conditioning regimens (RIC) should be utilized [46].
Immunological aspects
The substitution of an immune system which is behaving badly by a normal, healthy one is the rationale of the allogeneic approach, and its successful achievement is the prerequisite for embarking on a treatment which has been saddled with a 30% mortality after 5 years [17]. Although it is predictable that TRM following Allo-SCT, if further pursued, will probably become lower, both with an improvement of the learning curve and with optimized conditioning regimens, and effective GVHD control, the only legitimate motivation for performing it is achieving a cure.Allo-SCT is traditionally regarded as a “platform for immunotherapy” [24]. An exhaustive analysis of the mechanisms by which it might cure ADs has been performed by Sykes and Nikolic [53], who have placed the previously discussed GVA effect in the foreground. A retrospective study showed, in analogy to an established pattern in oncohematological diseases, that there were more relapses of coincidental ADs in patients transplanted for hematological malignancies with no GVHD, than in those who developed it [19]. However this effect could not be detected in the recent EBMT study [10], and a much greater clinical material would be necessary to obtain significant evidence.Efforts have been made, as already attempted in oncohematological diseases, to separate GVHD from GVA. A potent GVA effect was demonstrated in rat models of EAE. Clinically there is a group of patients who had been allotransplanted for SADs, in whom donor lymphocyte infusions (DLI) were necessary to achieve full donor chimerism, which ultimately ensured complete remissions of the SADs (lit in 11). These results are counterbalanced with others, which are in favor of the hypothesis that mixed chimerism might be capable of inducing long-term remissions [7]. However it has been shown that increasing mixed chimerism is conducive to graft loss in children transplanted for non-malignant disorders [45]. Full chimerism was present in two patients with rheumatoid arthritis [26] and in a 7-year old boy with Evans syndrome, in whom two autologous transplants had been previously unsuccessful [57].
Controversial evidence, however, comes from the analysis of relapsed patients. There appear to be two types of relapses. An example of the first type is the report of a failure of Allo-SCT to arrest disease activity in a patient with MS having been successfully transplanted because of coincidental chronic myeloid leukemia [38]. Even more disquieting are the aforementioned reports of patients with SADs having received Allo-SCT, but having subsequently relapsed despite full donor chimerism. The first and widely acknowledged case was a female patient with rheumatoid arthritis (RA), who received an HLA-identical transplant because of gold-induced aplastic anemia [55] and the second another patient with RA and multiple myeloma (MM), in whom the myeloma was cured but the RA relapsed [31]. The most demonstrative case is the one of a patient with severe Evans syndrome, who was transplanted from his HLA-identical sister but needed a series of DLI in order to achieve full donor chimerism and complete hematological remission. This patient unfortunately relapsed and died with a terminal hemolytic-uremic syndrome 5 years later [20]. The patient was male and had received the bone marrow of his HLA-identical sister. The immunoglobulins (IgG, IgM) eluted from his 100% XX expanded B cells were not the ones eluted from his Coombs-positive cells. It was hypothesized that the autoantibodies might have been secreted by long-lived host plasmacytes surviving in postulated marrow niches [18]. Even allowing for the hypothesis that relapses in donor cells in patients transplanted for leukemia might be less uncommon than generally thought to be, it is still an extremely rare event, having been identified in 14 out of 10,489 transplants in a recent survey [37]. In contrast, 3 relapses in the much smaller group of autoimmune allotransplanted patients inevitably causes some perplexity. Only further careful investigations will hopefully elucidate this unexpected problem.
Syngeneic transplants are a niche event. Three patients with RA received syngeneic transplants following high-dose immunosuppression. The first was a patient with severe seronegative RA, who enjoyed a long-term remission [59]. However a second patient with progressively erosive, rheumatoid factor positive RA, who was treated with high-dose CY and received an unmanipulated peripheral blood graft (PBSCT) from her identical twin sister, had a poor clinical response, associated with serological persistence64. A still unpublished case is the one of 45 year old lady with severe seropositive RA who was transplanted in Genoa from her identical twin sister on July 29, 2005. The conditioning regimen consisted of CY, 160 mg/Kg. Both rheumatoid factor and anti-cyclic citrulline peptide (CCP) titres decreased significantly (CCP from 234 to 2), but there was a clinical relapse with fever, polyarthritis and elevation of ESR, requiring further treatment.
Concluding remarks
Is there, at the time of this writing, sufficient evidence to answer the question, as to whether HSCT, in its various paradigms, is and will be the best available therapy for SADs? There has been a tendency to place the cause of autoimmunity on a faulty immune system, thus assimilating ADs to the neoplastic lymphoproliferative diseases. However most ADs result from a combination of faulty immune systems and antigen (target organ) dysfunctions. The distinction between primary and secondary ADs, the first being sustained by primary immune defaults and the latter by a predominant antigenic trigger, has been considered as helpful for the evaluation of SCT interventions. However the interaction between immune system and target organ antigenicity is extremely tight.
The autologous procedure is being performed worldwide because of its combination of safety and efficacy. It is capable of arresting progressive, otherwise refractory ADs. In addition, if utilized early in appropriate patients, it favorably changes the course of disease, even allowing for varying degrees of regeneration. Whether the autoaggressive immune system is being re-educated or, more simply, reset, is still not fully clarified. With this background, I believe that Illei’s glass [39] is more full than empty, when ASCT is performed in an early stage of disease (fig. 1). However , independently from the results, I believe that there ultimately will be an integration between the two approaches, with careful selection of individual patients.
A word of caution must be said concerning the potential development not only of PML, as already discussed, but also of therapy-related myelodysplasia and leukemia (t-MDS, t-AML), which must be closely watched for when utilizing alkylating drugs and others. Fortunately, there haven’t been such reports in this area, and recourse to ASCT in patients with SADs should not be hindered by the fear of late malignant complications, although careful long-term surveillance is mandatory.
Great expectations have been associated with allogeneic SCT, but its position is still uncertain. Ongoing trials will hopefully offer some answers to the question, or hope, whether the total eradication of a faulty immune system will be sufficient, and whether there is solid evidence of a clinically exploitable GVA effect. The unexpected relapses despite full donor chimerism are still a problem, but further experience is needed.
Summary
Two different sets of investigation are at the origin of hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The experimental evidence consisted in the transfer/cure of animal SADs as murine lupus by means of allogeneic but also, almost paradoxically, autologous HSCT. The clinical arm comes from serendipitous reports of patients allotransplanted for coincidental diseases, and finally cured of both conditions. The encouraging results of ASCT in experimental ADs were enthusiastically translated into human therapy by clinicians hoping to achieve great results without incurring into the rigors associated with the allogeneic procedure.
Well over 1000 ASCT for SADs have been performed worldwide at this time with multiple sclerosis (MS) and connective tissue diseases in the foreground. Transplant-related mortality (TRM) and morbidity have decreased to well under 5%. A dramatic disease-arresting effect is a constant benefit, but the whole course of the disease appears to be influenced favorably. Profound changes of the autoimmune circuitry have been demonstrated, but no authentic eradication of disease (cure?) should realistically be expected. Important multicentric prospective trials are ongoing to compare ASCT to the best available non-transplant therapies, but it may be argued that in the end both approaches will be integrated for single patients, and that new agents will possibly alter present strategies.
Allogeneic STC is eliciting great expectations, but the burden of higher mortality and morbidity with GVHD in the first place, must be considered, even when making recourse to reduced conditioning regimens (RIC). Paradoxical relapses despite complete donor chimerism have been reported. Further experience is clearly needed, but the early enthusiasm for an attractive one-shot therapy must be tempered with a realistic evaluation, at least until new significant breakthroughs have been attained.
Acknowledgements
This article is based on the materials of the perspective article in the International Journal of Clinical Rheumatology 2009; 4(4):395-408.
References
1. Abrahamsson S, Muraro PA. Immune re-education following autologous stem cell transplantation. Autoimmunity. 2008;41:577-584. doi: 10.1080/08916930802197081.
2. Alderuccio F, Chan J, Ban-Hock T. Tweaking the immune system: Gene therapy-assisted autologous haematopoietic stem cell transplantation as a treatmemnt for autoimmune diseases. Autoimmunity. 2008;41:679-685. doi: 10.1080/08916930802197123.
4. Aschwanden M, Daikeler T, Jeager KA, et al. Rapid improvement of nailfold capillaroscopy after intense immunosuppression for systemic sclerosis and mixed connective tissue disease. Ann Rheum Dis. 2008;67:1057-1059.
5. Brodsky RA and Jones R. Intensive immunosuppression with high dose cyclophosphamide but without stem cell rescue for severe autoimmunity: Advantages and disadvantages. Autoimmunity. 2008;41:596-600. doi: 10.1080/08916930802197206.
11. Dubinsky AN, Burt RK, Martin R, Muraro PA. T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant. 2009;43:1-7. doi: 10.1038/bmt.2009.139.
19. Hinterberger W, Hinterberger-Fischer M, Marmont AM. Clinically demonstrable anti-autoimmunity mediated by allogeneic immune cells favourably affects outcome after stem cell transplantation in human autoimmune diseases. Bone Marrow Transplant. 2002;30:753-759.
20. Hoyer BE, Manz RA, Radbruch A, Hiepe F. Long-lived plasma cells and their contribution to autoimmunity. Ann NY Acad Sci. 2005;1050:124-33. doi: 10.1196/annals.1313.014.
21. Ikehara S. A novel method of bone marrow transplantation [BMT] for intractable autoimmune diseases. J Autoimmunity. 2008;30:108-115.
22. Ikehara S. Treatment of autoimmune diseases by hematopoietic bone marrow transplantation. Exp Hematol. 2001;29:661-669.
25. Le Blanc K, Frassoni F, Ball I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe acute graft-versus-host disease. A phase II study. Lancet. 2008;371:1579-1586. doi: 10.1016/S0140-6736(08)60690-X.
26. Lowenthal R, Francis H, Gill D. Twenty-year remission of rheumatoid arthritis in 2 patients after allogeneic bone marrow transplant. J Rheumatol. 2006;33:812-813.
27. Mancardi GL, Saccardi R, Filippi M, et al. Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology. 2001;57:62-68.
28. Marmont AM [Guest Editor]. Hematopoietic stem cell transplantation in autoimmune diseases. Autoimmunity. 2008;41:556-690.
29. Marmont AM and Burt RK. Hematopoietic stem cell transplantation for systemic lupus erythematosus, the antiphospholipid syndrome and bullous skin disorders. Autoimmunity. 2008;41:639-647. doi: 10.1080/08916930802198345.
30. Marmont AM, Gratwohl A, Vischer T and Tyndall A. Haemopoietic precursor cell transplants for autoimmune diseases. Lancet. 1995;345:978.
31. Marmont AM, Gualandi F, Occhini D, et al. Catastrophic relapse of Evans syndrome five years after allogeneic BMT notwithstanding full donor chimerism. Terminal hemolytic-uremic syndrome. Autoimmunity. 2006;39:505-511. doi: 10.1080/08916930600847598.
32. Marmont AM, van Lint MT, Gualandi F and Bacigalupo A. Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. Lupus. 1997;6:545-548.
33. Marmont AM. Coincidental autoimmune disease in patients transplanted for conventional indications. Best Practice Research Clin Haematol. 2004;17:223-232. doi: 10.1016/j.beha.2004.04.004.
34. Marmont AM. Historical perspective and rationale of HSCT for autoimmune diseases. In Burt RK, Marmont AM [eds]: Stem cell therapy for autoimmune diseases. Landes Bioscience, Georgetown, 2004.
35. Marmont AM. Is there any evidence of a graft-versus autoimmunity effect in allogeneic transplantation? Blood Marrow Transplant Rev. 2004;4:11.
36. Marmont AM. Perspective: immunoablation with stem cell rescue: a possible cure for systemic lupus erythematosus? Lupus. 1993;2:151-156.
37. McColl G, Koshaka H, Wicks I. High-dose chemotherapy and syngeneic hemopoietic stem cell transplantation for severe seronegative rheumatoid arthritis. Ann Intern Med. 1999;131:550-3.
38. McKendry RJ, Huebsch L and Leclair B. Progression of rheumatoid arthritis following bone marrow transplantation: a case report with a 13 year follow-up. Arthritis Rheum. 1996;39:1246-53.
40. Mondria T, Lamers CH, te Bockhorst PA, et al. Bone marrow transplantation fails to halt intrathecal lymphocyte actrivation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2008;79:1013-1015. doi: 10.1136/jnnp.2007.133520.
42. Muraro P, Douek DC. Renewing the T-cell repertoire to arrest autoimmune aggression. Trends Immunol. 2006;27:61-67. doi: 10.1016/j.it.2005.12.003.
47. Saccardi R and Gualandi F. Hematopoietic stem cell transplantation procedures. Autoimmunity. 2008;41:570-576. doi: 10.1080/08916930802197776.
48. Saccardi R, Di Gioia M and Bosi A. Haematopoietic stem cell transplantation for autoimmune disorders. Current Opinion Hematol. 2008;594-600.
49. Shevchenko YL, Novik AA, Kuznetsov AN, et al. High dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol. 2008;36:922-928. doi: 10.1016/j.exphem.2008.03.001.
52. Sun W, Popat V, Hutton G, et al. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell graft in multiple sclerosis. Brain. 2004;127:996-1008.
56. Uccelli A, Mancardi GL and Chiesa S. Is there a role for mesenchymal stem cells in autoimmune diseases? Autoimmunity. 2008;41:392-395. doi:10.1080/08916930802200166.
57. Urban C, Lackner H, Sovinz P, et al. Succesful unrelated cord blood transplantation in a 7- year old boy with Evans syndrome refractory to immunosuppression and double autologous stem cell transplantation. Eur J Haematol. 2006;76:326-330. doi: 10.1111/j.0902-4441.2006.t01-1-EJH2549.x.
58. van Bekkum DW. Stem cell transplantation for autoimmune disorders. Preclinical experiments. Best Practice & Research Clin Haematol. 2004;17:201-222. doi:10.1016/j.beha.2004.04.003.
59. van Oosterhout M, Verburg RJ, Levahrt EW, et al. High dose chemotherapy and syngeneic stem cell transplantation in a patient with refractory rheumatoid arthritis: poor response associated with persistence of host antibodies and synovial abnormalities. Ann Rheum Dis. 2005;64:1783-5. doi: 10.1136/ard.2004.034793.
60. van Wijmeersch B, Spranger B, Rutgeers O, et al. Allogeneic bone marrow transplantation in models of experimental autoimmune encephalomyelitis: evidence for a Graft-versus-Autoimmunity effect. Biol Blood Marrow Transplant. 2007;13:627-637. doi: 10.1016/j.bbmt.2007.03.001.
61. Voltarelli JC, Couri CE, Stracieri AB, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type I diabetes mellitus. JAMA. 2007;297:1568-1576. doi:10.1001/jama.297.14.1568.
62. Young N, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108:2509-2518. 10.1182/blood-2006-03-010777.
63. Zhang L, Bertucci AM, Ramsey-Goldman R, Burt RK, et al. Regulatory T cell (treg) subset return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remisison of lupus. J Immunol. 2009;183:6346-6358. doi: 10.4049/jimmunol.0901773.
Introduction
Stem cell therapy for severe autoimmune diseases (AD), generally as hematopoietic stem cell transplantation (HSCT), both allogeneic and autologous, but also more recently as gene therapy-assisted autologous HSCT, has become one of the hottest areas of clinical immunology. It has been developing progressively in the last decades, and has generated “excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature” [6]. The utilization of stem cells to promote regenerative medicine must be distinguished from the purpose of suppressing autoimmune cellular and humoral aggression. This does not mean that both areas aren’t tightly connected, since supplying new pancreatic beta cells to patients with type I diabetes, whether by islet cell transplantation or by boosting their numbers by reprogramming pancreatic acinar cells, cannot resolve the disease if the autoimmune process is not eliminated [61]. In some clinical entities both effects coincide. An appropriate example is aplastic anemia (AA) and some of its minor variants (pure red cell aplasia-PRCA, pure white cell aplasia-PWCA), in which allogeneic HSCT both suppresses autoimmunity and provides new HSC [62]. In all the other autoimmune conditions this double effect has not been demonstrated conclusively.
The utilization of HSCT, overwhelmingly of the autologous modality, has been growing impressively in the last few years, and is still increasing steadily [28, 47]. Autologous HSCT (ASCT) relies on an extensive debulking of the autoaggressive immune system, followed by the re-infusion of the patients’ HSC (commonly identified as CD34+ cells). The allogeneic procedure is based on the substitution of the faulty immune system by a new healthy one, theoretically capable of eradicating the autoimmune clones by means of the classical combination of high-dose immunosuppressive therapy and a Graft-versus-Autoimmunity (GVA) effect, which will be discussed later. Whether this last intervention will be capable of achieving the Holy Grail of self-tolerance [15] is still not established, given the complexity of the pathogenesis of ADs, including the persisting antigenicity of altered “self” proteins [12] and some paradoxical post-transplant relapses despite full donor chimerism, which will be discussed later.
A brief historical recapitulation
Two streams of research, experimental and clinical, are at the origin of the increasing utilization of HSCT, autologous and allogeneic, for SADs [34]. The first animal studies had shown that the transfer of spleen and/or whole marrow cells to immunosuppressed mice could reproduce murine lupus. The culprit cells were shown to be stem or lymphoid progenitors. The next step was to ascertain whether, contrarily, healthy HSC were capable of curing experimental ADs. Human blood SC were capable of suppressing antibody production in lupus mice, perhaps the first demonstration of a curative effect by xenogeneic HSCT. More recently, it has elegantly been shown that the nonmyeloablative transplantation of purified allogeneic HSC not only prevented, but also induced stabilization or reversal of lupus symptoms in NZB mice [50]. Durable mixed chimerism was also efficacious, a point that will be discussed later. A further experimental improvement has been the intra-bone injection of HSC [21].
The resolution of experimental ADs by means of healthy, compatible allo-SCT was to be expected, considering the overwhelming genetic predisposition of inbred strains of mice, which differs from the intricacies of human ADs, in which there is a complex relationship between genetic, environmental and regulatory factors, and where impaired mechanisms of thymic selection interact, in still poorly elucidated ways, with genetic factors. As already mentioned, a GVA effect has been postulated [33], and theoretically dissected in 6 different mechanisms [53], with immune-mediated abrogation of autoreactive clones in the foreground. In practice, donor-derived immune cells are capable of mediating an anti-autoimmune effect either specifically, or as a part of a more general alloimmune reaction. In experimental autoimmune encephalomyelitis (EAE) it was shown that active alloreactivity was associated with the greatest GVA effect [60]. The second stream in favor of allo-SCT came from the clinical observation of patients affected by coincidental diseases, that is patients with ADs having developed a hematologic malignancy for which they received an allo-SCT, and were ultimately cured of both diseases [35]. There were even cases in which allo-BMT transferred the AD of the donor to the recipient, but cured the latter of his former AD.
The rationale for an apparently paradoxical procedure such as autologous HSCT, in which the patients’ immune cells, despite varying degrees of HSC depletion in vitro and/or in vivo, are administered back to them, came from the pioneering studies by van Bekkum and his group, who were able to cure EAE and adjuvant arthritis (AA), both models of human multiple sclerosis (MS) and rheumatoid arthritis (RA), by means of autologous (“pseudoautologous”) HSCT [58]. These results considerably strengthened the philosophy of autologous HSCT for human ADs, even if it was pointed out later that in animal models the abnormality of the antigen-induced type seems to reside in immunocompetent T/B cells but not in the HSC, and therefore ASCT may be curative, while in spontaneous ADs new, unaffected HSC were necessary to achieve a cure [22]. In any case, the utilization of ASCT is now widely accepted for treating severe, refractory ADs.
A powerful immunosuppressive therapy for SADs has been developed at Johns Hopkins University in Baltimore, where such patients are treated with high-dose cyclophosphamide (CY) alone, with an inevitable delay of marrow and blood reconstitution, but with results that do not differ significantly from those obtained by ASCT [5].
Finally, two new approaches appear to be integrating this area. Mesenchymal stem cells (MSC) possess several immunomodulatory properties [44], have been shown to significantly ameliorate Graft-versus-Host Disease [25] (GVHD), and have been considered a valuable therapeutic option for SADs [56]. However the role of this kind of cellular therapy in human AD, whether associated with ASCT or not, is still to be established. Another fascinating approach is based on the idea of achieving antigen-specific tolerance to treat refractory ADs, even if translating such therapies from bench to bedside is still mainly theoretical. An approach combining HSCT and transduction of the culprit self-antigens in autologous HSCs in order to achieve central (thymic) tolerance has been developed by Alderuccio and his group [2], although only in animal experiments with organ-specific autoimmune conditions at this stage.
Autologous transplantation: progress and questions
In contrast to the long interval having taken place between the first allogeneic transplants for animal ADs and translational clinical trials, ASCT quickly followed the experimental investigations. It was proposed by myself for severe SLE in 1993 [36], and then for ADs in general in 1995 [30]. The first transplants were performed for a connective tissue disease [54] and for severe SLE [32]. The following utilization of ASCT for SADs grew almost exponentially, so much so that, besides the continually increasing registered transplants in the EBMT and CIBMTR registries, a recent study by Dominique Farge et al has analyzed 900 patients [14]. Excellent reviews of specific diseases have been published recently, and a monographic issue of Autoimmunity has just been devoted to this theme [28]. Here, I shall focus on the most significant and contemporary questions.
1. Autologous HSCT for ADs has been considered a relatively safe procedure from its inception, but is it becoming safer?
Autoimmune diseases represent an extremely heterogenous spectrum of diseases, and in most of them severe-refractory forms have a poor prognosis and a greatly impaired quality of life. One cannot disagree, however, with Burt’s statement that “Treatment-related mortality needs to be very low for non-malignant diseases”1. Treatment-Related Mortality (TRM) reached 12% in the initial EBMT Registry, decreased to 7 +3% in 2005, and finally did not exceed 5% in the most recent EBMT study [14]. In this last study evidence was also found of a clear center effect, indicating that experienced teams that are well acquainted with the multi-organ involvement of SADs produce superior results. In the case of a single disease such as SLE, a collection of 162 patients transplanted in 30 Centers showed a TRM of 11% [29], However of 200 patients transplanted at Northwestern University, Chicago, the TRM using non-myeloablative conditioning regimens in 200 patients was 1.5% [8]. This does not mean, of course, that TRM cannot grow much higher in very severe conditions such as advanced scleroderma. Scleroderma-related organ disfunction contributed to treatment-related deaths [43]. In conclusion, the answer to this first question is that ASCT may be considered reasonably safe when performed by experienced teams, appropriate conditioning regimens, and on patients who are not too disease-compromised. These data need to be counterbalanced by mortality from disease progression, and require the adoption of inclusion and exclusion criteria for each category of diseases, which cannot be detailed here. Although the inclusion of patients within approved or investigational protocols is the best policy, it must be realized that, in selected patients with advanced, refractory SADs, the decision to perform ASCT will ultimately rely on a combination of clinical acumen, experienced teams, and a good patient-doctor relationship.
2. Which are the most appropriate mobilization and conditioning regimens?
The source of HSCs was initially the bone marrow (BM), but has now changed to the peripheral blood (PB) following mobilization procedures. In the previously mentioned EBMT study of 900 patients the source was PB in 827 cases [43]. The most popular mobilizing regimens generally consist of combinations of cyclophosphamide (CY) and G-CSF [47]. Mobilizing regimens incorporating CY (from 2 to 4g/m2) have the additional, significant advantage of acting as an important therapeutic procedure per se (therapeutic mobilization). In our own experience of 9 SLE patients the achievement of a complete remission (CR) following mobilization with CY 4g/m2 enabled us, in 2 cases, to dispense from performing the initially programmed ASCT.
A variety of conditioning regimens have been utilized, but it could be shown that high-intensity protocols were followed by a lower probability of disease progression, albeit with a higher risk of TRM [16]. The strategy of performing intense immunosuppression without affecting the whole of the hematopoietic system is most generally accepted, taking into account that biologics such as Rituximab have a longer immunosuppressive activity than any chemotherapeutic agent. A combination of both strategies, in which Rituximab 500 mg is given before and after the regular 200 mg/kg CY protocol (the “sandwich technique”), is being currently utilized at Northwestern University, Chicago (USA). Anti-CD20 immunotherapy for the control of relapse following ASCT in patients with rheumatoid arthritis (RA) had been already utilized with success [41], and the strategy of using an additional immunotherapy in this area is attractive. Unfortunately a devastating complication, progressive multifocal leukoencephalopathy (PML), due to the activation of the John Cunningham virus (JCV), has been reported in a disquieting proportion of patients having been immunosuppressed with biological agents (Natalizumab, Rituximab). A recent review reported 52 patients as having developed PML, 7 of which had received HSCT (3 allogeneic, 4 autologous) for lymphoproliferative diseases [9]. Awareness is obviously needed of the potential for PML among Rituximab-treated patients. Maximal immunosuppression produces greater benefits, but may at the same time be associated with unforeseen iatrogenic complications.
3. What significant changes in the immune system take place following ASCT ? Are we really curing autoimmunity ?
No other aspect of the ASCT-based procedures has been the object of so much research, controversy, enthusiasm, and skepticism. A prolonged depression of CD4+ CD45RA cells is a general finding, and takes place following both ASCT and high-dose immunosuppressive therapy (HDIS) alone. The type of immunomodulation which then follows has been called a “black box” by Muraro and Douek [42], but, thanks to their own and others’ investigations, is becoming increasingly clear. High-dose immunosuppression reduces the population of autoimmune cells to minimal residual autoimmune disease (MRAD). While the cure of oncohematological disease requires the eradication of cancer SC, a different view is entertained for ADs. Two basic mechanisms have been postulated.The first has been defined as a “re-education” of the faulty immune system [1], obtained by restoring a diverse antigen-specific repertoire through reactivation of the thymic output (“thymic rebound”), which has also been shown to persist in adults, albeit in lesser measure. In a recent study of ASCT in 7 SLE patients the Berlin group has found evidence for an overwhelming regeneration of the adoptive immune system and of the B-cell lineage, which became apparently tolerant to self-antigens [3]. The second mechanism is closely related, and consists in the reconstitution of the regulatory T-cell pool following ASCT. Tregs (CD4+ CD25+) expressing the transcription factor Foxp3 are crucial in preventing autoreactivity and restraining autoimmunity throughout life. Experimental and clinical studies have demonstrated the impact of the T regulatory network in inducing post-transplant immune tolerance in SLE [63].
Are these changes sufficient and stable enough to guarantee a rebuilding of the immune system, configured in a way that is less likely to redevelop autoimmunity? The abundant and sophisticated studies undeniably display some controversies. In a first study in autotransplanted MS patients the T cells recognizing myelin basic protein were indeed initially depleted by immunoablation, but then rapidly expanded from the reconstituted T cell repertoire in 12 months [52]. More recently, an early recovery of CD4 T-cell receptor diversity was found after “lymphoablative” conditioning and autologous CD34 cell transplantation in systemic sclerosis (SSc) patients, suggesting that the treatment is not completely T-cell ablative (or, more generally immune SC-ablative), and thus not ultimately curative [51]. This contrasts with another recent study which found that CD34+-selected progenitor cells had limited survival capacity and are therefore unlikely to be a major source of carryover of autoimmune T-cell expansions [11]. However, in a comprehensive recent study analyzing original and pooled data from autotransplanted MS patients, Mondria et al [40] found not only the previously known persistence of CSF oligoclonal bands in 88% of the reported cases, but also the persistence of the soluble lymphocyte activator CD27 – thus concluding that complete eradication of activated lymphocytes from the CNS had not been established, despite an intensive immunosuppressive regimen including ATG, CY and total body irradiation (TBI), in two fractions of 5 Gy a day at days –2 and –1. Active demyelinization and axonal damage have been found to continue after ASCT [39]. Our own clinical experience has included late (and very late) relapses, in a way that suggested a recapitulation of the natural history of lupus. So whether pressing the reset button will turn out to be immunologically curative is still uncertain.
4. What type of benefit, if any, does ASCT confer to severe, progressive, relapsing-refractory ADs?
In a recent, provocative editorial commenting on the utilization of ASCT for SADs, and more specifically for the rheumatic diseases, Illei [23] has posed the question, whether “the glass is half full or half empty”.
The effects of ASCT may be divided into two phases: the early suppression of ongoing, immuno-inflammatory events, and the later resetting of the autoimmune clock, which is closely related to the length and grade of remission. The first effect is clearly due to the immunosuppressive conditioning regimens, and is proportional to the dose intensity, and also independent from HSC rescue. No sophisticated dynamics occur here, besides the well-known combination of immunosuppression and abrogation of its attending inflammation. This first effect is responsible for its dramatic disease-arresting (“nosostatic”) properties, which have been observed in practically all actively aggressive SADs, and most demonstratively in SLE. This change occurs in the aggressive phases of disease, where ASCT may well be the most potent salvage therapy available. A clear distinction of the diverse sensitivity to ASCT according to the phases of disease has been recently made by Shevchenko et al [49], who have divided the transplant strategies for MS into “early”, “conventional” and “salvage-late” procedures. Among the many examples of this early, dramatic therapeutic effect are, besides the cancellation of systemic symptoms, the almost immediate clearance of inflammatory urinary sediments in lupus nephritis, the rapid improvement of nailfold capillaroscopy in SSc [4], and the early abrogation of Gadolinium-enhancing lesions in MS [27]. The striking disappearance of diffuse calcinosis in a child with overlap connective disease [13] and the regression of dermal fibrosis in patients with severe scleroderma [43] may be considered intermediate changes.
The impact of ASCT on SADs in the long run has been discussed in several contributions. In the most important study, Progression Free Survival (PFS), which may be considered as the most accurate estimated outcome of a therapeutic procedure, was 43% at 3 years [14]. Three apparently contrasting aspects emerge: first, that in the overwhelming majority of patients no authentic immunological cure may be realistically expected; second, that dramatic remissions occur, may be life-saving, and even long term. Thirdly, in most relapses the utilization of conventional therapies, to which the patients were formerly refractory, is generally possible.
5. Is ASCT the best available treatment for SADs?
ASCT is a powerful therapeutic procedure for SADs. But can it be regarded as the best treatment available, considering the increasing utilization of new pharmacological, prospective (phase III) clinical trials, which are being actively pursued for SSc (the ASTIS trial in Europe and the SCOT trial in North America), MS (ASTIMS, which is probably the most advanced one), Crohn’s disease (ASTIC), and SLE (ASTIL)? It is clear that this is the only way to obtain a scientifically correct answer. However, the pace of medical progress is such, that by the time that these laborious trials will have reached statistical significance, new agents may have superseded those utilized in the non-transplant arms. Furthermore, in a sizable proportion of these patients' ASCT may be integrated with other therapeutic interventions, including high-dose immunoglobulins (HDIG), biologics and possibly new, “intelligent” molecules.
Allogeneic transplantation facts and questions
More cogently than for the autologous procedure, animal experiments and results from coincidental disease patients had indicated a powerful instrument to cure autoimmunity in Allo-SCT. In an international workshop held in 2005, it was stated that “the potential for a 1-time delivery of a curative therapy is outstanding” [17]. But will it really be so? Many clinical trials are being pursued worldwide, but I shall confine myself only to published material and our personal experience.
Clinical results
A retrospective EBMT study [10] has collected 35 patients having received 38 allogeneic transplants for various ADs, hematological and non-hematological. The donors were identical siblings for 24 patients, matched unrelated donors (MUD) for 3, mismatched related for 2 and syngeneic for 3 patients. Treatment related mortality (TRM) was 22.1% at 2 years and 30.7 at 5, while death due to progression of disease was 3.2% at 2 years and 8.7% at 5. Of the 29 surviving patients 55% achieved complete clinical and laboratory remission, and 24% achieved a partial remission. The consensus is that nonmyeloablative (NST), reduced intensity conditioning regimens (RIC) should be utilized [46].
Immunological aspects
The substitution of an immune system which is behaving badly by a normal, healthy one is the rationale of the allogeneic approach, and its successful achievement is the prerequisite for embarking on a treatment which has been saddled with a 30% mortality after 5 years [17]. Although it is predictable that TRM following Allo-SCT, if further pursued, will probably become lower, both with an improvement of the learning curve and with optimized conditioning regimens, and effective GVHD control, the only legitimate motivation for performing it is achieving a cure.Allo-SCT is traditionally regarded as a “platform for immunotherapy” [24]. An exhaustive analysis of the mechanisms by which it might cure ADs has been performed by Sykes and Nikolic [53], who have placed the previously discussed GVA effect in the foreground. A retrospective study showed, in analogy to an established pattern in oncohematological diseases, that there were more relapses of coincidental ADs in patients transplanted for hematological malignancies with no GVHD, than in those who developed it [19]. However this effect could not be detected in the recent EBMT study [10], and a much greater clinical material would be necessary to obtain significant evidence.Efforts have been made, as already attempted in oncohematological diseases, to separate GVHD from GVA. A potent GVA effect was demonstrated in rat models of EAE. Clinically there is a group of patients who had been allotransplanted for SADs, in whom donor lymphocyte infusions (DLI) were necessary to achieve full donor chimerism, which ultimately ensured complete remissions of the SADs (lit in 11). These results are counterbalanced with others, which are in favor of the hypothesis that mixed chimerism might be capable of inducing long-term remissions [7]. However it has been shown that increasing mixed chimerism is conducive to graft loss in children transplanted for non-malignant disorders [45]. Full chimerism was present in two patients with rheumatoid arthritis [26] and in a 7-year old boy with Evans syndrome, in whom two autologous transplants had been previously unsuccessful [57].
Controversial evidence, however, comes from the analysis of relapsed patients. There appear to be two types of relapses. An example of the first type is the report of a failure of Allo-SCT to arrest disease activity in a patient with MS having been successfully transplanted because of coincidental chronic myeloid leukemia [38]. Even more disquieting are the aforementioned reports of patients with SADs having received Allo-SCT, but having subsequently relapsed despite full donor chimerism. The first and widely acknowledged case was a female patient with rheumatoid arthritis (RA), who received an HLA-identical transplant because of gold-induced aplastic anemia [55] and the second another patient with RA and multiple myeloma (MM), in whom the myeloma was cured but the RA relapsed [31]. The most demonstrative case is the one of a patient with severe Evans syndrome, who was transplanted from his HLA-identical sister but needed a series of DLI in order to achieve full donor chimerism and complete hematological remission. This patient unfortunately relapsed and died with a terminal hemolytic-uremic syndrome 5 years later [20]. The patient was male and had received the bone marrow of his HLA-identical sister. The immunoglobulins (IgG, IgM) eluted from his 100% XX expanded B cells were not the ones eluted from his Coombs-positive cells. It was hypothesized that the autoantibodies might have been secreted by long-lived host plasmacytes surviving in postulated marrow niches [18]. Even allowing for the hypothesis that relapses in donor cells in patients transplanted for leukemia might be less uncommon than generally thought to be, it is still an extremely rare event, having been identified in 14 out of 10,489 transplants in a recent survey [37]. In contrast, 3 relapses in the much smaller group of autoimmune allotransplanted patients inevitably causes some perplexity. Only further careful investigations will hopefully elucidate this unexpected problem.
Syngeneic transplants are a niche event. Three patients with RA received syngeneic transplants following high-dose immunosuppression. The first was a patient with severe seronegative RA, who enjoyed a long-term remission [59]. However a second patient with progressively erosive, rheumatoid factor positive RA, who was treated with high-dose CY and received an unmanipulated peripheral blood graft (PBSCT) from her identical twin sister, had a poor clinical response, associated with serological persistence64. A still unpublished case is the one of 45 year old lady with severe seropositive RA who was transplanted in Genoa from her identical twin sister on July 29, 2005. The conditioning regimen consisted of CY, 160 mg/Kg. Both rheumatoid factor and anti-cyclic citrulline peptide (CCP) titres decreased significantly (CCP from 234 to 2), but there was a clinical relapse with fever, polyarthritis and elevation of ESR, requiring further treatment.
Concluding remarks
Is there, at the time of this writing, sufficient evidence to answer the question, as to whether HSCT, in its various paradigms, is and will be the best available therapy for SADs? There has been a tendency to place the cause of autoimmunity on a faulty immune system, thus assimilating ADs to the neoplastic lymphoproliferative diseases. However most ADs result from a combination of faulty immune systems and antigen (target organ) dysfunctions. The distinction between primary and secondary ADs, the first being sustained by primary immune defaults and the latter by a predominant antigenic trigger, has been considered as helpful for the evaluation of SCT interventions. However the interaction between immune system and target organ antigenicity is extremely tight.
The autologous procedure is being performed worldwide because of its combination of safety and efficacy. It is capable of arresting progressive, otherwise refractory ADs. In addition, if utilized early in appropriate patients, it favorably changes the course of disease, even allowing for varying degrees of regeneration. Whether the autoaggressive immune system is being re-educated or, more simply, reset, is still not fully clarified. With this background, I believe that Illei’s glass [39] is more full than empty, when ASCT is performed in an early stage of disease (fig. 1). However , independently from the results, I believe that there ultimately will be an integration between the two approaches, with careful selection of individual patients.
A word of caution must be said concerning the potential development not only of PML, as already discussed, but also of therapy-related myelodysplasia and leukemia (t-MDS, t-AML), which must be closely watched for when utilizing alkylating drugs and others. Fortunately, there haven’t been such reports in this area, and recourse to ASCT in patients with SADs should not be hindered by the fear of late malignant complications, although careful long-term surveillance is mandatory.
Great expectations have been associated with allogeneic SCT, but its position is still uncertain. Ongoing trials will hopefully offer some answers to the question, or hope, whether the total eradication of a faulty immune system will be sufficient, and whether there is solid evidence of a clinically exploitable GVA effect. The unexpected relapses despite full donor chimerism are still a problem, but further experience is needed.
Summary
Two different sets of investigation are at the origin of hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The experimental evidence consisted in the transfer/cure of animal SADs as murine lupus by means of allogeneic but also, almost paradoxically, autologous HSCT. The clinical arm comes from serendipitous reports of patients allotransplanted for coincidental diseases, and finally cured of both conditions. The encouraging results of ASCT in experimental ADs were enthusiastically translated into human therapy by clinicians hoping to achieve great results without incurring into the rigors associated with the allogeneic procedure.
Well over 1000 ASCT for SADs have been performed worldwide at this time with multiple sclerosis (MS) and connective tissue diseases in the foreground. Transplant-related mortality (TRM) and morbidity have decreased to well under 5%. A dramatic disease-arresting effect is a constant benefit, but the whole course of the disease appears to be influenced favorably. Profound changes of the autoimmune circuitry have been demonstrated, but no authentic eradication of disease (cure?) should realistically be expected. Important multicentric prospective trials are ongoing to compare ASCT to the best available non-transplant therapies, but it may be argued that in the end both approaches will be integrated for single patients, and that new agents will possibly alter present strategies.
Allogeneic STC is eliciting great expectations, but the burden of higher mortality and morbidity with GVHD in the first place, must be considered, even when making recourse to reduced conditioning regimens (RIC). Paradoxical relapses despite complete donor chimerism have been reported. Further experience is clearly needed, but the early enthusiasm for an attractive one-shot therapy must be tempered with a realistic evaluation, at least until new significant breakthroughs have been attained.
Acknowledgements
This article is based on the materials of the perspective article in the International Journal of Clinical Rheumatology 2009; 4(4):395-408.
References
1. Abrahamsson S, Muraro PA. Immune re-education following autologous stem cell transplantation. Autoimmunity. 2008;41:577-584. doi: 10.1080/08916930802197081.
2. Alderuccio F, Chan J, Ban-Hock T. Tweaking the immune system: Gene therapy-assisted autologous haematopoietic stem cell transplantation as a treatmemnt for autoimmune diseases. Autoimmunity. 2008;41:679-685. doi: 10.1080/08916930802197123.
4. Aschwanden M, Daikeler T, Jeager KA, et al. Rapid improvement of nailfold capillaroscopy after intense immunosuppression for systemic sclerosis and mixed connective tissue disease. Ann Rheum Dis. 2008;67:1057-1059.
5. Brodsky RA and Jones R. Intensive immunosuppression with high dose cyclophosphamide but without stem cell rescue for severe autoimmunity: Advantages and disadvantages. Autoimmunity. 2008;41:596-600. doi: 10.1080/08916930802197206.
11. Dubinsky AN, Burt RK, Martin R, Muraro PA. T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant. 2009;43:1-7. doi: 10.1038/bmt.2009.139.
19. Hinterberger W, Hinterberger-Fischer M, Marmont AM. Clinically demonstrable anti-autoimmunity mediated by allogeneic immune cells favourably affects outcome after stem cell transplantation in human autoimmune diseases. Bone Marrow Transplant. 2002;30:753-759.
20. Hoyer BE, Manz RA, Radbruch A, Hiepe F. Long-lived plasma cells and their contribution to autoimmunity. Ann NY Acad Sci. 2005;1050:124-33. doi: 10.1196/annals.1313.014.
21. Ikehara S. A novel method of bone marrow transplantation [BMT] for intractable autoimmune diseases. J Autoimmunity. 2008;30:108-115.
22. Ikehara S. Treatment of autoimmune diseases by hematopoietic bone marrow transplantation. Exp Hematol. 2001;29:661-669.
25. Le Blanc K, Frassoni F, Ball I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe acute graft-versus-host disease. A phase II study. Lancet. 2008;371:1579-1586. doi: 10.1016/S0140-6736(08)60690-X.
26. Lowenthal R, Francis H, Gill D. Twenty-year remission of rheumatoid arthritis in 2 patients after allogeneic bone marrow transplant. J Rheumatol. 2006;33:812-813.
27. Mancardi GL, Saccardi R, Filippi M, et al. Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology. 2001;57:62-68.
28. Marmont AM [Guest Editor]. Hematopoietic stem cell transplantation in autoimmune diseases. Autoimmunity. 2008;41:556-690.
29. Marmont AM and Burt RK. Hematopoietic stem cell transplantation for systemic lupus erythematosus, the antiphospholipid syndrome and bullous skin disorders. Autoimmunity. 2008;41:639-647. doi: 10.1080/08916930802198345.
30. Marmont AM, Gratwohl A, Vischer T and Tyndall A. Haemopoietic precursor cell transplants for autoimmune diseases. Lancet. 1995;345:978.
31. Marmont AM, Gualandi F, Occhini D, et al. Catastrophic relapse of Evans syndrome five years after allogeneic BMT notwithstanding full donor chimerism. Terminal hemolytic-uremic syndrome. Autoimmunity. 2006;39:505-511. doi: 10.1080/08916930600847598.
32. Marmont AM, van Lint MT, Gualandi F and Bacigalupo A. Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. Lupus. 1997;6:545-548.
33. Marmont AM. Coincidental autoimmune disease in patients transplanted for conventional indications. Best Practice Research Clin Haematol. 2004;17:223-232. doi: 10.1016/j.beha.2004.04.004.
34. Marmont AM. Historical perspective and rationale of HSCT for autoimmune diseases. In Burt RK, Marmont AM [eds]: Stem cell therapy for autoimmune diseases. Landes Bioscience, Georgetown, 2004.
35. Marmont AM. Is there any evidence of a graft-versus autoimmunity effect in allogeneic transplantation? Blood Marrow Transplant Rev. 2004;4:11.
36. Marmont AM. Perspective: immunoablation with stem cell rescue: a possible cure for systemic lupus erythematosus? Lupus. 1993;2:151-156.
37. McColl G, Koshaka H, Wicks I. High-dose chemotherapy and syngeneic hemopoietic stem cell transplantation for severe seronegative rheumatoid arthritis. Ann Intern Med. 1999;131:550-3.
38. McKendry RJ, Huebsch L and Leclair B. Progression of rheumatoid arthritis following bone marrow transplantation: a case report with a 13 year follow-up. Arthritis Rheum. 1996;39:1246-53.
40. Mondria T, Lamers CH, te Bockhorst PA, et al. Bone marrow transplantation fails to halt intrathecal lymphocyte actrivation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2008;79:1013-1015. doi: 10.1136/jnnp.2007.133520.
42. Muraro P, Douek DC. Renewing the T-cell repertoire to arrest autoimmune aggression. Trends Immunol. 2006;27:61-67. doi: 10.1016/j.it.2005.12.003.
47. Saccardi R and Gualandi F. Hematopoietic stem cell transplantation procedures. Autoimmunity. 2008;41:570-576. doi: 10.1080/08916930802197776.
48. Saccardi R, Di Gioia M and Bosi A. Haematopoietic stem cell transplantation for autoimmune disorders. Current Opinion Hematol. 2008;594-600.
49. Shevchenko YL, Novik AA, Kuznetsov AN, et al. High dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Exp Hematol. 2008;36:922-928. doi: 10.1016/j.exphem.2008.03.001.
52. Sun W, Popat V, Hutton G, et al. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell graft in multiple sclerosis. Brain. 2004;127:996-1008.
56. Uccelli A, Mancardi GL and Chiesa S. Is there a role for mesenchymal stem cells in autoimmune diseases? Autoimmunity. 2008;41:392-395. doi:10.1080/08916930802200166.
57. Urban C, Lackner H, Sovinz P, et al. Succesful unrelated cord blood transplantation in a 7- year old boy with Evans syndrome refractory to immunosuppression and double autologous stem cell transplantation. Eur J Haematol. 2006;76:326-330. doi: 10.1111/j.0902-4441.2006.t01-1-EJH2549.x.
58. van Bekkum DW. Stem cell transplantation for autoimmune disorders. Preclinical experiments. Best Practice & Research Clin Haematol. 2004;17:201-222. doi:10.1016/j.beha.2004.04.003.
59. van Oosterhout M, Verburg RJ, Levahrt EW, et al. High dose chemotherapy and syngeneic stem cell transplantation in a patient with refractory rheumatoid arthritis: poor response associated with persistence of host antibodies and synovial abnormalities. Ann Rheum Dis. 2005;64:1783-5. doi: 10.1136/ard.2004.034793.
60. van Wijmeersch B, Spranger B, Rutgeers O, et al. Allogeneic bone marrow transplantation in models of experimental autoimmune encephalomyelitis: evidence for a Graft-versus-Autoimmunity effect. Biol Blood Marrow Transplant. 2007;13:627-637. doi: 10.1016/j.bbmt.2007.03.001.
61. Voltarelli JC, Couri CE, Stracieri AB, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type I diabetes mellitus. JAMA. 2007;297:1568-1576. doi:10.1001/jama.297.14.1568.
62. Young N, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108:2509-2518. 10.1182/blood-2006-03-010777.
63. Zhang L, Bertucci AM, Ramsey-Goldman R, Burt RK, et al. Regulatory T cell (treg) subset return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remisison of lupus. J Immunol. 2009;183:6346-6358. doi: 10.4049/jimmunol.0901773.
Альберто М. Мармонт
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18274" ["VALUE"]=> array(2) { ["TEXT"]=> string(2787) "<p class="bodytext">Для обоснования целесообразности трансплантации гемопоэтических стволовых клеток (ТГСК) при тяжёлых аутоиммунных болезнях (ТАБ) приводятся результаты двух различных серий исследований. Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования. </p> <h3>Ключевые слова</h3> <p>аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2741) "Для обоснования целесообразности трансплантации гемопоэтических стволовых клеток (ТГСК) при тяжёлых аутоиммунных болезнях (ТАБ) приводятся результаты двух различных серий исследований. Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования.
Ключевые слова
аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация
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" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18282" ["VALUE"]=> array(2) { ["TEXT"]=> string(1109) "<p class="bodytext">Two different sets of investigation are at the origin of hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The experimental evidence consisted in the transfer/cure of animal SADs as murine lupus by means of allogeneic but also, almost paradoxically, autologous HSCT. The clinical arm comes from serendipitous reports of patients allotransplanted for coincidental diseases, and ultimately cured of both conditions. Important multicentric prospective trials are ongoing to compare ASCT to the best available non-transplant therapies, but it may be argued that in the end both approaches will be integrated for single patients, and that new agents will possibly alter present strategies. Allogeneic STC is eliciting great expectations, but the burden of higher mortality and morbidity as a result of GVHD in the first place must be considered, even when making recourse to reduced conditioning regimens (RIC). </p> <h3>Keywords</h3> <p>autoimmune diseases, hematopoietic stem cell transplantation </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1063) "Two different sets of investigation are at the origin of hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The experimental evidence consisted in the transfer/cure of animal SADs as murine lupus by means of allogeneic but also, almost paradoxically, autologous HSCT. The clinical arm comes from serendipitous reports of patients allotransplanted for coincidental diseases, and ultimately cured of both conditions. Important multicentric prospective trials are ongoing to compare ASCT to the best available non-transplant therapies, but it may be argued that in the end both approaches will be integrated for single patients, and that new agents will possibly alter present strategies. Allogeneic STC is eliciting great expectations, but the burden of higher mortality and morbidity as a result of GVHD in the first place must be considered, even when making recourse to reduced conditioning regimens (RIC).
Keywords
autoimmune diseases, hematopoietic stem cell transplantation
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autoimmune diseases, hematopoietic stem cell transplantation
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Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования. </p> <h3>Ключевые слова</h3> <p>аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2741) "Для обоснования целесообразности трансплантации гемопоэтических стволовых клеток (ТГСК) при тяжёлых аутоиммунных болезнях (ТАБ) приводятся результаты двух различных серий исследований. Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования.
Ключевые слова
аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(2741) "Для обоснования целесообразности трансплантации гемопоэтических стволовых клеток (ТГСК) при тяжёлых аутоиммунных болезнях (ТАБ) приводятся результаты двух различных серий исследований. Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования.
Ключевые слова
аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация
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High-dose immunosuppressive therapy with hemopoietic stem cell transplantation (HSCT) was already introduced into the management of multiple sclerosis (MS) in 1995 [8]. The method was based on the concept of an immunological “renewal” after (near)-complete eradication of the aberrant immune system responsible for the development of the disease. Experimental hemopoietic transplants in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), performed in Israel and in the Netherlands, showed that the induction of profound and long-lasting immunosuppression followed by allogeneic or syngeneic or (pseudo)-autologous HSCT can actually have a beneficial impact on the course of EAE [3]. At that time, there was a need for new effective treatments for MS; in particular for the rapidly progressing, therapy-resistant cases, as the results of the existing standard therapies, namely interferon-beta and glatiramer acetate, were rather moderate to poor and their effect on the progression of disability was only marginal.
In order to eradicate the immune system and in view of the lack of a purely immunotoxic regimen, the proposal was for MS patients to be treated with high-dose chemotherapeutic agents (carmustin/ etoposide/ araC/ melphalan or busulfan/ cyclophosphamide) or total body irradiation (TBI), in the way patients with lymphoma or leukemia are conditioned for HSCT. To rescue the patient, autologous grafts were used, purged of T cells or CD34+ cell-selected. These were harvested from peripheral blood stem cells mobilized by cyclophosphamide plus G-CSF prior to HSCT. Intravenous anti-lymphocyte globulins (ALG, ATG) were also administered in the peri-transplant period in order to further eradicate any auto-reactive lymphocytes surviving the conditioning regimen or re-infused with the autologous graft. The “debulking” of autoreactive clones followed by reconstitution of the immune system in the presence of auto-antigens was speculated to bring about, apart from the abrogation of inflammation, qualitative changes as well, which might induce a degree of self-tolerance.
Since 1995, a number of centers in the European Union, Russia, Israel, China, USA, Canada, and Latin America have reported their experience in treating progressing, mainly advanced-stage and standard-therapy-resistant MS with high-dose immunosuppression and HSCT [9]. It is estimated that more than 400 patients have so far been treated worldwide, and favorable results have been reported with certain spectacular and long-lasting beneficial outcomes. However, after fourteen years of experience, the number of centers performing HSCT for MS still remains limited and few patients are referred for this kind treatment, which has not yet been accepted as an established therapy for aggressive MS because the neurological communities have constantly kept a skeptical attitude towards it. The reason lies mainly in the toxic complications of HSCT, especially in the risk of mortality associated with the procedure, which may be elevated in improperly selected patients [25]. This attitude has, unfortunately, prevented the accomplishment of comparative studies that were initiated in Europe (ASTIMS) and the USA (MIST, HALTMS) [11] some years ago and have not yet been finalized. In the meantime, other therapies emerged that were claimed to give good results in MS, e.g., mitoxantrone, alemtuzumab, rituximab, and natalizumab.
HSCT has been shown to be a most powerful immunosuppressive and anti-inflammatory treatment. Since 2000, all communications have consistently reported a dramatic, almost 100%, reduction in, or disappearance of, disease activity (inflammation) on magnetic resonance imaging (MRI) which is retained with time and has not been observed as an outcome of any other MS treatment [16, 26, 10, 23]. Also, brain atrophy, which seems to continue after HSCT as a result of edema resolution, slows down after the 2nd post-HSCT year [22, 12]. Consequently, patients with a lot of inflammation in the CNS experience substantial improvement of their disability status. On the other hand, patients with long-standing disease and those with primary progressive MS, i.e., cases in which the neurodegenerative component of the disease prevails, may not respond to HSCT [4]. This has been detected clinically and also in histopathological examinations of autopsy material, which show ongoing demyelination and axonal damage despite marked suppression of inflammation [19].
With regard to the clinical results of HSCT, it must first be noted that the great majority of the patient series treated worldwide had advanced disease with median EDSS scores of 6 to 6.5, while about 20% of the patients had primary progressive MS. All patients had evidence of disease progression over the twelve months preceding HSCT and/or gadolinium-enhancing lesions in MRI. After HSCT, improvement of disability scores by 1 to 4 steps was observed with a great reduction in the yearly relapse rate and a probability of disease progression-free survival (PFS) of 60–80% at three years [9, 25, 11, 10, 18]. At 10 years post-HSCT, PFS was around 65% for secondary and 40% for primary progressive MS (Fassas, unpublished data). Moreover, the patients’ quality of life and the physical and mental health have also been reported to improve [24]. The most dramatic effect, however, was seen in the so-called “malignant” cases of MS, which have a devastating course unresponsive to any standard therapy. In such cases, HSCT has been shown to be life-saving, with meaningful clinical improvement and long-standing disease stabilization [17, 14, 21, 15, 7].
From the immunological point of view, the effects of HSCT, especially the long-term ones on disease stabilization or on reduction in activity, do not seem to derive only from the immunosuppressive effect of the conditioning regimen, i.e., the “debulking” of auto-reactive clones, because MBP-recognizing T cells usually reappear within a year after HSCT [27, 6]. Immunological studies have shown that the speculated immunological remodulation can actually become a fact after HSCT. Expansion of naive CD4+ cells of thymic origin, decrease of memory T cells, reconstitution of broad clonal diversity, and renewal of clonal specificities have been described to occur after HSCT using high-intensity conditioning regimens (e.g. busulfan 16mg/kg.b.wt. or TBI) [20]. These changes may possibly create tolerance or tip the immunological balance towards suppression of autoimmunity and explain the long-standing beneficial effects of HSCT. Recently, there has been a tendency to use “light” conditioning regimens, e.g., cyclophosphamide 200mg/k.b.wt. plus alemtuzumab or ATG in order to diminish the procedure-related mortality risk. Low-intensity conditioning regimens are, too, capable of inducing immune changes, like the renewal of the balance between CD4+25+FoxP3 regulatory and other T cells or like the deviation of a proinflammatory phenotype of autoimmune cells to a tolerant one [2, 1]. There seems to be a difference in the kind of immune reconstitution brought about by the two types of conditioning, high and low, and we still do not know whether this difference might have the same or a different (better or worse) impact on the clinical outcome. It has been reported, however, that, although “light” conditioning regimens do have less toxicity, they are also associated with more autoimmune relapse after HSCT, compared to “strong” regimens [5, 13]. The regimen of cyclophosphamide plus ATG is less toxic than others but does not appear to have the same good impact on MRI compared to the intermediate-intensity BEAM (carmustine/ etoposide/ araC/ melphalan) [18]. The number of relapses after HSCT with cyclophosphamide plus alemtuzumab or ATG appears somewhat elevated [5], and it is still too early to conclude on the long-term effects on disease progression.
HSCT is a toxic treatment with a variety of complications depending on the intensity of the conditioning regimen [9, 25]. Although a patient may undergo HSCT without any problems, it not unusual for infections, organ damage, and transient neurological worsening to develop during the early post-transplant period. Secondary autoimmune phenomena may also appear late after HSCT. In the two EBMT reports of 2002 and 2006, the procedure-related mortality was 6% in 85 cases [9] and 5.3% in 185 cases [25], respectively. However, the mortality has dropped considerably from 7.3% in transplants before the year 2000 to 1.3% after the year 2000 [18]. This is the result of better patient selection, reserving HSCT for younger, ambulatory, not too-disabled patients, and avoiding the use of too “strong” and too intensive conditioning regimens, i.e., ex-vivo plus in-vivo, and lymphocyte depletion.
In summary, the analyses of the EBMT registry cases have shown that HSCT is active in the inflammatory phases of MS and is capable of slowing down the progression of the disease in relapsing/remitting cases and in patients that have recently entered the secondary progressive phase. Younger patients with low disability scores are more likely to benefit from this therapy. HSCT can be life-saving in desperate cases of very aggressive, rapidly progressing disease, which is refractory to any other therapy. HSCT is not curative, but it may offer prolonged periods of clinical disease stabilization or may change an aggressive disease course. It is not a therapy for the general population of MS patients, as the benefit does not justify the morbidity and mortality risks in cases of already stable disease, in primary progressive or long-standing secondary progressive MS, in cases without gadolinium-positive (inflammatory) lesions on MRI, and in wheelchair-bound patients (EDSS score ≥7) with low performance status and medical co-morbidities. In contrast, the best candidates, in whom the benefit of HSCT outweighs the risks, are young (below 40 years of age), who are still ambulatory, have active and rapidly progressing disease with inflammatory lesions in the CNS, and are in relapsing/remitting or recent secondary progressive phase without much disability. If such MS patients have no accompanying medical co-morbidities precluding transplantation, they may undergo HSCT with a practically zero mortality risk and a good outlook for clinical improvement and/or long disease stability.
It is well known that MS is a very difficult disease in which to show the efficacy of a therapy. Despite the very interesting outcomes of HSCT in treatment of MS, it is only in comparative trials that its superiority over other therapies can be demonstrated. Therefore, it is absolutely necessary to complete the running randomized studies comparing HSCT with mitoxantrone (ASTIMS) or other standard therapies. Unless such trials yield their final results, HSCT will never be approved as an established therapy for MS patients, who may therefore miss the opportunity of receiving an active, powerful immunosuppressive and immunomodulating treatment having a long-term beneficial impact on the course of the disease.
References
1. Abrahamsson SV, et al. Effects of immunosupressive conditioning regimens on immune reconstitution after haematopoietic stem cell transplantation in patients with MS. Mult Scler. 2007;P814.
2. Abrahamsson S. and Muraro PA. Immune re-education following autologous hematopoietic stem cell transplantation. Autoimmunity. 2008;41:577-584.
3. van Bekkum DW. Stem cell transplantation for autoimmuine disorders. Preclinical experiments. Best Pract Res Clin Haematol. 2004;17:201-222.
5. Burt RK, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8:244-253.
6. Dubinsky AN, et al. T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant. 2009 June 22 [Epub ahead of print].
7. Fagius J, et al. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler. 2009;15:229-237.
9. Fassas A, et al. for the Autoimmune Disease Working Party of the EBMT (European Group for Blood and Marrow Transplantation): Hematopoietic stem cell transplantation for multiple sclerosis: a retrospective multicenter study. J Neurol. 2002;249:1088-1097.
10. Fassas A. and Nash R. Stem cell transplantation for autoimmune disorders. Multiple sclerosis. Best Pract Res Clin Haematol. 2004;17:247-262.
11. Fassas A. and Mancardi GL. Autologous hemopoietic stem cell transplantation for multiple sclerosis: is it worthwile? Autoimmunity. 2008;41:601-610.
13. Hamerschlak N, et al. Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplant. 2009 Jul6. [Epub ahead of print].
14. Havrdova E. Aggressive multiple sclerosis - is there a role for stem cell transplantation? J Neurol. 2005;252[Suppl 3]:III/34-III37.
15. Kimiskidis V, et al. Treatment of a malignant form of multiple sclerosis with immune ablation and autologous stem cell transplantation. Mult Scler. 2008;14:278-283.
16. Mancardi GL, et al. and the Italian GITMO-NEURO Intergroup on Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology. 2001;57:62-68.
17. Mancardi GL, et al. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler. 2005;11:367-371.
18. Mancardi G. and Saccardi R. Autologous haematopoetic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008;7:626-636.
21. Portaccio E, et al. Autologous hematopoietic stem cell transplantation for very active relapsing-remitting multiple sclerosis: report of two cases. Mult Scler. 2007;13:676-678.
23. Roccatagliata L, et al. Italian GITMO-NEURO Intergroup on Autologous Stem Cell Transplantation. The long-term effect of AHSCT on MRI measures of MS evolution: a five-year follow-up study. Mult Scler. 2007;13:1068-1070.
25. Saccardi R, et al. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
26. Saiz A, et al. Clinical and MRI outcome after autologous hemtopoietic stem cell transplantation in MS. Neurology. 2004;62:282-284.
27. Sun W, et al. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain. 2004;127:996-1008.
On the evolution of high-dose immunosuppressive therapy with autologous stem cell transplantation in multiple sclerosis
High-dose immunosuppressive therapy with hemopoietic stem cell transplantation (HSCT) was already introduced into the management of multiple sclerosis (MS) in 1995 [8]. The method was based on the concept of an immunological “renewal” after (near)-complete eradication of the aberrant immune system responsible for the development of the disease. Experimental hemopoietic transplants in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), performed in Israel and in the Netherlands, showed that the induction of profound and long-lasting immunosuppression followed by allogeneic or syngeneic or (pseudo)-autologous HSCT can actually have a beneficial impact on the course of EAE [3]. At that time, there was a need for new effective treatments for MS; in particular for the rapidly progressing, therapy-resistant cases, as the results of the existing standard therapies, namely interferon-beta and glatiramer acetate, were rather moderate to poor and their effect on the progression of disability was only marginal.
In order to eradicate the immune system and in view of the lack of a purely immunotoxic regimen, the proposal was for MS patients to be treated with high-dose chemotherapeutic agents (carmustin/ etoposide/ araC/ melphalan or busulfan/ cyclophosphamide) or total body irradiation (TBI), in the way patients with lymphoma or leukemia are conditioned for HSCT. To rescue the patient, autologous grafts were used, purged of T cells or CD34+ cell-selected. These were harvested from peripheral blood stem cells mobilized by cyclophosphamide plus G-CSF prior to HSCT. Intravenous anti-lymphocyte globulins (ALG, ATG) were also administered in the peri-transplant period in order to further eradicate any auto-reactive lymphocytes surviving the conditioning regimen or re-infused with the autologous graft. The “debulking” of autoreactive clones followed by reconstitution of the immune system in the presence of auto-antigens was speculated to bring about, apart from the abrogation of inflammation, qualitative changes as well, which might induce a degree of self-tolerance.
Since 1995, a number of centers in the European Union, Russia, Israel, China, USA, Canada, and Latin America have reported their experience in treating progressing, mainly advanced-stage and standard-therapy-resistant MS with high-dose immunosuppression and HSCT [9]. It is estimated that more than 400 patients have so far been treated worldwide, and favorable results have been reported with certain spectacular and long-lasting beneficial outcomes. However, after fourteen years of experience, the number of centers performing HSCT for MS still remains limited and few patients are referred for this kind treatment, which has not yet been accepted as an established therapy for aggressive MS because the neurological communities have constantly kept a skeptical attitude towards it. The reason lies mainly in the toxic complications of HSCT, especially in the risk of mortality associated with the procedure, which may be elevated in improperly selected patients [25]. This attitude has, unfortunately, prevented the accomplishment of comparative studies that were initiated in Europe (ASTIMS) and the USA (MIST, HALTMS) [11] some years ago and have not yet been finalized. In the meantime, other therapies emerged that were claimed to give good results in MS, e.g., mitoxantrone, alemtuzumab, rituximab, and natalizumab.
HSCT has been shown to be a most powerful immunosuppressive and anti-inflammatory treatment. Since 2000, all communications have consistently reported a dramatic, almost 100%, reduction in, or disappearance of, disease activity (inflammation) on magnetic resonance imaging (MRI) which is retained with time and has not been observed as an outcome of any other MS treatment [16, 26, 10, 23]. Also, brain atrophy, which seems to continue after HSCT as a result of edema resolution, slows down after the 2nd post-HSCT year [22, 12]. Consequently, patients with a lot of inflammation in the CNS experience substantial improvement of their disability status. On the other hand, patients with long-standing disease and those with primary progressive MS, i.e., cases in which the neurodegenerative component of the disease prevails, may not respond to HSCT [4]. This has been detected clinically and also in histopathological examinations of autopsy material, which show ongoing demyelination and axonal damage despite marked suppression of inflammation [19].
With regard to the clinical results of HSCT, it must first be noted that the great majority of the patient series treated worldwide had advanced disease with median EDSS scores of 6 to 6.5, while about 20% of the patients had primary progressive MS. All patients had evidence of disease progression over the twelve months preceding HSCT and/or gadolinium-enhancing lesions in MRI. After HSCT, improvement of disability scores by 1 to 4 steps was observed with a great reduction in the yearly relapse rate and a probability of disease progression-free survival (PFS) of 60–80% at three years [9, 25, 11, 10, 18]. At 10 years post-HSCT, PFS was around 65% for secondary and 40% for primary progressive MS (Fassas, unpublished data). Moreover, the patients’ quality of life and the physical and mental health have also been reported to improve [24]. The most dramatic effect, however, was seen in the so-called “malignant” cases of MS, which have a devastating course unresponsive to any standard therapy. In such cases, HSCT has been shown to be life-saving, with meaningful clinical improvement and long-standing disease stabilization [17, 14, 21, 15, 7].
From the immunological point of view, the effects of HSCT, especially the long-term ones on disease stabilization or on reduction in activity, do not seem to derive only from the immunosuppressive effect of the conditioning regimen, i.e., the “debulking” of auto-reactive clones, because MBP-recognizing T cells usually reappear within a year after HSCT [27, 6]. Immunological studies have shown that the speculated immunological remodulation can actually become a fact after HSCT. Expansion of naive CD4+ cells of thymic origin, decrease of memory T cells, reconstitution of broad clonal diversity, and renewal of clonal specificities have been described to occur after HSCT using high-intensity conditioning regimens (e.g. busulfan 16mg/kg.b.wt. or TBI) [20]. These changes may possibly create tolerance or tip the immunological balance towards suppression of autoimmunity and explain the long-standing beneficial effects of HSCT. Recently, there has been a tendency to use “light” conditioning regimens, e.g., cyclophosphamide 200mg/k.b.wt. plus alemtuzumab or ATG in order to diminish the procedure-related mortality risk. Low-intensity conditioning regimens are, too, capable of inducing immune changes, like the renewal of the balance between CD4+25+FoxP3 regulatory and other T cells or like the deviation of a proinflammatory phenotype of autoimmune cells to a tolerant one [2, 1]. There seems to be a difference in the kind of immune reconstitution brought about by the two types of conditioning, high and low, and we still do not know whether this difference might have the same or a different (better or worse) impact on the clinical outcome. It has been reported, however, that, although “light” conditioning regimens do have less toxicity, they are also associated with more autoimmune relapse after HSCT, compared to “strong” regimens [5, 13]. The regimen of cyclophosphamide plus ATG is less toxic than others but does not appear to have the same good impact on MRI compared to the intermediate-intensity BEAM (carmustine/ etoposide/ araC/ melphalan) [18]. The number of relapses after HSCT with cyclophosphamide plus alemtuzumab or ATG appears somewhat elevated [5], and it is still too early to conclude on the long-term effects on disease progression.
HSCT is a toxic treatment with a variety of complications depending on the intensity of the conditioning regimen [9, 25]. Although a patient may undergo HSCT without any problems, it not unusual for infections, organ damage, and transient neurological worsening to develop during the early post-transplant period. Secondary autoimmune phenomena may also appear late after HSCT. In the two EBMT reports of 2002 and 2006, the procedure-related mortality was 6% in 85 cases [9] and 5.3% in 185 cases [25], respectively. However, the mortality has dropped considerably from 7.3% in transplants before the year 2000 to 1.3% after the year 2000 [18]. This is the result of better patient selection, reserving HSCT for younger, ambulatory, not too-disabled patients, and avoiding the use of too “strong” and too intensive conditioning regimens, i.e., ex-vivo plus in-vivo, and lymphocyte depletion.
In summary, the analyses of the EBMT registry cases have shown that HSCT is active in the inflammatory phases of MS and is capable of slowing down the progression of the disease in relapsing/remitting cases and in patients that have recently entered the secondary progressive phase. Younger patients with low disability scores are more likely to benefit from this therapy. HSCT can be life-saving in desperate cases of very aggressive, rapidly progressing disease, which is refractory to any other therapy. HSCT is not curative, but it may offer prolonged periods of clinical disease stabilization or may change an aggressive disease course. It is not a therapy for the general population of MS patients, as the benefit does not justify the morbidity and mortality risks in cases of already stable disease, in primary progressive or long-standing secondary progressive MS, in cases without gadolinium-positive (inflammatory) lesions on MRI, and in wheelchair-bound patients (EDSS score ≥7) with low performance status and medical co-morbidities. In contrast, the best candidates, in whom the benefit of HSCT outweighs the risks, are young (below 40 years of age), who are still ambulatory, have active and rapidly progressing disease with inflammatory lesions in the CNS, and are in relapsing/remitting or recent secondary progressive phase without much disability. If such MS patients have no accompanying medical co-morbidities precluding transplantation, they may undergo HSCT with a practically zero mortality risk and a good outlook for clinical improvement and/or long disease stability.
It is well known that MS is a very difficult disease in which to show the efficacy of a therapy. Despite the very interesting outcomes of HSCT in treatment of MS, it is only in comparative trials that its superiority over other therapies can be demonstrated. Therefore, it is absolutely necessary to complete the running randomized studies comparing HSCT with mitoxantrone (ASTIMS) or other standard therapies. Unless such trials yield their final results, HSCT will never be approved as an established therapy for MS patients, who may therefore miss the opportunity of receiving an active, powerful immunosuppressive and immunomodulating treatment having a long-term beneficial impact on the course of the disease.
References
1. Abrahamsson SV, et al. Effects of immunosupressive conditioning regimens on immune reconstitution after haematopoietic stem cell transplantation in patients with MS. Mult Scler. 2007;P814.
2. Abrahamsson S. and Muraro PA. Immune re-education following autologous hematopoietic stem cell transplantation. Autoimmunity. 2008;41:577-584.
3. van Bekkum DW. Stem cell transplantation for autoimmuine disorders. Preclinical experiments. Best Pract Res Clin Haematol. 2004;17:201-222.
5. Burt RK, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8:244-253.
6. Dubinsky AN, et al. T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant. 2009 June 22 [Epub ahead of print].
7. Fagius J, et al. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler. 2009;15:229-237.
9. Fassas A, et al. for the Autoimmune Disease Working Party of the EBMT (European Group for Blood and Marrow Transplantation): Hematopoietic stem cell transplantation for multiple sclerosis: a retrospective multicenter study. J Neurol. 2002;249:1088-1097.
10. Fassas A. and Nash R. Stem cell transplantation for autoimmune disorders. Multiple sclerosis. Best Pract Res Clin Haematol. 2004;17:247-262.
11. Fassas A. and Mancardi GL. Autologous hemopoietic stem cell transplantation for multiple sclerosis: is it worthwile? Autoimmunity. 2008;41:601-610.
13. Hamerschlak N, et al. Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplant. 2009 Jul6. [Epub ahead of print].
14. Havrdova E. Aggressive multiple sclerosis - is there a role for stem cell transplantation? J Neurol. 2005;252[Suppl 3]:III/34-III37.
15. Kimiskidis V, et al. Treatment of a malignant form of multiple sclerosis with immune ablation and autologous stem cell transplantation. Mult Scler. 2008;14:278-283.
16. Mancardi GL, et al. and the Italian GITMO-NEURO Intergroup on Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology. 2001;57:62-68.
17. Mancardi GL, et al. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler. 2005;11:367-371.
18. Mancardi G. and Saccardi R. Autologous haematopoetic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008;7:626-636.
21. Portaccio E, et al. Autologous hematopoietic stem cell transplantation for very active relapsing-remitting multiple sclerosis: report of two cases. Mult Scler. 2007;13:676-678.
23. Roccatagliata L, et al. Italian GITMO-NEURO Intergroup on Autologous Stem Cell Transplantation. The long-term effect of AHSCT on MRI measures of MS evolution: a five-year follow-up study. Mult Scler. 2007;13:1068-1070.
25. Saccardi R, et al. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
26. Saiz A, et al. Clinical and MRI outcome after autologous hemtopoietic stem cell transplantation in MS. Neurology. 2004;62:282-284.
27. Sun W, et al. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain. 2004;127:996-1008.
Атанасиос Фассас
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Во всех сообщениях, начиная с 2000 г., отмечается существенное (почти на 100%) снижение, или полное исчезновение признаков заболевания (воспаления), выявляемое с помощью метода ядерно-магнитного резонанса, и этот эффект сохраняется в течение длительного времени, в отличие от всех других методов лечения РС. Несмотря на весьма впечатляющие результаты применения HSCT для лечения РС, её преимущества были продемонстрированы только в сравнительных исследованиях. Поэтому представляется абсолютно необходимым завершить текущие рандомизированные исследования по сравнению HSCT с митоксантроном (ASTIMS) или с другими стандартными методами терапии. Пока не будут получены окончательные результаты этих исследований, HSCT не может быть принят как общепризнанный метод лечения больных с РС, которые могут быть лишены возможности получить действительно эффективную иммуносупрессивную и иммуномодулирующую терапию с длительным положительным воздействием на течение болезни.
Athanasios Fassas
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["VALUE"]=> array(2) { ["TEXT"]=> string(2394) "<p class="bodytext">Высокодозная иммуносупрессивная терапия и трансплантация аутологичных гемопоэтических стволовых клеток (HSCT) была введена в практику лечения больных рассеянным склерозом (РС) в 1995 г. Было показано, что HSCT является здесь наиболее эффективной иммуносупрессивной и противовоспалительной терапией. <br /><br />Во всех сообщениях, начиная с 2000 г., отмечается существенное (почти на 100%) снижение, или полное исчезновение признаков заболевания (воспаления), выявляемое с помощью метода ядерно-магнитного резонанса, и этот эффект сохраняется в течение длительного времени, в отличие от всех других методов лечения РС. Несмотря на весьма впечатляющие результаты применения HSCT для лечения РС, её преимущества были продемонстрированы только в сравнительных исследованиях. Поэтому представляется абсолютно необходимым завершить текущие рандомизированные исследования по сравнению HSCT с митоксантроном (ASTIMS) или с другими стандартными методами терапии. Пока не будут получены окончательные результаты этих исследований, HSCT не может быть принят как общепризнанный метод лечения больных с РС, которые могут быть лишены возможности получить действительно эффективную иммуносупрессивную и иммуномодулирующую терапию с длительным положительным воздействием на течение болезни. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2360) "Высокодозная иммуносупрессивная терапия и трансплантация аутологичных гемопоэтических стволовых клеток (HSCT) была введена в практику лечения больных рассеянным склерозом (РС) в 1995 г. Было показано, что HSCT является здесь наиболее эффективной иммуносупрессивной и противовоспалительной терапией.
Во всех сообщениях, начиная с 2000 г., отмечается существенное (почти на 100%) снижение, или полное исчезновение признаков заболевания (воспаления), выявляемое с помощью метода ядерно-магнитного резонанса, и этот эффект сохраняется в течение длительного времени, в отличие от всех других методов лечения РС. Несмотря на весьма впечатляющие результаты применения HSCT для лечения РС, её преимущества были продемонстрированы только в сравнительных исследованиях. Поэтому представляется абсолютно необходимым завершить текущие рандомизированные исследования по сравнению HSCT с митоксантроном (ASTIMS) или с другими стандартными методами терапии. Пока не будут получены окончательные результаты этих исследований, HSCT не может быть принят как общепризнанный метод лечения больных с РС, которые могут быть лишены возможности получить действительно эффективную иммуносупрессивную и иммуномодулирующую терапию с длительным положительным воздействием на течение болезни.
Высокодозная иммуносупрессивная терапия и трансплантация аутологичных гемопоэтических стволовых клеток (HSCT) была введена в практику лечения больных рассеянным склерозом (РС) в 1995 г. Было показано, что HSCT является здесь наиболее эффективной иммуносупрессивной и противовоспалительной терапией.
Во всех сообщениях, начиная с 2000 г., отмечается существенное (почти на 100%) снижение, или полное исчезновение признаков заболевания (воспаления), выявляемое с помощью метода ядерно-магнитного резонанса, и этот эффект сохраняется в течение длительного времени, в отличие от всех других методов лечения РС. Несмотря на весьма впечатляющие результаты применения HSCT для лечения РС, её преимущества были продемонстрированы только в сравнительных исследованиях. Поэтому представляется абсолютно необходимым завершить текущие рандомизированные исследования по сравнению HSCT с митоксантроном (ASTIMS) или с другими стандартными методами терапии. Пока не будут получены окончательные результаты этих исследований, HSCT не может быть принят как общепризнанный метод лечения больных с РС, которые могут быть лишены возможности получить действительно эффективную иммуносупрессивную и иммуномодулирующую терапию с длительным положительным воздействием на течение болезни.
Autologous versus allogeneic hematopoietic stem cell transplantation
Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have some common and some clearly distinct goals. Both permit the application of high dose chemo-radiotherapy up to the dose limiting extramedullary toxicity; allogeneic HSCT in addition can replace a diseased host hematopoiesis, including the immune system, with a healthy donor hemopoiesis. In the case of an autoimmune disease, the necessary goal to be achieved still remains a matter of debate. High dose immunoablation can reset ontogenesis of the immune system in animal models of experimental encephalomyelitis as well as in clinical HSCT for multiple sclerosis in humans. In view of its significantly lower transplant-related mortality, autologous HSCT currently remains the preferred choice in clinical studies.
Hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for many patients with severe congenital or acquired malignant or non-malignant disorders of the hematopoietic system, and for chemo-, radio-, or immuno-sensitive malignancies [1, 2]. Experimental animal studies, incidental reports from patients with HSCT for another indication but concomitant autoimmune disorders, and results from pilot studies have documented that complete remissions can be obtained in situations of severe treatment-refractory autoimmune disorders [3-6]. Animal data give clear indications that some forms of congenital autoimmune diseases can only be cured by allogeneic HSCT. Other forms of animal autoimmune diseases, considered as acquired immune disorders can just as clearly be cured by autologous HSCT alone [4, 5]. The situation is less clear in humans. Generally, autoimmune disorders in humans are considered to be induced by three independent components: a) inherited factors such as certain defined HLA-antigens, b) environmental factors such as smoking in rheumatoid arthritis and, c) chance phenomena [7].
These considerations make it clear that autologous HSCT cannot eradicate the congenital factor; it might, however, be sufficient to control the inflammatory component that was induced by chance through environmental factors in an individual patient. As such, the situation in autoimmune disorders is not so much different from the case of clonally aberrant lymphoid reactions in patients with lymphoid malignancies. In some of these high dose chemotherapy is sufficient for control of the disease; in others, an allogeneic healthy novel immune system might be required. These concepts were already well known more than ten years ago, when the European Group for Blood and Marrow Transplantation (EBMT) and the European League Against Rheumatism (EULAR) released a joint statement on the potential use of HSCT for treatment of patients with severe autoimmune disorders: the disease should be severe enough to justify the risk, the disease should not be so advanced not to permit clinical benefit for the patient, autologous HSCT should be the preferred choice, and standard techniques should be used [6, 9].
This view has not changed since. The experience from more than 200,000 HSCT procedures worldwide give some clear indications as to the potential benefits and risks of both allogeneic and autologous HSCT. Allogeneic HSCT is always linked with immunological complications, graft rejection (Host-versus-Graft reaction; HvG) and the reverse, rejection of the recipient by the immunocompetent transplanted immune system (Graft-versus-Host disease; GvHD). Furthermore, time to recovery of complete immuno-competence is considerably longer in allogeneic HSCT than in autologous HSCT. The reasons for this delayed immune recovery are probably manifold: donor-host interaction is required for competent immune response, and immunosuppression is needed to suppress both HvG reaction and GvHD. This combined and prolonged immuno-incompetence is associated with a prolonged higher risk for bacterial, fungal, viral, and parasitic infections in allogeneic, compared to autologous HSCT. For these reasons, allogeneic HSCT is associated with higher transplant related mortality (TRM) in the early as well as in the late post-transplantation period. As a benefit, allogeneic HSCT is devoid of malignant (in the case of HSCT for a malignant disease) or autoreactive (in the case of autoimmune disease) stem, precursor, or effector cells. The risk of relapse is significantly higher after autologous HSCT in all disease categories examined. The net balance of benefit and detrimental effects between autologous and allogeneic HSCT is not easy to assess. It can be very clear in some congenital or high-risk malignancies. In others, years may elapse until the beneficial effects of reduced relapse become higher than the early years of life lost after allogeneic HSCT. Overall, the best results are always obtained with syngeneic HSCT; if there is a syngeneic donor, HSCT is the preferred choice. This is true despite the fact that syngeneic twins possess an inherent risk of developing the same disease as their twin. This disease concordance for twins has clearly been shown in autoimmune disorders and in hematological malignancies [1, 10, 11].
The discordant effects of major histocompatibility antigens holds true as well for minor histocompatibility antigens (mHAg). This has been shown for the H-Y encoded mHAg. Male stem cells are more likely to be rejected by female recipients; female donors are more likely to induce more GvHD in male recipients. The detrimental effects of increased TRM in the female donor-male recipient situation never outweigh the benefits of a reduced relapse rate. Hence it is unlikely that beneficial allogeneic effects, whatever their mechanism, will outweigh the negative impact [12]. The situation in severe autoimmune disorders is even more complicated than after allogeneic HSCT for a malignancy. Some clinical features of chronic GvHD are indistinguishable from some autoimmune disorders [13]. Specifically, chronic GvHD was first described based on its resemblance with Sjögren’s syndrome, systemic sclerosis, or primary biliary cirrhosis [14]. Last but not least, late altered immunity has recently been described as a new late effect after allogeneic HSCT [15]. This syndrome includes some clinical and laboratory aspects of autoimmunity.
The introduction of reduced intensity conditioning transplants (RIC HSCT) has revolutionized clinical HSCT, expanded HSCT to patients with co-morbidities, and has abolished age limits [16]. It has also created big expectations that RIC HSCT might favor the clinical applicability of allogeneic HSCT for patients with severe autoimmune disorders. Indeed, RIC HSCT was recommended via a joint statement on allogeneic HSCT by an international panel [17]. However, experience over the last ten years with RIC HSCT for hematological malignancies does not support such expectations. Explanations are simple. The main reasons for death after an allogeneic HSCT are relapse, immunological complications (HvG and GvHD), infectious complications, and the toxicity of the conditioning regimen.
Conditioning regimens
The contribution to toxicity of the conditioning regimen is therefore just about one quarter of all toxicity. Earlier experience had clearly shown that increased conditioning intensity could reduce relapse risk, but only at the expense of higher TRM. The reverse is now the case. Reduced conditioning can reduce deaths from toxicity of the conditioning; it cannot reduce the risk of immunological complications. It does so at the expense of an increased relapse rate. The net benefit is in favor of the RIC HSCT early on, e.g., at day 100. It is lost at five-year follow up. RIC HSCT does not alter the inherent risk of the key pre-transplant patient factors as established by the EBMT risk score: age of the patient, disease stage, time interval from diagnosis to transplant, donor type, and donor recipient gender combination [11].
In summary, all current available information suggests that autologous HSCT should remain the standard approach to clinical HSCT for patients with severe autoimmune disorders including multiple sclerosis [18]. Syngeneic twin donors, if they exist, are preferred. Allogeneic HSCT can be discussed in rare patients with specific features that they are likely to benefit more, e.g., young patients with no co-morbidities and hematological autoimmune cytopenias [19].
References
1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;27:1813-26. pmid: 16641398.
2. Gratwohl A, Baldomero H, Aljurf M, et al. Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303:1617-24. pmid: 20424252.
5. Van Bekkum DW. Stem cell transplantation for autoimmune disorders. Preclinical experiments. Best Pract Res Clin Haematol. 2004;17:201-22. doi: 10.1016/j.beha.2004.04.003.
7. Davidson A, Diamond B. Autoimmune diseases. N Engl J Med. 2001;345:340-50. pmid: 11484692.
8. Ringdén O, Karlsson H, Olsson R, Omazic B, Uhlin M. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009;147:614-33. doi: 10.1111/j.1365-2141.2009.07886.x.
9. Marmont A, Tyndall A, Gratwohl A, Vischer T. Haemopoietic precursor-cell transplants for autoimmune diseases. Lancet. 1995;345:978.
10. Gratwohl A. Risk assessment in haematopoietic stem cell transplantation. Best Pract Res Clin Haematol. 2007;20:119-124. doi: 10.1016/j.beha.2006.10.011.
11. Gratwohl A, Stern M, Brand R et al. Risk score for outcome after alloge¬neic hematopoietic stem cell transplantation: a Retrospective Analysis. Cancer. 2009;115:4715-26. doi: 10.1002/cncr.24531.
13. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945-56.
14. Gratwohl AA, Moutsopoulos HM, Chused TM, Akizuki M, Wolf RO, Sweet JB, Deisseroth AB. Sjögren-type syndrome after allogeneic bone-marrow transplantation. Ann Intern Med. 1977;87:703-6. pmid: 22306.
16. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628-33. doi: 10.1016/j.bbmt.2009.07.004.
18. Farge D, Labopin M, Tyndall A, et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010;95:284-92.
19. Daikeler T, Hügle T, Farge D, et al. Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant. 2009;44:27-33. doi:10.1038/bmt.2008.424.
" ["~DETAIL_TEXT"]=> string(14158) "Autologous versus allogeneic hematopoietic stem cell transplantation
Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have some common and some clearly distinct goals. Both permit the application of high dose chemo-radiotherapy up to the dose limiting extramedullary toxicity; allogeneic HSCT in addition can replace a diseased host hematopoiesis, including the immune system, with a healthy donor hemopoiesis. In the case of an autoimmune disease, the necessary goal to be achieved still remains a matter of debate. High dose immunoablation can reset ontogenesis of the immune system in animal models of experimental encephalomyelitis as well as in clinical HSCT for multiple sclerosis in humans. In view of its significantly lower transplant-related mortality, autologous HSCT currently remains the preferred choice in clinical studies.
Hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for many patients with severe congenital or acquired malignant or non-malignant disorders of the hematopoietic system, and for chemo-, radio-, or immuno-sensitive malignancies [1, 2]. Experimental animal studies, incidental reports from patients with HSCT for another indication but concomitant autoimmune disorders, and results from pilot studies have documented that complete remissions can be obtained in situations of severe treatment-refractory autoimmune disorders [3-6]. Animal data give clear indications that some forms of congenital autoimmune diseases can only be cured by allogeneic HSCT. Other forms of animal autoimmune diseases, considered as acquired immune disorders can just as clearly be cured by autologous HSCT alone [4, 5]. The situation is less clear in humans. Generally, autoimmune disorders in humans are considered to be induced by three independent components: a) inherited factors such as certain defined HLA-antigens, b) environmental factors such as smoking in rheumatoid arthritis and, c) chance phenomena [7].
These considerations make it clear that autologous HSCT cannot eradicate the congenital factor; it might, however, be sufficient to control the inflammatory component that was induced by chance through environmental factors in an individual patient. As such, the situation in autoimmune disorders is not so much different from the case of clonally aberrant lymphoid reactions in patients with lymphoid malignancies. In some of these high dose chemotherapy is sufficient for control of the disease; in others, an allogeneic healthy novel immune system might be required. These concepts were already well known more than ten years ago, when the European Group for Blood and Marrow Transplantation (EBMT) and the European League Against Rheumatism (EULAR) released a joint statement on the potential use of HSCT for treatment of patients with severe autoimmune disorders: the disease should be severe enough to justify the risk, the disease should not be so advanced not to permit clinical benefit for the patient, autologous HSCT should be the preferred choice, and standard techniques should be used [6, 9].
This view has not changed since. The experience from more than 200,000 HSCT procedures worldwide give some clear indications as to the potential benefits and risks of both allogeneic and autologous HSCT. Allogeneic HSCT is always linked with immunological complications, graft rejection (Host-versus-Graft reaction; HvG) and the reverse, rejection of the recipient by the immunocompetent transplanted immune system (Graft-versus-Host disease; GvHD). Furthermore, time to recovery of complete immuno-competence is considerably longer in allogeneic HSCT than in autologous HSCT. The reasons for this delayed immune recovery are probably manifold: donor-host interaction is required for competent immune response, and immunosuppression is needed to suppress both HvG reaction and GvHD. This combined and prolonged immuno-incompetence is associated with a prolonged higher risk for bacterial, fungal, viral, and parasitic infections in allogeneic, compared to autologous HSCT. For these reasons, allogeneic HSCT is associated with higher transplant related mortality (TRM) in the early as well as in the late post-transplantation period. As a benefit, allogeneic HSCT is devoid of malignant (in the case of HSCT for a malignant disease) or autoreactive (in the case of autoimmune disease) stem, precursor, or effector cells. The risk of relapse is significantly higher after autologous HSCT in all disease categories examined. The net balance of benefit and detrimental effects between autologous and allogeneic HSCT is not easy to assess. It can be very clear in some congenital or high-risk malignancies. In others, years may elapse until the beneficial effects of reduced relapse become higher than the early years of life lost after allogeneic HSCT. Overall, the best results are always obtained with syngeneic HSCT; if there is a syngeneic donor, HSCT is the preferred choice. This is true despite the fact that syngeneic twins possess an inherent risk of developing the same disease as their twin. This disease concordance for twins has clearly been shown in autoimmune disorders and in hematological malignancies [1, 10, 11].
The discordant effects of major histocompatibility antigens holds true as well for minor histocompatibility antigens (mHAg). This has been shown for the H-Y encoded mHAg. Male stem cells are more likely to be rejected by female recipients; female donors are more likely to induce more GvHD in male recipients. The detrimental effects of increased TRM in the female donor-male recipient situation never outweigh the benefits of a reduced relapse rate. Hence it is unlikely that beneficial allogeneic effects, whatever their mechanism, will outweigh the negative impact [12]. The situation in severe autoimmune disorders is even more complicated than after allogeneic HSCT for a malignancy. Some clinical features of chronic GvHD are indistinguishable from some autoimmune disorders [13]. Specifically, chronic GvHD was first described based on its resemblance with Sjögren’s syndrome, systemic sclerosis, or primary biliary cirrhosis [14]. Last but not least, late altered immunity has recently been described as a new late effect after allogeneic HSCT [15]. This syndrome includes some clinical and laboratory aspects of autoimmunity.
The introduction of reduced intensity conditioning transplants (RIC HSCT) has revolutionized clinical HSCT, expanded HSCT to patients with co-morbidities, and has abolished age limits [16]. It has also created big expectations that RIC HSCT might favor the clinical applicability of allogeneic HSCT for patients with severe autoimmune disorders. Indeed, RIC HSCT was recommended via a joint statement on allogeneic HSCT by an international panel [17]. However, experience over the last ten years with RIC HSCT for hematological malignancies does not support such expectations. Explanations are simple. The main reasons for death after an allogeneic HSCT are relapse, immunological complications (HvG and GvHD), infectious complications, and the toxicity of the conditioning regimen.
Conditioning regimens
The contribution to toxicity of the conditioning regimen is therefore just about one quarter of all toxicity. Earlier experience had clearly shown that increased conditioning intensity could reduce relapse risk, but only at the expense of higher TRM. The reverse is now the case. Reduced conditioning can reduce deaths from toxicity of the conditioning; it cannot reduce the risk of immunological complications. It does so at the expense of an increased relapse rate. The net benefit is in favor of the RIC HSCT early on, e.g., at day 100. It is lost at five-year follow up. RIC HSCT does not alter the inherent risk of the key pre-transplant patient factors as established by the EBMT risk score: age of the patient, disease stage, time interval from diagnosis to transplant, donor type, and donor recipient gender combination [11].
In summary, all current available information suggests that autologous HSCT should remain the standard approach to clinical HSCT for patients with severe autoimmune disorders including multiple sclerosis [18]. Syngeneic twin donors, if they exist, are preferred. Allogeneic HSCT can be discussed in rare patients with specific features that they are likely to benefit more, e.g., young patients with no co-morbidities and hematological autoimmune cytopenias [19].
References
1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;27:1813-26. pmid: 16641398.
2. Gratwohl A, Baldomero H, Aljurf M, et al. Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303:1617-24. pmid: 20424252.
5. Van Bekkum DW. Stem cell transplantation for autoimmune disorders. Preclinical experiments. Best Pract Res Clin Haematol. 2004;17:201-22. doi: 10.1016/j.beha.2004.04.003.
7. Davidson A, Diamond B. Autoimmune diseases. N Engl J Med. 2001;345:340-50. pmid: 11484692.
8. Ringdén O, Karlsson H, Olsson R, Omazic B, Uhlin M. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009;147:614-33. doi: 10.1111/j.1365-2141.2009.07886.x.
9. Marmont A, Tyndall A, Gratwohl A, Vischer T. Haemopoietic precursor-cell transplants for autoimmune diseases. Lancet. 1995;345:978.
10. Gratwohl A. Risk assessment in haematopoietic stem cell transplantation. Best Pract Res Clin Haematol. 2007;20:119-124. doi: 10.1016/j.beha.2006.10.011.
11. Gratwohl A, Stern M, Brand R et al. Risk score for outcome after alloge¬neic hematopoietic stem cell transplantation: a Retrospective Analysis. Cancer. 2009;115:4715-26. doi: 10.1002/cncr.24531.
13. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945-56.
14. Gratwohl AA, Moutsopoulos HM, Chused TM, Akizuki M, Wolf RO, Sweet JB, Deisseroth AB. Sjögren-type syndrome after allogeneic bone-marrow transplantation. Ann Intern Med. 1977;87:703-6. pmid: 22306.
16. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628-33. doi: 10.1016/j.bbmt.2009.07.004.
18. Farge D, Labopin M, Tyndall A, et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010;95:284-92.
19. Daikeler T, Hügle T, Farge D, et al. Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant. 2009;44:27-33. doi:10.1038/bmt.2008.424.
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Вся имеющаяся в настоящее время информация предполагает, что аутологичные ТГСК должны оставаться стандартным подходом в клинической трансплантации для лечения больных с тяжелыми аутоиммунными заболеваниями, в том числе – при рассеянном склерозе. Выбор в пользу аллогенных ТГСК должен рассматриваться у немногих больных с особыми характеристиками, при которых, возможно, выгоднее использовать аллогенную ТГСК, например, для молодых пациентов без сопутствующих заболеваний и гематологических аутоиммунных цитопений. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1307) "Проведение аутологичных и аллогенных трансплантаций гемопоэтических стволовых клеток (ТГСК) имеет ряд общих целей, а также некоторые четкие различия по задачам их применения. Вся имеющаяся в настоящее время информация предполагает, что аутологичные ТГСК должны оставаться стандартным подходом в клинической трансплантации для лечения больных с тяжелыми аутоиммунными заболеваниями, в том числе – при рассеянном склерозе. Выбор в пользу аллогенных ТГСК должен рассматриваться у немногих больных с особыми характеристиками, при которых, возможно, выгоднее использовать аллогенную ТГСК, например, для молодых пациентов без сопутствующих заболеваний и гематологических аутоиммунных цитопений.
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High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) is a promising approach to treatment of multiple sclerosis (MS) patients, since there are no effective treatment methods for this disease [4-7, 10]. HDCT+ASCT has been performed in more than 700 MS patients since 1995 all over the world. However, the patient selection criteria for HDIT +ASCT are still unclear and the proper selection of patients for transplantation remains the key issue [3, 9, 11]. In Russia more than 180 transplantations in MS patients were done within 10 years within a prospective Phase II multicenter trial coordinated by the Russian Cooperative Group for Cellular Therapy. The follow-up results of the patients who were enrolled in the Military Medical Academy (St. Petersburg) and Pirogov National Medical Surgical Center (Moscow) since 1999 are reported here. We focused on the efficacy of HDIT +ASCT in patients with different types and stages of MS. The patients underwent early, conventional, or salvage/late transplantation in accordance with the concept of HDIT +ASCT in MS [12, 13]. There are 3 strategies of HDIT +ASCT (Table 1). Early ASCT (in MS patients with EDSS 1.5–3.0) is performed soon after diagnosis in the case of primary refractory disease or poor prognosis. Conventional ASCT (EDSS 3.5–6.5) is performed in patients with secondary refractory disease. Salvage ASCT (EDSS 7.0–8.0) is an option in the case of high disease activity and rapid neurological deterioration in late stages of the disease.
Patients and Methods
132 MS patients were included in this study with a mean age of 33.0, and a male/female split of 58/74. The distribution according to the disease type was as follows: secondary progressive (SPMS): 57 patients, primary progressive (PPMS): 23, progressive-relapsing (PRMS): 9 and relapsing-remitting (RRMS): 43.
Criteria for patient selection were: age between 18 and 55 years, diagnosis of multiple sclerosis verified by clinical and laboratory findings, EDSS score 1.5–8.0, normal mental status, and absence of severe concomitant diseases.
The disease activity was determined either by magnetic resonance imaging scans displaying active lesions in the CNS (i.e., gadolinium-enhancing lesions, new or enlarging lesions on serial scans) or by clinical assessment showing rapid neurological deterioration, e.g., 0.5-point increase on the EDSS during the 6 months preceding enrollment.
Table 1. Classification of HDIT +ASCT in MS patients
|
Type of transplantation |
Pathogenetic goal |
Overall goal |
Timing |
|---|---|---|---|
|
Early transplantation |
To prevent the irreversible damage of the CNS by immunopathological process |
To stop the disease progression and |
In early stages of the disease in cases of poor prognosis |
|
Conventional transplantation |
|
To prevent the exacerbation of disability and to improve or stop the decline in patient’s QoL |
In cases of refractory disease |
|
|
|
To save a patient from complete disability and to improve severely declined patient QoL |
In late stages of the disease in cases of rapid progression of patient disability |
All three strategies of HDIT +ASCT were applied: 43 patients (32.7%) underwent early transplantation; 82 (62.0%), conventional transplantation; and 7 (5.3%) received salvage/late transplantation.
Neurological evaluation was performed at baseline, at discharge, at 3, 6, 9, and 12 months, and every 6 months thereafter; and MRI examinations at baseline, at 6, and 12 months, and at the end of follow-up.
According to the EBMT criteria of response, patients with steady EDSS scores representing halt of disease progression or with improved EDSS scores representing subsidence of inflammation in the CNS were regarded as responding to treatment. Clinical improvement was defined as a 0.5-point decrease in EDSS score as compared to the baseline. Progression was defined as an increase of at least 0.5 points. Both had to be confirmed after 6 months. Clinical relapse was defined as the appearance of new symptoms or worsening of old symptoms of at least 24-hour duration, in the absence of fever in a previously (4 weeks) stable patient.
A BEAM or BEAM-modified conditioning regimen was used.
Median EDSS at baseline was 4.5 (range 1.5-8.5). The mean follow-up duration was 21 months (range 6-120 months).
A separate group of patients was identified to whom consolidation therapy (Mitoxantrone) after HDIT +ASCT was administered. These were patients with a number of risk factors. 34 patients were enrolled in this group. The preliminary analysis of treatment outcomes in this group will be conducted by December 2009.
Results
Adverse events
No transplant-related deaths were reported; transplantation procedure was well tolerated by the patients. Mobilization was successful in all cases with a median number of 2.1 x106/kg (range 1.5-5.5 x106/kg) CD34+ cells collected; no major clinical adverse events were observed during this phase. Unmanipulated grafts were infused without complications. Engraftment was uneventful, and no signs of an engraftment syndrome were reported. Median days with PMN <0.5x109 and Plt <50x109 were 8 (range from 5 to 11) and 10 days (from 2 to 26), respectively.
Common adverse effects following the immunoablative regimen were thrombocytopenia (100%), neutropenia (100%), fatigue (100%), anemia (80%), alopecia (80%), neutropenic fever (51.6%), hepatic toxicity grade I and II (48.1%), transient neurological dysfunction (22.2%), and enteropathy (18.5%). Documented sepsis was registered in one patient.
Clinical outcomes
Eighty-seven patients with a follow-up period of at least 9 months or longer were included in the clinical outcome analysis. All patients responded to the treatment. At 6 months post-transplant the following distribution of patients according to clinical response was observed: 46 patients (52.8%) achieved an objective improvement of neurological symptoms (defined as a 0.5 point decrease in the EDSS score as compared to the baseline and confirmed over 3 months), and 41 patients (47.2 %) had disease stabilization (steady EDSS level as compared to the baseline and confirmed over 3 months). At long-term follow-up the clinical response in 40 patients (50.6%) was classified as improvement; 34 patients (43.1%) remained stable. Two patients deteriorated to a worse score after 18 months of stabilization (SPMS and PPMS; conventional auto-HSCT), and one patient after 6 months of stabilization (SPMS, conventional auto-HSCT); 2 others progressed after 12 and 30 months of improvement (RRMS, early auto-HSCT and SPMM, conventional auto-HSCT, respectively). No active, new, or enlarging lesions were registered in patients without disease progression.
The analysis of clinical outcomes at long-term follow-up was performed separately for the groups after early, conventional, and salvage transplantation. Out of 24 patients who underwent early ASCT 14 patients (58.3%) improved, 9 patients (37.5) stabilized, and one patient (4.2%) progressed (after improvement). Out of 48 patients who underwent conventional ASCT 24 patients (50%) improved, 20 patients (42%) stabilized, and 4 (8%) progressed (3 after stabilization, and 1 after improvement). In the group of patients who underwent salvage ASCT 2 patients (29%) improved and 5 (71%) were stable during the follow-up.
Remarkably, nine patients improved dramatically (1.5 points by EDSS). Patients with different types of MS were observed in this group. As an illustration, in an SPMS patient with the baseline EDSS value of 6.0 we observed a 2.0 point decrease on the EDSS scale at 1 month post-transplant, an additional 1.5 point decrease at 6 months and stabilization with EDSS score of 1.5 at 18 months post-transplant. In another case, an RRMS patient with a baseline EDSS score of 4.5 experienced a decrease in EDSS to 2.0 at 1 month post-transplant with a further decrease to 1.0 at 3 months. The latter EDSS level remained stable throughout the entire follow-up period of 1.5 years. The PRMS patient with a baseline EDSS value of 6.0 improved at 3 months to EDSS of 4.5 and then showed further improvement at 30 months post-transplant to the EDSS score of 4.0. The EDSS score at the end of follow-up (6.5 years post-transplant) was 3.5. Finally, the PPMS patient with severe disease (EDSS score of 7.5) had a 1.5 point EDSS decrease and maintained this score during 3.5 years of follow-up.
Conclusions
- The results of our study demonstrate the benefits of HDIT +ASCT in patients with various types of MS. The transplantation procedure was well tolerated by patients, with no transplant-related deaths at all. All the patients included in the efficacy analysis responded to treatment. At long-term follow-up clinical response in terms of improvement or stabilization was registered in more than 90% of patients.
- The advantage of our study is that we included patients with different types of MS. In spite of some evidence that PPMS patients are less responsive to HDIT +ASCT as compared to both SPMS and RRMS, the information about the outcomes of HSCT in patients with various types of MS is limited. The results of our study confirm that transplantation is effective not only in SPMS and RRMS patients but in PPMS as well. Thus, patients with different types of MS might benefit from HDIT +ASCT.
- Another advantage of our study is the performance of early, conventional, or salvage transplantation, while most patients in the previous studies had late stages of MS. Our data supports the idea that HDIT +ASCT is more effective in young patients with early stages of rapidly progressing disease. In these patients, autoreactive T cells play a pivotal role in MS pathogenesis. HDIT ablates the patient's immune system and eradicates autoimmune T cells. It is followed by HSCT to restore the immune system, which is expected to become tolerant to autoantigens. Such "resetting" of the immune system is only effective at early stages of MS, particularly in relapsing-remitting MS. Later in the clinical course of the disease, processes of axonal degeneration prevail and the damage to CNS tissue is too significant to expect a neurological recovery after HDIT +ASCT. Indeed, failure of HDIT +ASCT to prevent progression of the disease when performed in the late stages has been demonstrated in both animal models [1] and in clinical studies [8, 2].
- The data obtained points to the feasibility of early, conventional, and salvage HDIT +ASCT in MS patients. Further studies should be done to investigate the clinical and patient-reported outcomes in MS patients receiving early, conventional, and salvage transplantation to better define treatment success. The concept of HDIT +ASCT in MS opens a new window of opportunity for treatment of this patient population.
References
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
" ["~DETAIL_TEXT"]=> string(16652) "Introduction
High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) is a promising approach to treatment of multiple sclerosis (MS) patients, since there are no effective treatment methods for this disease [4-7, 10]. HDCT+ASCT has been performed in more than 700 MS patients since 1995 all over the world. However, the patient selection criteria for HDIT +ASCT are still unclear and the proper selection of patients for transplantation remains the key issue [3, 9, 11]. In Russia more than 180 transplantations in MS patients were done within 10 years within a prospective Phase II multicenter trial coordinated by the Russian Cooperative Group for Cellular Therapy. The follow-up results of the patients who were enrolled in the Military Medical Academy (St. Petersburg) and Pirogov National Medical Surgical Center (Moscow) since 1999 are reported here. We focused on the efficacy of HDIT +ASCT in patients with different types and stages of MS. The patients underwent early, conventional, or salvage/late transplantation in accordance with the concept of HDIT +ASCT in MS [12, 13]. There are 3 strategies of HDIT +ASCT (Table 1). Early ASCT (in MS patients with EDSS 1.5–3.0) is performed soon after diagnosis in the case of primary refractory disease or poor prognosis. Conventional ASCT (EDSS 3.5–6.5) is performed in patients with secondary refractory disease. Salvage ASCT (EDSS 7.0–8.0) is an option in the case of high disease activity and rapid neurological deterioration in late stages of the disease.
Patients and Methods
132 MS patients were included in this study with a mean age of 33.0, and a male/female split of 58/74. The distribution according to the disease type was as follows: secondary progressive (SPMS): 57 patients, primary progressive (PPMS): 23, progressive-relapsing (PRMS): 9 and relapsing-remitting (RRMS): 43.
Criteria for patient selection were: age between 18 and 55 years, diagnosis of multiple sclerosis verified by clinical and laboratory findings, EDSS score 1.5–8.0, normal mental status, and absence of severe concomitant diseases.
The disease activity was determined either by magnetic resonance imaging scans displaying active lesions in the CNS (i.e., gadolinium-enhancing lesions, new or enlarging lesions on serial scans) or by clinical assessment showing rapid neurological deterioration, e.g., 0.5-point increase on the EDSS during the 6 months preceding enrollment.
Table 1. Classification of HDIT +ASCT in MS patients
|
Type of transplantation |
Pathogenetic goal |
Overall goal |
Timing |
|---|---|---|---|
|
Early transplantation |
To prevent the irreversible damage of the CNS by immunopathological process |
To stop the disease progression and |
In early stages of the disease in cases of poor prognosis |
|
Conventional transplantation |
|
To prevent the exacerbation of disability and to improve or stop the decline in patient’s QoL |
In cases of refractory disease |
|
|
|
To save a patient from complete disability and to improve severely declined patient QoL |
In late stages of the disease in cases of rapid progression of patient disability |
All three strategies of HDIT +ASCT were applied: 43 patients (32.7%) underwent early transplantation; 82 (62.0%), conventional transplantation; and 7 (5.3%) received salvage/late transplantation.
Neurological evaluation was performed at baseline, at discharge, at 3, 6, 9, and 12 months, and every 6 months thereafter; and MRI examinations at baseline, at 6, and 12 months, and at the end of follow-up.
According to the EBMT criteria of response, patients with steady EDSS scores representing halt of disease progression or with improved EDSS scores representing subsidence of inflammation in the CNS were regarded as responding to treatment. Clinical improvement was defined as a 0.5-point decrease in EDSS score as compared to the baseline. Progression was defined as an increase of at least 0.5 points. Both had to be confirmed after 6 months. Clinical relapse was defined as the appearance of new symptoms or worsening of old symptoms of at least 24-hour duration, in the absence of fever in a previously (4 weeks) stable patient.
A BEAM or BEAM-modified conditioning regimen was used.
Median EDSS at baseline was 4.5 (range 1.5-8.5). The mean follow-up duration was 21 months (range 6-120 months).
A separate group of patients was identified to whom consolidation therapy (Mitoxantrone) after HDIT +ASCT was administered. These were patients with a number of risk factors. 34 patients were enrolled in this group. The preliminary analysis of treatment outcomes in this group will be conducted by December 2009.
Results
Adverse events
No transplant-related deaths were reported; transplantation procedure was well tolerated by the patients. Mobilization was successful in all cases with a median number of 2.1 x106/kg (range 1.5-5.5 x106/kg) CD34+ cells collected; no major clinical adverse events were observed during this phase. Unmanipulated grafts were infused without complications. Engraftment was uneventful, and no signs of an engraftment syndrome were reported. Median days with PMN <0.5x109 and Plt <50x109 were 8 (range from 5 to 11) and 10 days (from 2 to 26), respectively.
Common adverse effects following the immunoablative regimen were thrombocytopenia (100%), neutropenia (100%), fatigue (100%), anemia (80%), alopecia (80%), neutropenic fever (51.6%), hepatic toxicity grade I and II (48.1%), transient neurological dysfunction (22.2%), and enteropathy (18.5%). Documented sepsis was registered in one patient.
Clinical outcomes
Eighty-seven patients with a follow-up period of at least 9 months or longer were included in the clinical outcome analysis. All patients responded to the treatment. At 6 months post-transplant the following distribution of patients according to clinical response was observed: 46 patients (52.8%) achieved an objective improvement of neurological symptoms (defined as a 0.5 point decrease in the EDSS score as compared to the baseline and confirmed over 3 months), and 41 patients (47.2 %) had disease stabilization (steady EDSS level as compared to the baseline and confirmed over 3 months). At long-term follow-up the clinical response in 40 patients (50.6%) was classified as improvement; 34 patients (43.1%) remained stable. Two patients deteriorated to a worse score after 18 months of stabilization (SPMS and PPMS; conventional auto-HSCT), and one patient after 6 months of stabilization (SPMS, conventional auto-HSCT); 2 others progressed after 12 and 30 months of improvement (RRMS, early auto-HSCT and SPMM, conventional auto-HSCT, respectively). No active, new, or enlarging lesions were registered in patients without disease progression.
The analysis of clinical outcomes at long-term follow-up was performed separately for the groups after early, conventional, and salvage transplantation. Out of 24 patients who underwent early ASCT 14 patients (58.3%) improved, 9 patients (37.5) stabilized, and one patient (4.2%) progressed (after improvement). Out of 48 patients who underwent conventional ASCT 24 patients (50%) improved, 20 patients (42%) stabilized, and 4 (8%) progressed (3 after stabilization, and 1 after improvement). In the group of patients who underwent salvage ASCT 2 patients (29%) improved and 5 (71%) were stable during the follow-up.
Remarkably, nine patients improved dramatically (1.5 points by EDSS). Patients with different types of MS were observed in this group. As an illustration, in an SPMS patient with the baseline EDSS value of 6.0 we observed a 2.0 point decrease on the EDSS scale at 1 month post-transplant, an additional 1.5 point decrease at 6 months and stabilization with EDSS score of 1.5 at 18 months post-transplant. In another case, an RRMS patient with a baseline EDSS score of 4.5 experienced a decrease in EDSS to 2.0 at 1 month post-transplant with a further decrease to 1.0 at 3 months. The latter EDSS level remained stable throughout the entire follow-up period of 1.5 years. The PRMS patient with a baseline EDSS value of 6.0 improved at 3 months to EDSS of 4.5 and then showed further improvement at 30 months post-transplant to the EDSS score of 4.0. The EDSS score at the end of follow-up (6.5 years post-transplant) was 3.5. Finally, the PPMS patient with severe disease (EDSS score of 7.5) had a 1.5 point EDSS decrease and maintained this score during 3.5 years of follow-up.
Conclusions
- The results of our study demonstrate the benefits of HDIT +ASCT in patients with various types of MS. The transplantation procedure was well tolerated by patients, with no transplant-related deaths at all. All the patients included in the efficacy analysis responded to treatment. At long-term follow-up clinical response in terms of improvement or stabilization was registered in more than 90% of patients.
- The advantage of our study is that we included patients with different types of MS. In spite of some evidence that PPMS patients are less responsive to HDIT +ASCT as compared to both SPMS and RRMS, the information about the outcomes of HSCT in patients with various types of MS is limited. The results of our study confirm that transplantation is effective not only in SPMS and RRMS patients but in PPMS as well. Thus, patients with different types of MS might benefit from HDIT +ASCT.
- Another advantage of our study is the performance of early, conventional, or salvage transplantation, while most patients in the previous studies had late stages of MS. Our data supports the idea that HDIT +ASCT is more effective in young patients with early stages of rapidly progressing disease. In these patients, autoreactive T cells play a pivotal role in MS pathogenesis. HDIT ablates the patient's immune system and eradicates autoimmune T cells. It is followed by HSCT to restore the immune system, which is expected to become tolerant to autoantigens. Such "resetting" of the immune system is only effective at early stages of MS, particularly in relapsing-remitting MS. Later in the clinical course of the disease, processes of axonal degeneration prevail and the damage to CNS tissue is too significant to expect a neurological recovery after HDIT +ASCT. Indeed, failure of HDIT +ASCT to prevent progression of the disease when performed in the late stages has been demonstrated in both animal models [1] and in clinical studies [8, 2].
- The data obtained points to the feasibility of early, conventional, and salvage HDIT +ASCT in MS patients. Further studies should be done to investigate the clinical and patient-reported outcomes in MS patients receiving early, conventional, and salvage transplantation to better define treatment success. The concept of HDIT +ASCT in MS opens a new window of opportunity for treatment of this patient population.
References
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
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Новик<sup>1</sup>, Алексей Н. Кузнецов<sup>1,2</sup>, Владимир Я. Мельниченко<sup>1</sup>, Денис А. Федоренко<sup>1</sup>, Tатьяна И. Ионова<sup>3</sup>, Кира А. Курбатова<sup>3</sup></span> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(316) "Aндрей A. Новик1, Алексей Н. Кузнецов1,2, Владимир Я. Мельниченко1, Денис А. Федоренко1, Tатьяна И. Ионова3, Кира А. Курбатова3
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18307" ["VALUE"]=> array(2) { ["TEXT"]=> string(1287) "<p class="bodytext"><sup>1</sup>Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; <sup>2</sup>Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; <sup>3</sup>Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия<br /><br /><b>Контакт</b><br> А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.rgvxg48Dqemp2vy');">ncrtc04@<span style="display:none;">spam is bad</span>mail.ru</a>, <a href="javascript:linkTo_UnCryptMailto('qempxs.ruspgDcerhib2vy');">nqolc@<span style="display:none;">spam is bad</span>yandex.ru</a> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1105) "1Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; 2Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; 3Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия
Контакт
А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия
E-mail: ncrtc04@mail.ru, nqolc@yandex.ru
Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Ключевые слова
рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения
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Correspondence
Professor Tatyana I. Ionova, Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., 191014 St. Petersburg, Russia
E-mail: tion16@mail.ru
High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) is a promising approach to the treatment of multiple sclerosis (MS) patients. The data obtained points to the feasibility of early, conventional, and salvage HDIT +ASCT in MS patients. Further studies should be done to investigate clinical and patient-reported outcomes in MS patients receiving early, conventional, and salvage transplantation to better define treatment success. The concept of HDIT +ASCT in MS opens a new window of opportunity for treatment of this patient population.
Keywords
multiple sclerosis, autologous stem cell transplantation, long-term clinical outcomes, early ASCT, conventional ASCT, salvage ASCT
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Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). В настоящее время в мире выполнено более 700 трансплантаций больным с различными формами РС. Безопасность и эффективность метода изучена в международных многоцентровых исследованиях. К нерешенным вопросам ВИСТ+ТСКК относятся следующие: показания, методы трансплантации, режимы кондиционирования, деплеция Т-лимфоцитов, фармакоэкономическое обоснование и др. [3, 9, 11].<br> <br> Разработана концепция ВИСТ+ТКСК при РС, включающая следующие положения: содержание метода, основные показания, методика проведения трансплантации, общий алгоритм, направления дальнейших исследований. Основные положения концепции подтверждены результатами проспективного многоцентрового исследования Российской кооперативной группы клеточной терапии изучения эффективности ВИСТ+ТКСК у больных различными формами РС. <br> <br> В рамках концепции выделено две принципиальные цели лечения больных РС. Первая из них патогенетическая – остановить прогрессирование заболевания и предотвратить появление новых очагов демиелинизации в ЦНС за счет воздействия на иммунопатологический процесс на различных уровнях. Вторая цель, основная или конечная, состоит в сохранении и, по возможности, в улучшении качества жизни больных. Данные положения основаны на теории принятия решений в клинической медицине, согласно которой в формализованном виде существует три возможных цели лечения больного: <br> <br> I – излечение с учетом качества жизни больного после выздоровления, <br> II – увеличение продолжительности жизни больного с учетом ее качества<br> III – улучшение качества жизни больного. <br> <br> При РС, хроническом неизлечимом заболевании, в большинстве случаев не снижающем продолжительность жизни больного, максимально возможное восстановление и сохранение параметров качества жизни является приоритетной целью лечения. Вследствие этого, наряду с традиционными лабораторными и инструментальными тестами, описывающими изменения в течении патологического процесса на фоне терапии, к ключевым критериям эффективности лечения РС следует отнести и показатели качества жизни больного, отражающие сложный комплекс физических, психологических и социальных детерминант, свойственных конкретному индивидууму. <br> <br> Учитывая вышесказанное, в рамках концепции выделены 3 вида трансплантации, отличающиеся по целям и времени проведения операции [12, 13]<br> <br> <b>Ранняя трансплантация</b><br> 1. Патогенетическая цель – предупредить развитие необратимых изменений в ЦНС в результате иммунопатологического процесса.<br> 2. Основная цель – сохранить качество жизни больного, предотвратить формирование инвалидизации. <br> 3. Время проведения – в дебюте заболевания.<br> <br> <b>Этапная трансплантация</b><br> 4. Патогенетическая цель – остановить прогрессирование заболевания на фоне самоподдерживающегося иммунопатологического процесса, имеющихся очагов необратимых изменений и частично утраченных функций, предупредить появление новых очагов поражения.<br> 5. Основная цель – улучшить качество жизни больного и сохранить его на максимально возможном уровне, предупредить углубление инвалидизации пациента.<br> 6. Время проведения – на различных этапах прогрессирования РС при выходе заболевания из-под контроля традиционных методов лечения.<br> <br> <b>Трансплантация спасения<br> </b>7. Патогенетическая цель – остановить прогрессирование заболевания на фоне большого количества очагов необратимых изменений и существенно нарушенных функций, предупредить появление новых очагов поражения.<br> 8. Основная цель – сохранить качество жизни больного на максимально возможном уровне, предотвратить наступление критической инвалидизации.<br> 9. Время проведения – в далеко зашедшей стадии заболевания при высокой активности иммунопатологического процесса, быстром прогрессировании инвалидизации больного. </p> <p class="bodytext"> В данном докладе представлены результаты исследования безопасности и эффективности ВИСТ+ТКСК у 132 больных РС, которым ВИСТ+ТКСК проведена в Военно-медицинской академии (Санкт-Петербург) и Национальном медико-хирургическом центре им. Н.И. Пирогова (Москва), начиная с 1999 года. В исследование включено 58 мужчин и 74 женщины; средний возраст – 33 года. У 57 пациентов была диагностирована вторично-прогрессирующая форма заболевания, у 23 – первично-прогрессирующая, у 9 – прогрессирующе-рецидивирующая и у 43 – рецидивирующая ремитирующая. Выделены три группы пациентов в зависимости от вида трансплантации: ранняя трансплантация проводилась при EDSS от 1,5 до 3,0; этапная трансплантация - при EDSS от 3,5 до 6,5; трансплантация спасения - при EDSS от 7,0 до 8,5. 83 пациентам была проведена этапная ВИСТ+ТКСК; 43 – ранняя трансплантация; 7 – трансплантация спасения. Для кондиционирования использовали режимы BEAM или mini-BEAM. Эффект ВИСТ+ТКСК оценивали по изменению степени инвалидизации больного и активности заболевания.<br> <br> Отдельно была выделена группа больных, которым проводили консолидирующую терапию (митоксантрон) после ВИСТ+ТКСК. В эту группу вошли пациенты, имеющие факторы риска. В настоящее время данная группа включает 34 пациента; анализ результатов лечения в этой группе будет проведен в декабре 2009г.<br> <br> При проведении ВИСТ+ТКСК не было летальных исходов, связанных с трансплантацией, а также тяжелых непрогнозируемых осложнений. У всех больных зарегистрирован ответ на лечение: у половины больных было зарегистрировано клиническое улучшение; у остальных – стабилизация состояния. По данным МРТ у всех больных имелось либо улучшение, либо стабилизация процесса. В отдаленные сроки после ВИСТ+ТКСК (2 года и более) у подавляющего большинства больных (более 90%) наблюдали клиническое улучшение или стабилизацию заболевания. По данным магнитно-резонансной томографии отсутствие активности заболевания зарегистрировано у всех больных с клиническим улучшением или стабилизацией. Особого внимания заслуживает группа больных, которым проведена ранняя ВИСТ+ТКСК, и группа больных, у которых трансплантацию проводили с применением немиелоаблативных режимов кондиционирования. <br> <br> ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области. </p> <h3>Литература</h3> <p class="bodytext"> 1. <a href="http://bloodjournal.hematologylibrary.org/cgi/reprint/91/7/2609" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Burt RK, et al. Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis. Blood. 1998;91:2609–2616</u></a><u>.</u> </p> <p class="bodytext"> 2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150. </p> <p class="bodytext"> 3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382. </p> <p class="bodytext"> 4. <a href="http://www.nature.com/bmt/journal/v20/n8/pdf/1700944a.pdf" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Fassas A, et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997;20:631-638</u></a><u>.</u> </p> <p class="bodytext"> 5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090. </p> <p class="bodytext"> 6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7. </p> <p class="bodytext"> 7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005. </p> <p class="bodytext"> 8. <a href="http://bloodjournal.hematologylibrary.org/cgi/content/full/102/7/2364" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Nash RA, et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood. 2003;102:2364-2372. doi: 10.1182/blood-2002-12-3908</u></a><u>.</u> </p> <p class="bodytext"> 9. <a href="http://bloodjournal.hematologylibrary.org/cgi/content/full/105/6/2601" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Saccardi R, et al. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood. 2005;105:2601-2607. doi: 10.1182/blood-2004-08-3205</u></a><u>.</u> </p> <p class="bodytext"> 10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823. </p> <p class="bodytext"> 11. <a href="typo3/1-2-shevchenko-et-al-2008dec3.html" title="Opens external link in new window" class="external-link-new-window"><u>Shevchenko Y, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis. Cellular Therapy and Transplantation (CTT). 2008;1:2. doi: 10.3205/ctt-2008-en-000025.01</u></a>. </p> <p class="bodytext"> 12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346. </p> <p class="bodytext"> 13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(16499) "
Традиционные методы иммуномодулирующей и иммуносупрессивной терапии рассеянного склероза (РС) не позволяют достичь выраженного и длительного терапевтического эффекта [4-7, 10]. Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). В настоящее время в мире выполнено более 700 трансплантаций больным с различными формами РС. Безопасность и эффективность метода изучена в международных многоцентровых исследованиях. К нерешенным вопросам ВИСТ+ТСКК относятся следующие: показания, методы трансплантации, режимы кондиционирования, деплеция Т-лимфоцитов, фармакоэкономическое обоснование и др. [3, 9, 11].
Разработана концепция ВИСТ+ТКСК при РС, включающая следующие положения: содержание метода, основные показания, методика проведения трансплантации, общий алгоритм, направления дальнейших исследований. Основные положения концепции подтверждены результатами проспективного многоцентрового исследования Российской кооперативной группы клеточной терапии изучения эффективности ВИСТ+ТКСК у больных различными формами РС.
В рамках концепции выделено две принципиальные цели лечения больных РС. Первая из них патогенетическая – остановить прогрессирование заболевания и предотвратить появление новых очагов демиелинизации в ЦНС за счет воздействия на иммунопатологический процесс на различных уровнях. Вторая цель, основная или конечная, состоит в сохранении и, по возможности, в улучшении качества жизни больных. Данные положения основаны на теории принятия решений в клинической медицине, согласно которой в формализованном виде существует три возможных цели лечения больного:
I – излечение с учетом качества жизни больного после выздоровления,
II – увеличение продолжительности жизни больного с учетом ее качества
III – улучшение качества жизни больного.
При РС, хроническом неизлечимом заболевании, в большинстве случаев не снижающем продолжительность жизни больного, максимально возможное восстановление и сохранение параметров качества жизни является приоритетной целью лечения. Вследствие этого, наряду с традиционными лабораторными и инструментальными тестами, описывающими изменения в течении патологического процесса на фоне терапии, к ключевым критериям эффективности лечения РС следует отнести и показатели качества жизни больного, отражающие сложный комплекс физических, психологических и социальных детерминант, свойственных конкретному индивидууму.
Учитывая вышесказанное, в рамках концепции выделены 3 вида трансплантации, отличающиеся по целям и времени проведения операции [12, 13]
Ранняя трансплантация
1. Патогенетическая цель – предупредить развитие необратимых изменений в ЦНС в результате иммунопатологического процесса.
2. Основная цель – сохранить качество жизни больного, предотвратить формирование инвалидизации.
3. Время проведения – в дебюте заболевания.
Этапная трансплантация
4. Патогенетическая цель – остановить прогрессирование заболевания на фоне самоподдерживающегося иммунопатологического процесса, имеющихся очагов необратимых изменений и частично утраченных функций, предупредить появление новых очагов поражения.
5. Основная цель – улучшить качество жизни больного и сохранить его на максимально возможном уровне, предупредить углубление инвалидизации пациента.
6. Время проведения – на различных этапах прогрессирования РС при выходе заболевания из-под контроля традиционных методов лечения.
Трансплантация спасения
7. Патогенетическая цель – остановить прогрессирование заболевания на фоне большого количества очагов необратимых изменений и существенно нарушенных функций, предупредить появление новых очагов поражения.
8. Основная цель – сохранить качество жизни больного на максимально возможном уровне, предотвратить наступление критической инвалидизации.
9. Время проведения – в далеко зашедшей стадии заболевания при высокой активности иммунопатологического процесса, быстром прогрессировании инвалидизации больного.
В данном докладе представлены результаты исследования безопасности и эффективности ВИСТ+ТКСК у 132 больных РС, которым ВИСТ+ТКСК проведена в Военно-медицинской академии (Санкт-Петербург) и Национальном медико-хирургическом центре им. Н.И. Пирогова (Москва), начиная с 1999 года. В исследование включено 58 мужчин и 74 женщины; средний возраст – 33 года. У 57 пациентов была диагностирована вторично-прогрессирующая форма заболевания, у 23 – первично-прогрессирующая, у 9 – прогрессирующе-рецидивирующая и у 43 – рецидивирующая ремитирующая. Выделены три группы пациентов в зависимости от вида трансплантации: ранняя трансплантация проводилась при EDSS от 1,5 до 3,0; этапная трансплантация - при EDSS от 3,5 до 6,5; трансплантация спасения - при EDSS от 7,0 до 8,5. 83 пациентам была проведена этапная ВИСТ+ТКСК; 43 – ранняя трансплантация; 7 – трансплантация спасения. Для кондиционирования использовали режимы BEAM или mini-BEAM. Эффект ВИСТ+ТКСК оценивали по изменению степени инвалидизации больного и активности заболевания.
Отдельно была выделена группа больных, которым проводили консолидирующую терапию (митоксантрон) после ВИСТ+ТКСК. В эту группу вошли пациенты, имеющие факторы риска. В настоящее время данная группа включает 34 пациента; анализ результатов лечения в этой группе будет проведен в декабре 2009г.
При проведении ВИСТ+ТКСК не было летальных исходов, связанных с трансплантацией, а также тяжелых непрогнозируемых осложнений. У всех больных зарегистрирован ответ на лечение: у половины больных было зарегистрировано клиническое улучшение; у остальных – стабилизация состояния. По данным МРТ у всех больных имелось либо улучшение, либо стабилизация процесса. В отдаленные сроки после ВИСТ+ТКСК (2 года и более) у подавляющего большинства больных (более 90%) наблюдали клиническое улучшение или стабилизацию заболевания. По данным магнитно-резонансной томографии отсутствие активности заболевания зарегистрировано у всех больных с клиническим улучшением или стабилизацией. Особого внимания заслуживает группа больных, которым проведена ранняя ВИСТ+ТКСК, и группа больных, у которых трансплантацию проводили с применением немиелоаблативных режимов кондиционирования.
ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Литература
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
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Novik<sup>1</sup>, Aleksey N. Kuznetsov<sup>1</sup>, Vladimir Y. Melnichenko<sup>1</sup>, Denis A. Fedorenko<sup>1</sup>, Tatyana I. Ionova<sup>2</sup>, Kira A. Kurbatova<sup>2</sup></p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(199) "Andrei A. Novik1, Aleksey N. Kuznetsov1, Vladimir Y. Melnichenko1, Denis A. Fedorenko1, Tatyana I. Ionova2, Kira A. Kurbatova2
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Keywords
multiple sclerosis, autologous stem cell transplantation, long-term clinical outcomes, early ASCT, conventional ASCT, salvage ASCT
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(775) "High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) is a promising approach to the treatment of multiple sclerosis (MS) patients. The data obtained points to the feasibility of early, conventional, and salvage HDIT +ASCT in MS patients. Further studies should be done to investigate clinical and patient-reported outcomes in MS patients receiving early, conventional, and salvage transplantation to better define treatment success. The concept of HDIT +ASCT in MS opens a new window of opportunity for treatment of this patient population.
Keywords
multiple sclerosis, autologous stem cell transplantation, long-term clinical outcomes, early ASCT, conventional ASCT, salvage ASCT
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Correspondence
Professor Tatyana I. Ionova, Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., 191014 St. Petersburg, Russia
E-mail: tion16@mail.ru
1Pirogov National Medical Surgical Center, Moscow, Russia; 2Multinational Center for Quality of Life Research, Saint Petersburg, Russia
Correspondence
Professor Tatyana I. Ionova, Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., 191014 St. Petersburg, Russia
E-mail: tion16@mail.ru
Aндрей A. Новик1, Алексей Н. Кузнецов1,2, Владимир Я. Мельниченко1, Денис А. Федоренко1, Tатьяна И. Ионова3, Кира А. Курбатова3
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ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.<br /><br /><h3>Ключевые слова</h3> <p>рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1515) "Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Ключевые слова
рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(1515) "Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Ключевые слова
рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения
" } ["ORGANIZATION_RU"]=> array(37) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18307" ["VALUE"]=> array(2) { ["TEXT"]=> string(1287) "<p class="bodytext"><sup>1</sup>Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; <sup>2</sup>Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; <sup>3</sup>Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия<br /><br /><b>Контакт</b><br> А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.rgvxg48Dqemp2vy');">ncrtc04@<span style="display:none;">spam is bad</span>mail.ru</a>, <a href="javascript:linkTo_UnCryptMailto('qempxs.ruspgDcerhib2vy');">nqolc@<span style="display:none;">spam is bad</span>yandex.ru</a> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1105) "1Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; 2Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; 3Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия
Контакт
А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия
E-mail: ncrtc04@mail.ru, nqolc@yandex.ru
1Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; 2Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; 3Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия
Контакт
А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия
E-mail: ncrtc04@mail.ru, nqolc@yandex.ru
Традиционные методы иммуномодулирующей и иммуносупрессивной терапии рассеянного склероза (РС) не позволяют достичь выраженного и длительного терапевтического эффекта [4-7, 10]. Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). В настоящее время в мире выполнено более 700 трансплантаций больным с различными формами РС. Безопасность и эффективность метода изучена в международных многоцентровых исследованиях. К нерешенным вопросам ВИСТ+ТСКК относятся следующие: показания, методы трансплантации, режимы кондиционирования, деплеция Т-лимфоцитов, фармакоэкономическое обоснование и др. [3, 9, 11].
Разработана концепция ВИСТ+ТКСК при РС, включающая следующие положения: содержание метода, основные показания, методика проведения трансплантации, общий алгоритм, направления дальнейших исследований. Основные положения концепции подтверждены результатами проспективного многоцентрового исследования Российской кооперативной группы клеточной терапии изучения эффективности ВИСТ+ТКСК у больных различными формами РС.
В рамках концепции выделено две принципиальные цели лечения больных РС. Первая из них патогенетическая – остановить прогрессирование заболевания и предотвратить появление новых очагов демиелинизации в ЦНС за счет воздействия на иммунопатологический процесс на различных уровнях. Вторая цель, основная или конечная, состоит в сохранении и, по возможности, в улучшении качества жизни больных. Данные положения основаны на теории принятия решений в клинической медицине, согласно которой в формализованном виде существует три возможных цели лечения больного:
I – излечение с учетом качества жизни больного после выздоровления,
II – увеличение продолжительности жизни больного с учетом ее качества
III – улучшение качества жизни больного.
При РС, хроническом неизлечимом заболевании, в большинстве случаев не снижающем продолжительность жизни больного, максимально возможное восстановление и сохранение параметров качества жизни является приоритетной целью лечения. Вследствие этого, наряду с традиционными лабораторными и инструментальными тестами, описывающими изменения в течении патологического процесса на фоне терапии, к ключевым критериям эффективности лечения РС следует отнести и показатели качества жизни больного, отражающие сложный комплекс физических, психологических и социальных детерминант, свойственных конкретному индивидууму.
Учитывая вышесказанное, в рамках концепции выделены 3 вида трансплантации, отличающиеся по целям и времени проведения операции [12, 13]
Ранняя трансплантация
1. Патогенетическая цель – предупредить развитие необратимых изменений в ЦНС в результате иммунопатологического процесса.
2. Основная цель – сохранить качество жизни больного, предотвратить формирование инвалидизации.
3. Время проведения – в дебюте заболевания.
Этапная трансплантация
4. Патогенетическая цель – остановить прогрессирование заболевания на фоне самоподдерживающегося иммунопатологического процесса, имеющихся очагов необратимых изменений и частично утраченных функций, предупредить появление новых очагов поражения.
5. Основная цель – улучшить качество жизни больного и сохранить его на максимально возможном уровне, предупредить углубление инвалидизации пациента.
6. Время проведения – на различных этапах прогрессирования РС при выходе заболевания из-под контроля традиционных методов лечения.
Трансплантация спасения
7. Патогенетическая цель – остановить прогрессирование заболевания на фоне большого количества очагов необратимых изменений и существенно нарушенных функций, предупредить появление новых очагов поражения.
8. Основная цель – сохранить качество жизни больного на максимально возможном уровне, предотвратить наступление критической инвалидизации.
9. Время проведения – в далеко зашедшей стадии заболевания при высокой активности иммунопатологического процесса, быстром прогрессировании инвалидизации больного.
В данном докладе представлены результаты исследования безопасности и эффективности ВИСТ+ТКСК у 132 больных РС, которым ВИСТ+ТКСК проведена в Военно-медицинской академии (Санкт-Петербург) и Национальном медико-хирургическом центре им. Н.И. Пирогова (Москва), начиная с 1999 года. В исследование включено 58 мужчин и 74 женщины; средний возраст – 33 года. У 57 пациентов была диагностирована вторично-прогрессирующая форма заболевания, у 23 – первично-прогрессирующая, у 9 – прогрессирующе-рецидивирующая и у 43 – рецидивирующая ремитирующая. Выделены три группы пациентов в зависимости от вида трансплантации: ранняя трансплантация проводилась при EDSS от 1,5 до 3,0; этапная трансплантация - при EDSS от 3,5 до 6,5; трансплантация спасения - при EDSS от 7,0 до 8,5. 83 пациентам была проведена этапная ВИСТ+ТКСК; 43 – ранняя трансплантация; 7 – трансплантация спасения. Для кондиционирования использовали режимы BEAM или mini-BEAM. Эффект ВИСТ+ТКСК оценивали по изменению степени инвалидизации больного и активности заболевания.
Отдельно была выделена группа больных, которым проводили консолидирующую терапию (митоксантрон) после ВИСТ+ТКСК. В эту группу вошли пациенты, имеющие факторы риска. В настоящее время данная группа включает 34 пациента; анализ результатов лечения в этой группе будет проведен в декабре 2009г.
При проведении ВИСТ+ТКСК не было летальных исходов, связанных с трансплантацией, а также тяжелых непрогнозируемых осложнений. У всех больных зарегистрирован ответ на лечение: у половины больных было зарегистрировано клиническое улучшение; у остальных – стабилизация состояния. По данным МРТ у всех больных имелось либо улучшение, либо стабилизация процесса. В отдаленные сроки после ВИСТ+ТКСК (2 года и более) у подавляющего большинства больных (более 90%) наблюдали клиническое улучшение или стабилизацию заболевания. По данным магнитно-резонансной томографии отсутствие активности заболевания зарегистрировано у всех больных с клиническим улучшением или стабилизацией. Особого внимания заслуживает группа больных, которым проведена ранняя ВИСТ+ТКСК, и группа больных, у которых трансплантацию проводили с применением немиелоаблативных режимов кондиционирования.
ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Литература
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
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Традиционные методы иммуномодулирующей и иммуносупрессивной терапии рассеянного склероза (РС) не позволяют достичь выраженного и длительного терапевтического эффекта [4-7, 10]. Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). В настоящее время в мире выполнено более 700 трансплантаций больным с различными формами РС. Безопасность и эффективность метода изучена в международных многоцентровых исследованиях. К нерешенным вопросам ВИСТ+ТСКК относятся следующие: показания, методы трансплантации, режимы кондиционирования, деплеция Т-лимфоцитов, фармакоэкономическое обоснование и др. [3, 9, 11].
Разработана концепция ВИСТ+ТКСК при РС, включающая следующие положения: содержание метода, основные показания, методика проведения трансплантации, общий алгоритм, направления дальнейших исследований. Основные положения концепции подтверждены результатами проспективного многоцентрового исследования Российской кооперативной группы клеточной терапии изучения эффективности ВИСТ+ТКСК у больных различными формами РС.
В рамках концепции выделено две принципиальные цели лечения больных РС. Первая из них патогенетическая – остановить прогрессирование заболевания и предотвратить появление новых очагов демиелинизации в ЦНС за счет воздействия на иммунопатологический процесс на различных уровнях. Вторая цель, основная или конечная, состоит в сохранении и, по возможности, в улучшении качества жизни больных. Данные положения основаны на теории принятия решений в клинической медицине, согласно которой в формализованном виде существует три возможных цели лечения больного:
I – излечение с учетом качества жизни больного после выздоровления,
II – увеличение продолжительности жизни больного с учетом ее качества
III – улучшение качества жизни больного.
При РС, хроническом неизлечимом заболевании, в большинстве случаев не снижающем продолжительность жизни больного, максимально возможное восстановление и сохранение параметров качества жизни является приоритетной целью лечения. Вследствие этого, наряду с традиционными лабораторными и инструментальными тестами, описывающими изменения в течении патологического процесса на фоне терапии, к ключевым критериям эффективности лечения РС следует отнести и показатели качества жизни больного, отражающие сложный комплекс физических, психологических и социальных детерминант, свойственных конкретному индивидууму.
Учитывая вышесказанное, в рамках концепции выделены 3 вида трансплантации, отличающиеся по целям и времени проведения операции [12, 13]
Ранняя трансплантация
1. Патогенетическая цель – предупредить развитие необратимых изменений в ЦНС в результате иммунопатологического процесса.
2. Основная цель – сохранить качество жизни больного, предотвратить формирование инвалидизации.
3. Время проведения – в дебюте заболевания.
Этапная трансплантация
4. Патогенетическая цель – остановить прогрессирование заболевания на фоне самоподдерживающегося иммунопатологического процесса, имеющихся очагов необратимых изменений и частично утраченных функций, предупредить появление новых очагов поражения.
5. Основная цель – улучшить качество жизни больного и сохранить его на максимально возможном уровне, предупредить углубление инвалидизации пациента.
6. Время проведения – на различных этапах прогрессирования РС при выходе заболевания из-под контроля традиционных методов лечения.
Трансплантация спасения
7. Патогенетическая цель – остановить прогрессирование заболевания на фоне большого количества очагов необратимых изменений и существенно нарушенных функций, предупредить появление новых очагов поражения.
8. Основная цель – сохранить качество жизни больного на максимально возможном уровне, предотвратить наступление критической инвалидизации.
9. Время проведения – в далеко зашедшей стадии заболевания при высокой активности иммунопатологического процесса, быстром прогрессировании инвалидизации больного.
В данном докладе представлены результаты исследования безопасности и эффективности ВИСТ+ТКСК у 132 больных РС, которым ВИСТ+ТКСК проведена в Военно-медицинской академии (Санкт-Петербург) и Национальном медико-хирургическом центре им. Н.И. Пирогова (Москва), начиная с 1999 года. В исследование включено 58 мужчин и 74 женщины; средний возраст – 33 года. У 57 пациентов была диагностирована вторично-прогрессирующая форма заболевания, у 23 – первично-прогрессирующая, у 9 – прогрессирующе-рецидивирующая и у 43 – рецидивирующая ремитирующая. Выделены три группы пациентов в зависимости от вида трансплантации: ранняя трансплантация проводилась при EDSS от 1,5 до 3,0; этапная трансплантация - при EDSS от 3,5 до 6,5; трансплантация спасения - при EDSS от 7,0 до 8,5. 83 пациентам была проведена этапная ВИСТ+ТКСК; 43 – ранняя трансплантация; 7 – трансплантация спасения. Для кондиционирования использовали режимы BEAM или mini-BEAM. Эффект ВИСТ+ТКСК оценивали по изменению степени инвалидизации больного и активности заболевания.
Отдельно была выделена группа больных, которым проводили консолидирующую терапию (митоксантрон) после ВИСТ+ТКСК. В эту группу вошли пациенты, имеющие факторы риска. В настоящее время данная группа включает 34 пациента; анализ результатов лечения в этой группе будет проведен в декабре 2009г.
При проведении ВИСТ+ТКСК не было летальных исходов, связанных с трансплантацией, а также тяжелых непрогнозируемых осложнений. У всех больных зарегистрирован ответ на лечение: у половины больных было зарегистрировано клиническое улучшение; у остальных – стабилизация состояния. По данным МРТ у всех больных имелось либо улучшение, либо стабилизация процесса. В отдаленные сроки после ВИСТ+ТКСК (2 года и более) у подавляющего большинства больных (более 90%) наблюдали клиническое улучшение или стабилизацию заболевания. По данным магнитно-резонансной томографии отсутствие активности заболевания зарегистрировано у всех больных с клиническим улучшением или стабилизацией. Особого внимания заслуживает группа больных, которым проведена ранняя ВИСТ+ТКСК, и группа больных, у которых трансплантацию проводили с применением немиелоаблативных режимов кондиционирования.
ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Литература
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
" } } } [6]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "76" ["~IBLOCK_SECTION_ID"]=> string(2) "76" ["ID"]=> string(4) "1372" ["~ID"]=> string(4) "1372" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(43) "Возможности АТСК при РС" ["~NAME"]=> string(43) "Возможности АТСК при РС" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(19) "22.09.2017 15:26:31" ["~TIMESTAMP_X"]=> string(19) "22.09.2017 15:26:31" ["DETAIL_PAGE_URL"]=> string(59) "/ru/archive/tom-2-nomer-2-6/stati/vozmozhnosti-atsk-pri-rs/" ["~DETAIL_PAGE_URL"]=> string(59) "/ru/archive/tom-2-nomer-2-6/stati/vozmozhnosti-atsk-pri-rs/" ["LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["~LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["DETAIL_TEXT"]=> string(13592) "Introduction
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, producing multifocal neurological symptoms caused by nerve demyelination and progressive neurodegeneration. The pathological hallmark of MS is multiple demyelinated plaques (sharply defined areas of demyelination) in the white matter and widely distributed areas of degeneration [7, 10]. The core process in MS is inflammatory, with T cells and their mediators triggering myelin injury; additionally, oligodendrocyte/myelin damage is often mediated by autoantibody fixation with consequent complement activation. Therefore, multiple sclerosis is an autoimmune condition with a complex pathogenesis involving cellular and humoral immune response activation [3].
Presently in MS four types of neural tissue injury can be distinguished [9]. Two of them are caused by activation of cellular and humoral immune system compartments, and the others are characterized by degenerative changes in oligodendrocytes with primary or distal injury. These four types can occur at the different stages of MS. The present conception of MS pathogenesis encompasses two basic mechanisms – autoimmune inflammation and neurodegenerative changes [1, 11].
Multiple studies and clinical observations showed the progressive decrease of brain tissue total volume in MS [4, 12, 15, 16]. The beginning of the disease course is characterized by repeated episodes of inflammation with new contrast-accumulating T2 lesions revealed by MRI. However a considerable amount of recent data suggests the importance of degenerative changes at the earliest stages of the disease [4]. Today the pathogenesis of MS is considered to be a complex process with the inflammatory component being only a part of the general process.
Even small T2 lesions can be associated with general atrophy, though within the clinical course brain atrophy is not always associated with high EDSS scores. Recently much attention has been given to focal atrophy at different stages of MS [2, 5, 13, 14]. Apart from direct cell damage, the mechanism of inflammation can exert a protective effect. The immune cells recruited to the inflammatory foci produce growth factors, are able to delete myelin-associated molecules, and can have a suppressive phenotype. Therefore there are still some controversies in the inflammatory concept to be resolved.
Patients with MS receive treatment with Copaxone, Betaseron, Rebif-44, monoclonal antibodies, and cytostatics. In MS cases the most promising seems to be a complex therapy aimed at inflammatory process suppression and neuroprotection [6, 8].
The aim of our study was to investigate the role of autologous HSCT in treatment of patients with MS as a complex treatment.
The first autologous hematopoietic stem cell transplantation (auto-HSCT) was performed in 2001. According to protocol, the patients were divided into two groups based on the rate of disease progression. The patients with fast progression of MS belong to the first group. In this group we consider a salvage high-dose chemotherapy with fludarabine-melphalan conditioning regimen and auto-HSCT. The patients with a stable disease course were included into the second group and received BEAM as a conditioning regimen.
Inclusion criteria
• Definitive MS (McDonald, 2005)
• Relapsing-remitting MS; second progressive MS and aggressive MS with severe relapses.
• Age 18–55 yrs.
• Duration of MS ≥1 year
• EDSS 0–6.5
• MRI within the 30 days period before auto-SCT
• Standard therapy methods proven to be ineffective
• The increase of EDSS 1.5 (EDSS 3.0–5.0) or 1 (EDSS ≥5.5)
• 2 relapses in the last 24 months or 1 relapse in the last 12 months on standard therapy.
The follow-up period varied from 2 months to 8 years.
• Median age 34.5 (22–52) yrs
• Sex distribution: male: 11 patients, median age 31.7 (22– 41) yrs; female: 12 patients, median age 37 (26–52) yrs
• PPMS = 5 patients, SPMS = 12 patients, R-RMS = 6 patients
• Median period from debut of MS to auto-SCT: 6.8 yrs
• Median EDSS: 5.7 (1.5–7.5)ВЕАМ: 17 patients, Flu-Mel: 6 patients
• Median of neutropenia duration: 12.7 days (ВЕАМ: 12.6, Flu-Mel: 12.8 days).
To evaluate the therapy effects, clinical scales and immunological and radiological methods were used. We used the EDSS scale, MSFC clinical outcome measure, and a relapse evaluation test. The methods of immunological status evaluation included:
• detection of oligoclonal bands (OCB) in plasma and cerebrospinal fluid (CSF)
• light chain detection in plasma and CSF
• plasma and CSF T cell cytofluorometry (CD 3+CD19-; CD3+CD8+; CD3+CD4+; CD3+CD19+; CD3-CD19+; CD3-СD20+; CD3-CD(16+56); CD3+CD(16+56); CD3+HLA-DR+; CD3-HLA-DR+; CD3+HLA-DR-; CD4+CD25+; СВ19+СВ27+ phenotypes).
For CSN visualization the following MRI protocol was used:
• Routine protocol with contrast (Gd)
• T2 and T1 volume
• T1 and T2 lesion calculation
• Brain volume evaluation
Prior to auto-HSCT the patients received the following treatment: pulse therapy with steroids: 90%, beta-IFN: (Betaseron, Rebif, Avonex) 54%, mitoxantrone: 15%, Copaxone: 22%, intravenous IgG: 5%, no previous treatment: 5%.
Outcomes
Clinical symptoms evaluation: two end-points for EDSS assessment were established (day 0 and 12 months after auto-SCT). An evident therapy effect was observed in three patients, with decreases of EDSS scores from 6.5 to 1.5 in one patient, and from 5.5 to 4.5 in two patients. 10 patients (43.4%) remained with stable EDSS score values for 12 months after auto-SCT. 4 patients (17.3%) experienced disease progression (increase of EDSS). One patient died of sepsis.
MRI metrics examined included the number of Gd enhancing lesions, number of T2 lesions, total T2 lesion volume, and atrophy evaluation (decrease of total brain volume; changes in the third ventricle diameter; atrophy of corpus callosum). In the 18-month period after auto-SCT an increase in T2 lesion volumes was observed in 8% of cases, 20.4% of patients developed new T2 lesions, and 12% of patients had T1 contrast lesions. MRI signs of general brain atrophy were found in 95.6% of patients. We observed a certain discrepancy of MRI signs: while the volume of T2 lesions decreased and no signs of systemic inflammation were observed, the atrophic changes continued to progress. Judging by MRI metrics, auto-SCT can eliminate the inflammatory, but not the neurodegenerative component of MS.
Immunology: We performed cytofluorometry of serum and CSF immunocompetent cell populations, and evaluated the level of intrathecal IgG as a highly specific marker of MS. Cell population changes showed no definite pattern and are hard to interpret. No evident dynamics of intrathecal IgG level was observed.
After ASCT 91.1% patients had constant intratecal synthesis of OCB. Only in 1 patient we revealed no signs of OCB synthesis in CSF and plasma.
Early post-transplant period complications: infectious complications: 84%; hemorrhagic complications: 54%; serum sickness: 44%; neurological complications: 30%.
Conclusions
Our results show the evident decrease of inflammatory changes and better disease control in MS patients treated with conventional chemotherapy or high-dose chemotherapy with auto-HSCT due to its immunosuppressive effect. However, more intensive therapy is associated with a higher complications rate and risk of mortality. There are some questions still unanswered. It is still to be determined whether the conventional regimens able to roll the disease course back to previous stages or more radical high-dose therapy lead to better long-term survival and disease control. Also still to be determined is the best time for high-dose therapeutic intervention.
On the whole, auto-HSCT is a promising method of MS treatment, but there are certain practical aspects to be developed:
• Indications for auto-SCT
• Conditioning regimen
• Stem cell source and transplant processing
• Complex methods of disease course evaluation (clinical, immunological, radiological, and morphological evaluation)
• Quality of life evaluation
• Role of mesenchymal stem cells and monoclonal antibodies in the treatment of multiple sclerosis.
References
1. Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol. 2004;55:458-68. doi: 10.1002/ana.20016.
2. Benedict RH, Hussein S, Englert J, Dwyer MG, Abdelrahman N, Cox JL, et al. Cortical atrophy and personality in multiple sclerosis. Neuropsychology. 2008;22:432-41. doi: 10.1037/0894-4105.22.4.432.
3. Evdoshenko E, Maslyansky A, Zaslavsky L, Skoromets A, Ziuzgin I, Riabykina O, et al. Opportunities of anti B-cell therapy in multiple sclerosis. Medical Immunology. 2009;11:63-70.
5. Giorgio A, Battaglini M, Smith SM, De Stefano N. Brain atrophy assessment in multiple sclerosis: importance and limitations. Neuroimaging Clin N Am. 2008;18:675-86, xi. doi: 10.1016/j.nic.2008.06.007.
6. Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H. The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J Neuroimmunol. 2000;107:161-6.
8. Kerschensteiner M, Hohlfeld R. Neurotrophic factors protect myelin from attack. Int MS J. 2003;10:2-4.
9. Lucchinetti CF, Parisi J, Bruck W. The pathology of multiple sclerosis. Neurol Clin. 2005;23:77-105,vi. doi: 10.1016/j.ncl.2004.09.002.
10. Montalban X, Sastre-Garriga J, Filippi M, Khaleeli Z, Tellez N, Vellinga MM, et al. Primary progressive multiple sclerosis diagnostic criteria: a reappraisal. Mult Scler. 2009;15:1459-65.
11. Morales Y, Parisi JE, Lucchinetti CF. The pathology of multiple sclerosis: evidence for heterogeneity. Adv Neurol. 2006;98:27-45.
12. Prakhova LN, Il'ves AG, Petrov AM, Kataeva GV, Pozdniakov AV, Totolian NA, et al. [Brain atrophy and neurological impairment in patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109:32-7.
15. Sanchez MP, Nieto A, Barroso J, Martin V, Hernandez MA. Brain atrophy as a marker of cognitive impairment in mildly disabling relapsing-remitting multiple sclerosis. Eur J Neurol. 2008;15:1091-9. doi: 10.1111/j.1468-1331.2008.02259.x.
" ["~DETAIL_TEXT"]=> string(13592) "Introduction
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, producing multifocal neurological symptoms caused by nerve demyelination and progressive neurodegeneration. The pathological hallmark of MS is multiple demyelinated plaques (sharply defined areas of demyelination) in the white matter and widely distributed areas of degeneration [7, 10]. The core process in MS is inflammatory, with T cells and their mediators triggering myelin injury; additionally, oligodendrocyte/myelin damage is often mediated by autoantibody fixation with consequent complement activation. Therefore, multiple sclerosis is an autoimmune condition with a complex pathogenesis involving cellular and humoral immune response activation [3].
Presently in MS four types of neural tissue injury can be distinguished [9]. Two of them are caused by activation of cellular and humoral immune system compartments, and the others are characterized by degenerative changes in oligodendrocytes with primary or distal injury. These four types can occur at the different stages of MS. The present conception of MS pathogenesis encompasses two basic mechanisms – autoimmune inflammation and neurodegenerative changes [1, 11].
Multiple studies and clinical observations showed the progressive decrease of brain tissue total volume in MS [4, 12, 15, 16]. The beginning of the disease course is characterized by repeated episodes of inflammation with new contrast-accumulating T2 lesions revealed by MRI. However a considerable amount of recent data suggests the importance of degenerative changes at the earliest stages of the disease [4]. Today the pathogenesis of MS is considered to be a complex process with the inflammatory component being only a part of the general process.
Even small T2 lesions can be associated with general atrophy, though within the clinical course brain atrophy is not always associated with high EDSS scores. Recently much attention has been given to focal atrophy at different stages of MS [2, 5, 13, 14]. Apart from direct cell damage, the mechanism of inflammation can exert a protective effect. The immune cells recruited to the inflammatory foci produce growth factors, are able to delete myelin-associated molecules, and can have a suppressive phenotype. Therefore there are still some controversies in the inflammatory concept to be resolved.
Patients with MS receive treatment with Copaxone, Betaseron, Rebif-44, monoclonal antibodies, and cytostatics. In MS cases the most promising seems to be a complex therapy aimed at inflammatory process suppression and neuroprotection [6, 8].
The aim of our study was to investigate the role of autologous HSCT in treatment of patients with MS as a complex treatment.
The first autologous hematopoietic stem cell transplantation (auto-HSCT) was performed in 2001. According to protocol, the patients were divided into two groups based on the rate of disease progression. The patients with fast progression of MS belong to the first group. In this group we consider a salvage high-dose chemotherapy with fludarabine-melphalan conditioning regimen and auto-HSCT. The patients with a stable disease course were included into the second group and received BEAM as a conditioning regimen.
Inclusion criteria
• Definitive MS (McDonald, 2005)
• Relapsing-remitting MS; second progressive MS and aggressive MS with severe relapses.
• Age 18–55 yrs.
• Duration of MS ≥1 year
• EDSS 0–6.5
• MRI within the 30 days period before auto-SCT
• Standard therapy methods proven to be ineffective
• The increase of EDSS 1.5 (EDSS 3.0–5.0) or 1 (EDSS ≥5.5)
• 2 relapses in the last 24 months or 1 relapse in the last 12 months on standard therapy.
The follow-up period varied from 2 months to 8 years.
• Median age 34.5 (22–52) yrs
• Sex distribution: male: 11 patients, median age 31.7 (22– 41) yrs; female: 12 patients, median age 37 (26–52) yrs
• PPMS = 5 patients, SPMS = 12 patients, R-RMS = 6 patients
• Median period from debut of MS to auto-SCT: 6.8 yrs
• Median EDSS: 5.7 (1.5–7.5)ВЕАМ: 17 patients, Flu-Mel: 6 patients
• Median of neutropenia duration: 12.7 days (ВЕАМ: 12.6, Flu-Mel: 12.8 days).
To evaluate the therapy effects, clinical scales and immunological and radiological methods were used. We used the EDSS scale, MSFC clinical outcome measure, and a relapse evaluation test. The methods of immunological status evaluation included:
• detection of oligoclonal bands (OCB) in plasma and cerebrospinal fluid (CSF)
• light chain detection in plasma and CSF
• plasma and CSF T cell cytofluorometry (CD 3+CD19-; CD3+CD8+; CD3+CD4+; CD3+CD19+; CD3-CD19+; CD3-СD20+; CD3-CD(16+56); CD3+CD(16+56); CD3+HLA-DR+; CD3-HLA-DR+; CD3+HLA-DR-; CD4+CD25+; СВ19+СВ27+ phenotypes).
For CSN visualization the following MRI protocol was used:
• Routine protocol with contrast (Gd)
• T2 and T1 volume
• T1 and T2 lesion calculation
• Brain volume evaluation
Prior to auto-HSCT the patients received the following treatment: pulse therapy with steroids: 90%, beta-IFN: (Betaseron, Rebif, Avonex) 54%, mitoxantrone: 15%, Copaxone: 22%, intravenous IgG: 5%, no previous treatment: 5%.
Outcomes
Clinical symptoms evaluation: two end-points for EDSS assessment were established (day 0 and 12 months after auto-SCT). An evident therapy effect was observed in three patients, with decreases of EDSS scores from 6.5 to 1.5 in one patient, and from 5.5 to 4.5 in two patients. 10 patients (43.4%) remained with stable EDSS score values for 12 months after auto-SCT. 4 patients (17.3%) experienced disease progression (increase of EDSS). One patient died of sepsis.
MRI metrics examined included the number of Gd enhancing lesions, number of T2 lesions, total T2 lesion volume, and atrophy evaluation (decrease of total brain volume; changes in the third ventricle diameter; atrophy of corpus callosum). In the 18-month period after auto-SCT an increase in T2 lesion volumes was observed in 8% of cases, 20.4% of patients developed new T2 lesions, and 12% of patients had T1 contrast lesions. MRI signs of general brain atrophy were found in 95.6% of patients. We observed a certain discrepancy of MRI signs: while the volume of T2 lesions decreased and no signs of systemic inflammation were observed, the atrophic changes continued to progress. Judging by MRI metrics, auto-SCT can eliminate the inflammatory, but not the neurodegenerative component of MS.
Immunology: We performed cytofluorometry of serum and CSF immunocompetent cell populations, and evaluated the level of intrathecal IgG as a highly specific marker of MS. Cell population changes showed no definite pattern and are hard to interpret. No evident dynamics of intrathecal IgG level was observed.
After ASCT 91.1% patients had constant intratecal synthesis of OCB. Only in 1 patient we revealed no signs of OCB synthesis in CSF and plasma.
Early post-transplant period complications: infectious complications: 84%; hemorrhagic complications: 54%; serum sickness: 44%; neurological complications: 30%.
Conclusions
Our results show the evident decrease of inflammatory changes and better disease control in MS patients treated with conventional chemotherapy or high-dose chemotherapy with auto-HSCT due to its immunosuppressive effect. However, more intensive therapy is associated with a higher complications rate and risk of mortality. There are some questions still unanswered. It is still to be determined whether the conventional regimens able to roll the disease course back to previous stages or more radical high-dose therapy lead to better long-term survival and disease control. Also still to be determined is the best time for high-dose therapeutic intervention.
On the whole, auto-HSCT is a promising method of MS treatment, but there are certain practical aspects to be developed:
• Indications for auto-SCT
• Conditioning regimen
• Stem cell source and transplant processing
• Complex methods of disease course evaluation (clinical, immunological, radiological, and morphological evaluation)
• Quality of life evaluation
• Role of mesenchymal stem cells and monoclonal antibodies in the treatment of multiple sclerosis.
References
1. Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol. 2004;55:458-68. doi: 10.1002/ana.20016.
2. Benedict RH, Hussein S, Englert J, Dwyer MG, Abdelrahman N, Cox JL, et al. Cortical atrophy and personality in multiple sclerosis. Neuropsychology. 2008;22:432-41. doi: 10.1037/0894-4105.22.4.432.
3. Evdoshenko E, Maslyansky A, Zaslavsky L, Skoromets A, Ziuzgin I, Riabykina O, et al. Opportunities of anti B-cell therapy in multiple sclerosis. Medical Immunology. 2009;11:63-70.
5. Giorgio A, Battaglini M, Smith SM, De Stefano N. Brain atrophy assessment in multiple sclerosis: importance and limitations. Neuroimaging Clin N Am. 2008;18:675-86, xi. doi: 10.1016/j.nic.2008.06.007.
6. Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H. The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J Neuroimmunol. 2000;107:161-6.
8. Kerschensteiner M, Hohlfeld R. Neurotrophic factors protect myelin from attack. Int MS J. 2003;10:2-4.
9. Lucchinetti CF, Parisi J, Bruck W. The pathology of multiple sclerosis. Neurol Clin. 2005;23:77-105,vi. doi: 10.1016/j.ncl.2004.09.002.
10. Montalban X, Sastre-Garriga J, Filippi M, Khaleeli Z, Tellez N, Vellinga MM, et al. Primary progressive multiple sclerosis diagnostic criteria: a reappraisal. Mult Scler. 2009;15:1459-65.
11. Morales Y, Parisi JE, Lucchinetti CF. The pathology of multiple sclerosis: evidence for heterogeneity. Adv Neurol. 2006;98:27-45.
12. Prakhova LN, Il'ves AG, Petrov AM, Kataeva GV, Pozdniakov AV, Totolian NA, et al. [Brain atrophy and neurological impairment in patients with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109:32-7.
15. Sanchez MP, Nieto A, Barroso J, Martin V, Hernandez MA. Brain atrophy as a marker of cognitive impairment in mildly disabling relapsing-remitting multiple sclerosis. Eur J Neurol. 2008;15:1091-9. doi: 10.1111/j.1468-1331.2008.02259.x.
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Евдошенко, Людмила Ст. Зубаровская, Леонид Г. Заславский, Александр А. Скоромец, Сергей М. Алексеев, Юлия А. Станкевич, Наталья А. Тотолян, Борис В. Афанасьев</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(307) "Евгений П. Евдошенко, Людмила Ст. Зубаровская, Леонид Г. Заславский, Александр А. Скоромец, Сергей М. Алексеев, Юлия А. Станкевич, Наталья А. Тотолян, Борис В. Афанасьев
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18391" ["VALUE"]=> array(2) { ["TEXT"]=> string(1125) "<p class="bodytext">В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев. </p> <h3>Ключевые слова</h3> <p> аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1079) "В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев.
Ключевые слова
аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз
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" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18414" ["VALUE"]=> array(2) { ["TEXT"]=> string(558) "<p class="bodytext">The results of observing 23 patients with multiple sclerosis who received autologous hematopoietic stem cell transplantation are shown in this article. The risks of an auto-HSCT and its advantages compared with other therapy methods, and also an optimal choice for the therapy predictors are discussed. The results show progress of disease in most cases after 12-18 months. </p> <h3>Keywords </h3> <p>autologous hematopoietic stem cell transplantation (auto-HSCT), multiple sclerosis </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(512) "The results of observing 23 patients with multiple sclerosis who received autologous hematopoietic stem cell transplantation are shown in this article. The risks of an auto-HSCT and its advantages compared with other therapy methods, and also an optimal choice for the therapy predictors are discussed. The results show progress of disease in most cases after 12-18 months.
Keywords
autologous hematopoietic stem cell transplantation (auto-HSCT), multiple sclerosis
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autologous hematopoietic stem cell transplantation (auto-HSCT), multiple sclerosis
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autologous hematopoietic stem cell transplantation (auto-HSCT), multiple sclerosis
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Gorbacheva Institute of Children Hematology and Transplantation, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia; <sup>3</sup>Chair of Neurology, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia; <sup>4</sup>BMT Unit for adults, Memorial R.M. Gorbacheva Institute of Children Hematology and Transplantation, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(688) "1Leningrad Region Center for Multiple Sclerosis, Leningrad Region Clinical Hospital/ Chair of Neurology, Department of Neurology, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia; 2Memorial R.M. 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Evdoshenko" ["LINK_ELEMENT_VALUE"]=> bool(false) } ["SUMMARY_RU"]=> array(37) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18391" ["VALUE"]=> array(2) { ["TEXT"]=> string(1125) "<p class="bodytext">В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев. </p> <h3>Ключевые слова</h3> <p> аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1079) "В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев.
Ключевые слова
аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(1079) "В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев.
Ключевые слова
аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз
" } } } [7]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "76" ["~IBLOCK_SECTION_ID"]=> string(2) "76" ["ID"]=> string(4) "1375" ["~ID"]=> string(4) "1375" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["~NAME"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(19) "22.09.2017 15:50:39" ["~TIMESTAMP_X"]=> string(19) "22.09.2017 15:50:39" ["DETAIL_PAGE_URL"]=> string(135) "/ru/archive/tom-2-nomer-2-6/stati/otsenki-dannye-patsientami-s-rasseyannym-sklerozom-posle-autologichnoy-transplantatsii-stvolovykh-kr/" ["~DETAIL_PAGE_URL"]=> string(135) "/ru/archive/tom-2-nomer-2-6/stati/otsenki-dannye-patsientami-s-rasseyannym-sklerozom-posle-autologichnoy-transplantatsii-stvolovykh-kr/" ["LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["~LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["DETAIL_TEXT"]=> string(25359) "Introduction
Multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system (CNS), associated with a broad spectrum of physical, psychological, and social impairments. MS patients suffer from a variety of symptoms such as fatigue, spasticity, problems with balance and coordination, visual impairment, bowel or bladder dysfunction, decreased cognitive function, etc., and these symptoms decrease their quality of life (QoL) [6, 11]. Most importantly, the level of impact of the wide range of health problems associated with MS needs to be understood in terms of patients’ own perceptions of those impacts and the degree to which they affect their lives [9, 4].
Currently there is no known cure for MS. Thus, the goal of treatment is to control symptoms and improve a patient’s quality of life. In order to evaluate the efficacy of treatment or rehabilitation of MS patients it is necessary to assess patients’ QoL and severity of symptoms [5, 10]. “Quality of life of a patient” is a new and important category in clinical medicine. To assess it in a proper way it is worthwhile to define it clearly.
There are many definitions of QoL at present. The one which is most relevant to clinical setting is as follows: “Quality of life is integral characteristics of a physical, psychological, and social functioning of an individual, based on his/her subjective perception” (A. Novik, T. Ionova, P. Kind, 1999).
This definition covers 3 major domains of an individual’s function:
(1) Physical well-being;
(2) Psychological well-being;
(3) Social well-being.
Importantly it implies self-assessment. Special tools have been developed to measure QOL and symptoms. QoL questionnaires and symptom assessment tools refer to patient-reported outcomes (PRO) [2, 1]. PRO is an umbrella term that is widely used at present. It covers a whole range of potential types of measurement, but is used specifically to refer to questionnaires completed by the patient. The most commonly used PRO measures assess QoL and symptoms.
There are several QoL measures which are used for evaluating QOL in MS. The most widespread are general QoL questionnaires: RAND Short Form-36 (SF-36), EQ-5D, and Sickness Impact Profile (SIP). MS-specific measures of QOL include the Functional Assessment of Multiple Sclerosis (FAMS), the Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54), and the Disability & Impact Profile (DIP).
As for symptom assessment tools it is worth mentioning the Comprehensive Symptom Profile-MS-22 Short Form (CSP-MS-22-SF). This instrument was developed in 2007 by the New Jersey Center for Quality of Life and Health Outcome Research (USA) and Multinational Center for QoL Research (Russia) [3]. The CSP-MS-22-SF aims to assess the severity of 22 symptoms that are common and most disturbing for MS patients. It consists of numerical analogous scales, scored from “0” (no symptom) to “10” (most expressed symptom). Applicability of CSP-MS-22-SF with the analysis of its psychometric properties was tested in the study which included more than 120 patients with different types of MS.
At present high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (ASCT) has been used with increasing frequency as a therapeutic option for MS patients. Both disease-free period and improvement of the patient’s quality of life (QoL) are recognized as important outcome parameters. With this in mind, evaluation of both clinical and patient-reported outcomes in MS patients after ASCT is worthwhile. A comprehensive analysis of PRO has not been available. Thus, we aimed to study PRO in MS patients after ASCT.
Patients and methods
101 patients with MS (secondary progressive: 41 patients, primary progressive: 21, progressive-relapsing: 5 and relapsing-remitting: 34) were included in this study (mean age 32.5, range: 17–54; male/female 42/59). BEAM or BEAM-modified conditioning was used. Median EDSS at baseline was 5.0 (range 1.5–8.5). The mean follow-up duration was 21 months (range 6–120 months).
QoL was assessed using RAND SF-36 and FAMS. RAND SF-36 is a general QoL measure which consists of 36 questions and contains 8 scales: physical functioning, role–physical functioning, bodily pain, general health, vitality, social functioning, role–emotional functioning, and mental health. The FAMS is disease specific to assess QoL in MS patients. It consists of 58 questions and contains 7 scales: mobility, symptoms, emotional well-being, general contentment, thinking and fatigue, family/social well-being, additional concerns. Symptom severity was assessed using CSP-MS-22-SF. Patients filled in the questionnaires at baseline, at discharge, at 3, 6, 9, and 12 months, and every 6 months thereafter.
QoL treatment response was classified as improvement, stabilization, or worsening. To determine QoL treatment response the Integral QoL Index (IQLI) was calculated for each patient using the method of Integral Profiles on the basis of SF-36 scales (A. Novik, T. Ionova, A. Kishtovich, 2005) [8].
Using IQLI the grade of QoL impairment was determined for each patient. According to the grades of QoL impairment, five groups of patients can be identified: with no QoL impairment, mild QoL impairment, moderate QoL impairment, severe QoL impairment, and critical QoL impairment [7].
No QoL impairment means that a patient has no QoL decrease from a population norm (PN), mild QoL impairment <25% decrease from a PN, moderate QoL impairment 25–50% decrease from a PN, severe QoL impairment 50–75% decrease from a PN, and critical QoL impairment >75% decrease from a PN.
Results
Quality of life parameters in MS patients after ASCT
Monitoring of QoL parameters using the MS specific QoL questionnaire FAMS was made. QoL parameters at discharge, 6 months post-transplant, and 12 months post-transplant as compared to base-line are presented on Fig. 1–3. As can be seen from the figures, quality of life parameters are lower at the baseline than after ASCT across the majority of FAMS scales. Statistically significant improvement at baseline was found for the following scales: emotional well-being (p<0.001), general contentment (p<0.05), family/social well-being (p<0.001), and additional concerns (p<0.001).
In 6 months after ASCT statistically significant improvement as compared to base-line was registered across all scales except family/social well-being and additional concerns: mobility (p<0.001), symptoms (p<0.001), emotional well-being (p<0.01), general contentment (p<0.01), thinking and fatigue (p<0.01), and additional concerns (p<0.001). In a year the post-transplant QoL parameters had further increased with statistically significant improvement across all scales (p<0.01) except family/social well-being.
Mean total FAMS score at base-line was 115.5 (SD 29.6). At discharge it improved to 121.1 (SD 29.8; p<0.05) with further improvement in 6 months (mean 130.6; SD 31.8; p<0.01), and in a year post-transplant (mean 134.8; SD 28.1; p<0.001).
Figure 1. Quality of life parameters of MS patients before ASCT and at discharge (FAMS questionnaire)
Figure 2. Quality of life parameters of MS patients before ASCT and 6 months after ASCT (FAMS questionnaire)
Figure 3. Quality of life parameters of MS patients before ASCT and 12 months after ASCT (FAMS questionnaire)
Further analysis included the comparison of QoL parameters of MS patients before and after ASCT as compared with the population norm. For these purposes QoL was measured using RAND SF-36. Quality of life profiles of MS patients at baseline and 6 months post-transplant as well as of the population norm are presented in Fig. 4. As can be seen, the quality of life profile in MS patients before ASCT is characterized by compression and deformation as compared with the population norm. Quality of life parameters of MS patients before ASCT were significantly lower than of the population norm across all SF-36 scales. Six months after transplantation definite improvement of QoL parameters was registered, with statistically significant changes across all the scales (p<0.01) except pain and role–emotional functioning. The Mean Integral QoL Index increased dramatically as compared to base-line value (0.32 (SD 0.26) vs. 0.50 (SD 0.28); p< 0.01).
Figure 4. Quality of life profiles in MS patients before and 6 months after ASCT as compared with the population norm (SF-36 questionnaire)
Note: PF = physical functioning, RPF = role–physical functioning, BP = bodily pain, GH = general health, V = vitality, SF = social functioning, REF = role–emotional functioning, MH = mental health.
Taking into account the patients’ heterogeneity in terms of their QoL the patients were stratified at baseline by the grades of QoL impairment. Five groups were identified according to the grades of QoL impairment: with no QoL impairment, mild QoL impairment, moderate QoL impairment, severe QoL impairment, and critical QoL impairment.
Distribution of patients according to the grades of QoL impairment before and 6 months after ASCT is shown in Table 1.
Table 1. Distribution of patients according to the grades of QoL impairment before ASCT and 6 months post-transplant (n=33)
|
QoL impairment grade |
N, % |
|
|---|---|---|
|
Before ASCT |
After ASCT |
|
|
No QoL impairment |
9 (27) |
17 (52) |
|
Mild QoL impairment |
4 (13) |
3 (9) |
|
Moderate QoL impairment |
1 (3) |
4 (13) |
|
Severe QoL impairment |
10 (30) |
7 (20) |
|
Critical QoL impairment |
9 (27) |
2 (6 |
Changes in the distribution of patients according to the grades of QoL impairment took place after ASCT. The number of patients with no QoL impairment increased after transplantation, while the number of patients with critical QoL impairment decreased. Notably, ASCT resulted in a two-fold increase in the number of patients with QoL comparable to population norms: before transplantation 27% of patients had no QoL impairment, and 6 months after ASCT it was 52%. At the same time the number of patients with critical QoL impairment had experienced a triple decrease: at base-line 27% of patients had critical QoL impairment, and 6 months after ASCT it was only 6%.
Thus, ASCT is accompanied by an increase in the number of patients with no QoL impairment and a decrease in the number of patients with critical QoL impairment.
Symptoms in MS patients after ASCT
Symptom prevalence in MS patients before and after ASCT is presented in Fig. 5. Before transplantation MS patients experienced a wide range of symptoms. The most prevalent symptom was fatigue (83%). Of those who had fatigue about half of the patients reported it at moderate-to-severe level. The other frequent symptoms were toddling, heat sensitivity, psychological problems (anxiety and sadness) and numbness/tingling with their prevalence of 79%, 76%, 72%, and 70%, respectively. More than half of the patients reported these symptoms at the moderate-to-severe level. The majority of patients (60% on average) experienced such symptoms as movement disorders, coordination problems, urination dysfunction, and vision impairment.
In response to treatment, changes in symptom prevalence in MS patients were found. Positive changes in prevalence of the most frequent symptoms – fatigue, toddling, psychological problems (anxiety and sadness), numbness/tingling, movement disorders, coordination problems, urination dysfunction, and vision impairment – were observed 6 months after ASCT. The prevalence of the vast majority of moderate-to-severe symptoms after transplantation was lower than before treatment.
Figure 5. Symptom prevalence in MS patients before ASCT and 6 months post-transplant
Information about symptom severity in MS patients before and 6 months after ASCT is presented in Table 2. Before transplantation the most severe symptom was toddling followed by heat sensitivity, fatigue, movement disorders, and coordination disorders. In response to treatment, the severity of these symptoms decreased. As it is seen from the table the mean value of the severity of these symptoms 6 months after ASCT was lower than before treatment. The severity of other symptoms decreased as well.
Table 2. Symptom severity in MS patients before ASCT and 6 months post-transplant
|
Symptoms |
Before ASCT |
6 months after ASCT |
|---|---|---|
|
Mean (SD) |
Meand (SD) |
|
|
Toddling |
5.3(4.1) |
4.2(4.0) |
|
Heat sensitivity |
4.7(3.7) |
4.5(3.8) |
|
Fatigue |
4.4(3.1) |
3.5(3.0) |
|
Movement disorders |
3.9(3.8) |
3.2(3.8) |
|
Coordination disorders |
3.7(3.8) |
3.0(3.8) |
|
Urination dysfunction |
3.3(3.8) |
1.9(2.8) |
|
Numbness/tingling |
3.3(3.3) |
1.8(2.4) |
|
Stool problems |
3.2(3.6) |
2.4(3.4) |
|
Anxiety |
3.0(2.9) |
1.8(2.7) |
|
Vision impairment |
2.8(3.4) |
1.9(3.1) |
|
Sadness |
2.8(3.0) |
1.6(2.7) |
|
Dizziness |
2.3(2.9) |
1.2(2.0) |
|
Muscle cramps |
2.1(3.0) |
2.0(3.0) |
|
Sexual dysfunction |
2.0(3.7) |
1.4(2.9) |
|
Pain |
1.5(2.2) |
1.2(2.1) |
|
Decreased concentration |
1.3(1.9) |
1.4(2.5) |
|
Memory loss |
1.1(2.0) |
1.2(2.3) |
|
Tremor |
1.1(1.9) |
0.9(2.0) |
|
Chills |
0.8(1.9) |
1.3(2.7) |
|
Speech disorders |
0.7(1.9) |
0.9(1.8) |
|
Hearing disorders |
0.5(1.7) |
0.4(1.6) |
|
Swallowing problems |
0.4(0.8) |
0.3(1.1) |
QoL treatment response in MS patients after ASCT
QoL treatment response characterizes changes in physical, psychological, and social functioning of a patient after treatment. Three types of QoL treatment response after ASCT can be identified: improvement, stabilization, and worsening.
QoL treatment response was determined at different time-points after ASCT. Here we present the data on QoL treatment response at 6 months post-transplant (n=33). Three types of QoL treatment response were registered: improvement, stabilization, or worsening. QoL improvement or QoL stabilization was shown in the vast majority of patients. QoL improvement was achieved in 16 (48.5%) patients; and QoL stabilization in other 16 patients. QoL worsening was noticed in one patient only.
Thus, the vast majority of patients (97%) experienced either QoL improvement or QoL stabilization in 6 months after ASCT.
Conclusions
1. Physical, psychological and social functioning in MS patients is significantly deteriorated. The quality of life profile of these patients is characterized by compression and deformation. The majority of patients exhibit either severe or critical QoL impairment.
2. MS patients experience a wide range of disease-related symptoms. The most frequent symptoms – fatigue, toddling, heat sensitivity, psychological problems (anxiety and sadness), and numbness/tingling – are present in more than 70% of patients. About a half of the patients report these symptoms at the moderate-to-severe level.
3. ASCT in MS patients improves their physical, psychological and social function. The most definite improvement of quality of life takes place in a year after transplantation.
4. After ASCT the number of patients with no QoL impairment increases whereas the number of patients with critical QoL impairment decreases.
5. Quality of life treatment response (QoL improvement or QoL stabilization) was achieved in the vast majority of MS patients after ASCT.
6. ASCT is associated with decline of symptom prevalence and severity in MS patients.
References
2. FDA Guidance for Industry: Patient-reported outcome measures: use in medical product development to support labeling claims. Bulletin of the Multinational Center of Quality of Life Research. 2006;7-8:153-154.
3. Fedorenko DA, Kishtovich AV, Ionova TI, Novik АА. Symptom assessment in patients with multiple sclerosis after hematopoietic stem cell transplantation. Bulletin of the Multinational Center of Quality of Life Research. 2008;11-12:157-158.
5. Nortvedt MW, Riise T, Myhr KM, et al. Quality of life as a predictor for change in disability in MS. Neurology. 2000 Jul 12;55(1):51-4.
6. Nortvedt MW, Riise T, Myhr KM, et al. Quality of life in multiple sclerosis: measuring the disease effects more broadly. // Neurology. 1999;22(53):1098-1103.
7. Novik AA, Ionova TI. Guidelines of quality of life research in medicine. М: Olma Media Grupp, 2007.
8. Novik AA, Ionova TI, Kalyadina SA, Kishtovich AV. Conceptual and statistical models of stratification of the patients population according to the grades of quality of life impairement. Bulletin of the Multinational Center of Quality of Life Research. 2007;9-10:88-98.
10. Rice GP, Oger J, Duquette P, et al. Treatment with interferon beta-1b improves quality of life in multiple sclerosis. // Can. J. Neurol. Sci. 1999;26(4):276-282.
11. The Canadian Burden of Illness Study Group. Burden of illness of multiple sclerosis: Part II: Quality of life. // Can. J. Neurol. Sci. 1998;25:31-38.
" ["~DETAIL_TEXT"]=> string(25359) "Introduction
Multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system (CNS), associated with a broad spectrum of physical, psychological, and social impairments. MS patients suffer from a variety of symptoms such as fatigue, spasticity, problems with balance and coordination, visual impairment, bowel or bladder dysfunction, decreased cognitive function, etc., and these symptoms decrease their quality of life (QoL) [6, 11]. Most importantly, the level of impact of the wide range of health problems associated with MS needs to be understood in terms of patients’ own perceptions of those impacts and the degree to which they affect their lives [9, 4].
Currently there is no known cure for MS. Thus, the goal of treatment is to control symptoms and improve a patient’s quality of life. In order to evaluate the efficacy of treatment or rehabilitation of MS patients it is necessary to assess patients’ QoL and severity of symptoms [5, 10]. “Quality of life of a patient” is a new and important category in clinical medicine. To assess it in a proper way it is worthwhile to define it clearly.
There are many definitions of QoL at present. The one which is most relevant to clinical setting is as follows: “Quality of life is integral characteristics of a physical, psychological, and social functioning of an individual, based on his/her subjective perception” (A. Novik, T. Ionova, P. Kind, 1999).
This definition covers 3 major domains of an individual’s function:
(1) Physical well-being;
(2) Psychological well-being;
(3) Social well-being.
Importantly it implies self-assessment. Special tools have been developed to measure QOL and symptoms. QoL questionnaires and symptom assessment tools refer to patient-reported outcomes (PRO) [2, 1]. PRO is an umbrella term that is widely used at present. It covers a whole range of potential types of measurement, but is used specifically to refer to questionnaires completed by the patient. The most commonly used PRO measures assess QoL and symptoms.
There are several QoL measures which are used for evaluating QOL in MS. The most widespread are general QoL questionnaires: RAND Short Form-36 (SF-36), EQ-5D, and Sickness Impact Profile (SIP). MS-specific measures of QOL include the Functional Assessment of Multiple Sclerosis (FAMS), the Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54), and the Disability & Impact Profile (DIP).
As for symptom assessment tools it is worth mentioning the Comprehensive Symptom Profile-MS-22 Short Form (CSP-MS-22-SF). This instrument was developed in 2007 by the New Jersey Center for Quality of Life and Health Outcome Research (USA) and Multinational Center for QoL Research (Russia) [3]. The CSP-MS-22-SF aims to assess the severity of 22 symptoms that are common and most disturbing for MS patients. It consists of numerical analogous scales, scored from “0” (no symptom) to “10” (most expressed symptom). Applicability of CSP-MS-22-SF with the analysis of its psychometric properties was tested in the study which included more than 120 patients with different types of MS.
At present high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (ASCT) has been used with increasing frequency as a therapeutic option for MS patients. Both disease-free period and improvement of the patient’s quality of life (QoL) are recognized as important outcome parameters. With this in mind, evaluation of both clinical and patient-reported outcomes in MS patients after ASCT is worthwhile. A comprehensive analysis of PRO has not been available. Thus, we aimed to study PRO in MS patients after ASCT.
Patients and methods
101 patients with MS (secondary progressive: 41 patients, primary progressive: 21, progressive-relapsing: 5 and relapsing-remitting: 34) were included in this study (mean age 32.5, range: 17–54; male/female 42/59). BEAM or BEAM-modified conditioning was used. Median EDSS at baseline was 5.0 (range 1.5–8.5). The mean follow-up duration was 21 months (range 6–120 months).
QoL was assessed using RAND SF-36 and FAMS. RAND SF-36 is a general QoL measure which consists of 36 questions and contains 8 scales: physical functioning, role–physical functioning, bodily pain, general health, vitality, social functioning, role–emotional functioning, and mental health. The FAMS is disease specific to assess QoL in MS patients. It consists of 58 questions and contains 7 scales: mobility, symptoms, emotional well-being, general contentment, thinking and fatigue, family/social well-being, additional concerns. Symptom severity was assessed using CSP-MS-22-SF. Patients filled in the questionnaires at baseline, at discharge, at 3, 6, 9, and 12 months, and every 6 months thereafter.
QoL treatment response was classified as improvement, stabilization, or worsening. To determine QoL treatment response the Integral QoL Index (IQLI) was calculated for each patient using the method of Integral Profiles on the basis of SF-36 scales (A. Novik, T. Ionova, A. Kishtovich, 2005) [8].
Using IQLI the grade of QoL impairment was determined for each patient. According to the grades of QoL impairment, five groups of patients can be identified: with no QoL impairment, mild QoL impairment, moderate QoL impairment, severe QoL impairment, and critical QoL impairment [7].
No QoL impairment means that a patient has no QoL decrease from a population norm (PN), mild QoL impairment <25% decrease from a PN, moderate QoL impairment 25–50% decrease from a PN, severe QoL impairment 50–75% decrease from a PN, and critical QoL impairment >75% decrease from a PN.
Results
Quality of life parameters in MS patients after ASCT
Monitoring of QoL parameters using the MS specific QoL questionnaire FAMS was made. QoL parameters at discharge, 6 months post-transplant, and 12 months post-transplant as compared to base-line are presented on Fig. 1–3. As can be seen from the figures, quality of life parameters are lower at the baseline than after ASCT across the majority of FAMS scales. Statistically significant improvement at baseline was found for the following scales: emotional well-being (p<0.001), general contentment (p<0.05), family/social well-being (p<0.001), and additional concerns (p<0.001).
In 6 months after ASCT statistically significant improvement as compared to base-line was registered across all scales except family/social well-being and additional concerns: mobility (p<0.001), symptoms (p<0.001), emotional well-being (p<0.01), general contentment (p<0.01), thinking and fatigue (p<0.01), and additional concerns (p<0.001). In a year the post-transplant QoL parameters had further increased with statistically significant improvement across all scales (p<0.01) except family/social well-being.
Mean total FAMS score at base-line was 115.5 (SD 29.6). At discharge it improved to 121.1 (SD 29.8; p<0.05) with further improvement in 6 months (mean 130.6; SD 31.8; p<0.01), and in a year post-transplant (mean 134.8; SD 28.1; p<0.001).
Figure 1. Quality of life parameters of MS patients before ASCT and at discharge (FAMS questionnaire)
Figure 2. Quality of life parameters of MS patients before ASCT and 6 months after ASCT (FAMS questionnaire)
Figure 3. Quality of life parameters of MS patients before ASCT and 12 months after ASCT (FAMS questionnaire)
Further analysis included the comparison of QoL parameters of MS patients before and after ASCT as compared with the population norm. For these purposes QoL was measured using RAND SF-36. Quality of life profiles of MS patients at baseline and 6 months post-transplant as well as of the population norm are presented in Fig. 4. As can be seen, the quality of life profile in MS patients before ASCT is characterized by compression and deformation as compared with the population norm. Quality of life parameters of MS patients before ASCT were significantly lower than of the population norm across all SF-36 scales. Six months after transplantation definite improvement of QoL parameters was registered, with statistically significant changes across all the scales (p<0.01) except pain and role–emotional functioning. The Mean Integral QoL Index increased dramatically as compared to base-line value (0.32 (SD 0.26) vs. 0.50 (SD 0.28); p< 0.01).
Figure 4. Quality of life profiles in MS patients before and 6 months after ASCT as compared with the population norm (SF-36 questionnaire)
Note: PF = physical functioning, RPF = role–physical functioning, BP = bodily pain, GH = general health, V = vitality, SF = social functioning, REF = role–emotional functioning, MH = mental health.
Taking into account the patients’ heterogeneity in terms of their QoL the patients were stratified at baseline by the grades of QoL impairment. Five groups were identified according to the grades of QoL impairment: with no QoL impairment, mild QoL impairment, moderate QoL impairment, severe QoL impairment, and critical QoL impairment.
Distribution of patients according to the grades of QoL impairment before and 6 months after ASCT is shown in Table 1.
Table 1. Distribution of patients according to the grades of QoL impairment before ASCT and 6 months post-transplant (n=33)
|
QoL impairment grade |
N, % |
|
|---|---|---|
|
Before ASCT |
After ASCT |
|
|
No QoL impairment |
9 (27) |
17 (52) |
|
Mild QoL impairment |
4 (13) |
3 (9) |
|
Moderate QoL impairment |
1 (3) |
4 (13) |
|
Severe QoL impairment |
10 (30) |
7 (20) |
|
Critical QoL impairment |
9 (27) |
2 (6 |
Changes in the distribution of patients according to the grades of QoL impairment took place after ASCT. The number of patients with no QoL impairment increased after transplantation, while the number of patients with critical QoL impairment decreased. Notably, ASCT resulted in a two-fold increase in the number of patients with QoL comparable to population norms: before transplantation 27% of patients had no QoL impairment, and 6 months after ASCT it was 52%. At the same time the number of patients with critical QoL impairment had experienced a triple decrease: at base-line 27% of patients had critical QoL impairment, and 6 months after ASCT it was only 6%.
Thus, ASCT is accompanied by an increase in the number of patients with no QoL impairment and a decrease in the number of patients with critical QoL impairment.
Symptoms in MS patients after ASCT
Symptom prevalence in MS patients before and after ASCT is presented in Fig. 5. Before transplantation MS patients experienced a wide range of symptoms. The most prevalent symptom was fatigue (83%). Of those who had fatigue about half of the patients reported it at moderate-to-severe level. The other frequent symptoms were toddling, heat sensitivity, psychological problems (anxiety and sadness) and numbness/tingling with their prevalence of 79%, 76%, 72%, and 70%, respectively. More than half of the patients reported these symptoms at the moderate-to-severe level. The majority of patients (60% on average) experienced such symptoms as movement disorders, coordination problems, urination dysfunction, and vision impairment.
In response to treatment, changes in symptom prevalence in MS patients were found. Positive changes in prevalence of the most frequent symptoms – fatigue, toddling, psychological problems (anxiety and sadness), numbness/tingling, movement disorders, coordination problems, urination dysfunction, and vision impairment – were observed 6 months after ASCT. The prevalence of the vast majority of moderate-to-severe symptoms after transplantation was lower than before treatment.
Figure 5. Symptom prevalence in MS patients before ASCT and 6 months post-transplant
Information about symptom severity in MS patients before and 6 months after ASCT is presented in Table 2. Before transplantation the most severe symptom was toddling followed by heat sensitivity, fatigue, movement disorders, and coordination disorders. In response to treatment, the severity of these symptoms decreased. As it is seen from the table the mean value of the severity of these symptoms 6 months after ASCT was lower than before treatment. The severity of other symptoms decreased as well.
Table 2. Symptom severity in MS patients before ASCT and 6 months post-transplant
|
Symptoms |
Before ASCT |
6 months after ASCT |
|---|---|---|
|
Mean (SD) |
Meand (SD) |
|
|
Toddling |
5.3(4.1) |
4.2(4.0) |
|
Heat sensitivity |
4.7(3.7) |
4.5(3.8) |
|
Fatigue |
4.4(3.1) |
3.5(3.0) |
|
Movement disorders |
3.9(3.8) |
3.2(3.8) |
|
Coordination disorders |
3.7(3.8) |
3.0(3.8) |
|
Urination dysfunction |
3.3(3.8) |
1.9(2.8) |
|
Numbness/tingling |
3.3(3.3) |
1.8(2.4) |
|
Stool problems |
3.2(3.6) |
2.4(3.4) |
|
Anxiety |
3.0(2.9) |
1.8(2.7) |
|
Vision impairment |
2.8(3.4) |
1.9(3.1) |
|
Sadness |
2.8(3.0) |
1.6(2.7) |
|
Dizziness |
2.3(2.9) |
1.2(2.0) |
|
Muscle cramps |
2.1(3.0) |
2.0(3.0) |
|
Sexual dysfunction |
2.0(3.7) |
1.4(2.9) |
|
Pain |
1.5(2.2) |
1.2(2.1) |
|
Decreased concentration |
1.3(1.9) |
1.4(2.5) |
|
Memory loss |
1.1(2.0) |
1.2(2.3) |
|
Tremor |
1.1(1.9) |
0.9(2.0) |
|
Chills |
0.8(1.9) |
1.3(2.7) |
|
Speech disorders |
0.7(1.9) |
0.9(1.8) |
|
Hearing disorders |
0.5(1.7) |
0.4(1.6) |
|
Swallowing problems |
0.4(0.8) |
0.3(1.1) |
QoL treatment response in MS patients after ASCT
QoL treatment response characterizes changes in physical, psychological, and social functioning of a patient after treatment. Three types of QoL treatment response after ASCT can be identified: improvement, stabilization, and worsening.
QoL treatment response was determined at different time-points after ASCT. Here we present the data on QoL treatment response at 6 months post-transplant (n=33). Three types of QoL treatment response were registered: improvement, stabilization, or worsening. QoL improvement or QoL stabilization was shown in the vast majority of patients. QoL improvement was achieved in 16 (48.5%) patients; and QoL stabilization in other 16 patients. QoL worsening was noticed in one patient only.
Thus, the vast majority of patients (97%) experienced either QoL improvement or QoL stabilization in 6 months after ASCT.
Conclusions
1. Physical, psychological and social functioning in MS patients is significantly deteriorated. The quality of life profile of these patients is characterized by compression and deformation. The majority of patients exhibit either severe or critical QoL impairment.
2. MS patients experience a wide range of disease-related symptoms. The most frequent symptoms – fatigue, toddling, heat sensitivity, psychological problems (anxiety and sadness), and numbness/tingling – are present in more than 70% of patients. About a half of the patients report these symptoms at the moderate-to-severe level.
3. ASCT in MS patients improves their physical, psychological and social function. The most definite improvement of quality of life takes place in a year after transplantation.
4. After ASCT the number of patients with no QoL impairment increases whereas the number of patients with critical QoL impairment decreases.
5. Quality of life treatment response (QoL improvement or QoL stabilization) was achieved in the vast majority of MS patients after ASCT.
6. ASCT is associated with decline of symptom prevalence and severity in MS patients.
References
2. FDA Guidance for Industry: Patient-reported outcome measures: use in medical product development to support labeling claims. Bulletin of the Multinational Center of Quality of Life Research. 2006;7-8:153-154.
3. Fedorenko DA, Kishtovich AV, Ionova TI, Novik АА. Symptom assessment in patients with multiple sclerosis after hematopoietic stem cell transplantation. Bulletin of the Multinational Center of Quality of Life Research. 2008;11-12:157-158.
5. Nortvedt MW, Riise T, Myhr KM, et al. Quality of life as a predictor for change in disability in MS. Neurology. 2000 Jul 12;55(1):51-4.
6. Nortvedt MW, Riise T, Myhr KM, et al. Quality of life in multiple sclerosis: measuring the disease effects more broadly. // Neurology. 1999;22(53):1098-1103.
7. Novik AA, Ionova TI. Guidelines of quality of life research in medicine. М: Olma Media Grupp, 2007.
8. Novik AA, Ionova TI, Kalyadina SA, Kishtovich AV. Conceptual and statistical models of stratification of the patients population according to the grades of quality of life impairement. Bulletin of the Multinational Center of Quality of Life Research. 2007;9-10:88-98.
10. Rice GP, Oger J, Duquette P, et al. Treatment with interferon beta-1b improves quality of life in multiple sclerosis. // Can. J. Neurol. Sci. 1999;26(4):276-282.
11. The Canadian Burden of Illness Study Group. Burden of illness of multiple sclerosis: Part II: Quality of life. // Can. J. Neurol. Sci. 1998;25:31-38.
" ["DETAIL_TEXT_TYPE"]=> string(4) "html" ["~DETAIL_TEXT_TYPE"]=> string(4) "html" ["PREVIEW_TEXT"]=> string(0) "" ["~PREVIEW_TEXT"]=> string(0) "" ["PREVIEW_TEXT_TYPE"]=> string(4) "text" ["~PREVIEW_TEXT_TYPE"]=> string(4) "text" ["PREVIEW_PICTURE"]=> NULL ["~PREVIEW_PICTURE"]=> NULL ["LANG_DIR"]=> string(4) "/ru/" ["~LANG_DIR"]=> string(4) "/ru/" ["SORT"]=> string(3) "500" ["~SORT"]=> string(3) "500" ["CODE"]=> string(100) "otsenki-dannye-patsientami-s-rasseyannym-sklerozom-posle-autologichnoy-transplantatsii-stvolovykh-kr" ["~CODE"]=> string(100) "otsenki-dannye-patsientami-s-rasseyannym-sklerozom-posle-autologichnoy-transplantatsii-stvolovykh-kr" ["EXTERNAL_ID"]=> string(4) "1375" ["~EXTERNAL_ID"]=> string(4) "1375" ["IBLOCK_TYPE_ID"]=> string(7) "journal" ["~IBLOCK_TYPE_ID"]=> string(7) "journal" ["IBLOCK_CODE"]=> string(7) "volumes" ["~IBLOCK_CODE"]=> string(7) "volumes" ["IBLOCK_EXTERNAL_ID"]=> string(1) "2" ["~IBLOCK_EXTERNAL_ID"]=> string(1) "2" ["LID"]=> string(2) "s2" ["~LID"]=> string(2) "s2" ["EDIT_LINK"]=> NULL ["DELETE_LINK"]=> NULL ["DISPLAY_ACTIVE_FROM"]=> string(0) "" ["IPROPERTY_VALUES"]=> array(18) { ["ELEMENT_META_TITLE"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["ELEMENT_META_KEYWORDS"]=> string(179) "рассеянный склероз аутологичная трансплантация стволовых клеток (АТСКК) качество жизни симптомы" ["ELEMENT_META_DESCRIPTION"]=> string(316) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клетокPatient-reported outcomes in multiple sclerosis patients undergoing autologous stem cell transplantation" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(2448) "<p class="bodytext">Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести. </p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["SECTION_META_TITLE"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" ["SECTION_META_KEYWORDS"]=> string(212) "Оценки, данные пациентами с рассеянным склерозом после аутологичной трансплантации стволовых кроветворных клеток" 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Ионова, Денис А. Федоренко, Никита Е. Мочкин, Кира А. Курбатова, Андрей А. Новик</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(170) "Татьяна И. Ионова, Денис А. Федоренко, Никита Е. Мочкин, Кира А. Курбатова, Андрей А. Новик
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18436" ["VALUE"]=> array(2) { ["TEXT"]=> string(2448) "<p class="bodytext">Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2418) "Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести.
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Correspondence
Tatyana I. Ionova, 195009, Finski per., 9, mailbox 57, St. Petersburg, Russia
Phone/Fax: +7 (812) 436-61-12, E-mail: qlife@rambler.ru
Physical, psychological, and social function in MS patients is significantly deteriorated. Quality of life profile of the patients is characterized by compression and deformation. The majority of the patients exhibit either severe or critical QoL impairment. MS patients experience a wide range of disease-related symptoms; the most frequent symptoms are fatigue, toddling, heat sensitivity, psychological problems (anxiety and sadness), and numbness/tingling are present in more than 70% of patients. About half of all patients report these symptoms at the moderate-to-severe level. ASCT in MS patients improves their physical, psychological, and social function. The most definite improvement of quality of life takes place within a year of transplantation. After ASCT the number of patients with no QoL impairment increases and the number of patients with critical QoL impairment decreases. Quality of life treatment response was achieved in the vast majority of MS patients after ASCT. ASCT is associated with decline of symptom prevalence and severity in MS patients.
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Ionova<sup>1</sup>, Denis A. Fedorenko<sup>2</sup>, Nikita E. Mochkin<sup>2</sup>, Kira A. Kurbatova<sup>1</sup>, Andrey A. Novik<sup>2</sup> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(164) "Tatyana I. Ionova1, Denis A. Fedorenko2, Nikita E. Mochkin2, Kira A. Kurbatova1, Andrey A. Novik2
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Correspondence
Tatyana I. Ionova, 195009, Finski per., 9, mailbox 57, St. Petersburg, Russia
Phone/Fax: +7 (812) 436-61-12, E-mail: qlife@rambler.ru
1Multinational Center for Quality of Life Research, St. Petersburg, Russia; 2Department of Hematology and Cellular Therapy, Pirogov National Medical Surgical Center, Moscow, Russia
Correspondence
Tatyana I. Ionova, 195009, Finski per., 9, mailbox 57, St. Petersburg, Russia
Phone/Fax: +7 (812) 436-61-12, E-mail: qlife@rambler.ru
Татьяна И. Ионова, Денис А. Федоренко, Никита Е. Мочкин, Кира А. Курбатова, Андрей А. Новик
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Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2418) "Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести.
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(2418) "Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести.
" } } } [8]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "76" ["~IBLOCK_SECTION_ID"]=> string(2) "76" ["ID"]=> string(4) "1382" ["~ID"]=> string(4) "1382" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(189) "М2-подобные макрофаги у человека: потенциальные кандидаты для стимуляции репаративных процессов в ЦНС?" ["~NAME"]=> string(189) "М2-подобные макрофаги у человека: потенциальные кандидаты для стимуляции репаративных процессов в ЦНС?" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(19) "25.09.2017 11:04:00" ["~TIMESTAMP_X"]=> string(19) "25.09.2017 11:04:00" ["DETAIL_PAGE_URL"]=> string(135) "/ru/archive/tom-2-nomer-2-6/stati/m2-podobnye-makrofagi-u-cheloveka-potentsialnye-kandidaty-dlya-stimulyatsii-reparativnykh-protsessov/" ["~DETAIL_PAGE_URL"]=> string(135) "/ru/archive/tom-2-nomer-2-6/stati/m2-podobnye-makrofagi-u-cheloveka-potentsialnye-kandidaty-dlya-stimulyatsii-reparativnykh-protsessov/" ["LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["~LIST_PAGE_URL"]=> string(12) "/ru/archive/" ["DETAIL_TEXT"]=> string(57677) "Introduction
Following injury to the nervous system, the activation of the immune system profoundly affects the ability of neurons to survive and to regenerate damaged axons. The role of immune response is controversial. It has long been established that immune cells in the CNS can cause or augment tissue injury. However, recent investigations show that immune cells and their factors can contribute to neuroprotection and neuroregeneration. This dual role of the immune system is determined by the type and duration of the immune response and the balance between destructive and protective factors that ultimately define the net result of the neuro-immune interaction [5].
The immune system operates via innate (antigen-independent) and adaptive (antigen-specific) immunity. Inflammatory responses during traumatic injury or different CNS diseases are dominated by cells of the innate immune system, most importantly resident microglia and blood-borne macrophages. After phagocytosing cellular debris, microglia/macrophages present antigens to lymphocytes, thereby activating the antigen-specific immune response [33].
Unlike most other systems, the central nervous system has a limited capacity for regeneration. While the inhibitory effects of proteoglycans and myelin on axonal growth have been well established, the role of neuroinflammation in regeneration failure remains highly controversial [6]. Several studies have demonstrated the beneficial effects of macrophages (Mφ) following injury [<23, 25, 27, 37]; however, others revealed that macrophages promoted injury [9, 19].
One of the possible explanations of these diverse macrophage effects could be connected with the differences between the macrophages used. Certainly, Mφ are remarkable for the heterogeneity and diverse biological activities [11]. There are at least two distinct functional Mφ subsets that are triggered in response to different stimuli: classical pro-inflammatory and nonclassical anti-inflammatory macrophages, also termed type 1 (M1) and type 2 (M2) macrophages. M1 are induced by IFN-γ, either alone or in concert with a microbial stimulus, possess high antigen-presented activity, and support Th1 response. These cells are involved in pro-inflammatory responses, mediate resistance to intracellular pathogens and anti-tumor resistance and are tissue destructive. In contrast, various forms of M2, generated in the presence IL-4 or IL-13, immune complexes, IL-10, etc., are not efficient at antigen presentation, suppress Th1 and/or favor Th2 response, and produce high levels of matrix-associated proteins. These cells are tolerogenic and generally oriented toward resistance to parasites, immunoregulation, tissue remodeling and repair, and tumor promotion [20, 10, 18]. It is important to note that macrophages can reversibly shift their functional phenotype in response to changes in their microenvironment. Sequential treatment of macrophages with multiple cytokines results in a progression through various functional phenotypes. That is, macrophages may progress from one functional phenotype to another [32, 21].
Recently, Kigerl et al has shown that in CNS injury rapidly induced M1 response than shift to M2 response. M1 were neurotoxic, whereas M2 promoted a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominated sites of CNS injury (e.g., proteoglycans and myelin). The authors concluded that switching macrophages toward an M2 phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury [14]. Thus, boosting or modulating the immune response seems to be a promising strategy for successful CNS repair.
Since macrophages may be prospective candidates for cell therapy, the development of simple and reproducible technologies of M2-like macrophage generation seems to be a necessary step for the clinical application of this approach. For human monocytes GM-CSF treatment leads to the formation of Mφ1 macrophages with features of pro-inflammatory M1 cells, while the equivalent population following culture in M-CSF has been termed Mφ2 macrophages with features of M2 anti-inflammatory cells [34, 35]. In addition, macrophages that ingest apoptotic cells are shown to decrease pro-inflammatory and acquire anti-inflammatory properties [8]. Utilizing of M2-like macrophages in experimental models and clinical trail was successfully demonstrated by the Michel Schwartz group [27, 16]. Recently we developed a simple approach for generation of non-classical type2-like macrophages (Mφ3) in the presence of GM-CSF in serum-deficient conditions. The purpose of the current study was to compare the phenotype and functions of these Mφ3 with “standard” pro-inflammatory Mφ1 and anti-inflammatory Mφ2 subsets, generated in the presence of GM-CSF and M-CSF.
Materials and Methods
Isolation and generation of macrophages
Human blood samples were obtained from healthy donors with informed consent according to the policy approved by the local Ethical Committee. Human peripheral blood mononuclear cells (PBMCs) were obtained through density gradient centrifugation (Ficoll-Paque, Sigma-Aldrich) of heparinized whole blood samples. For monocyte separation PBMCs were plated at 3–5 x106/ml in tissue culture dishes (TPP, Switzerland) in RPMI-1640 (Sigma-Aldrich) with 5% FCS (Biolot, Russia) for 18 h and then washed to remove non-adherent residual lymphocytes. The percentage of CD14-positive cells was demonstrated by flow cytometry analysis to be greater than 90–93% of the total cells recovered.
Classical type-1 macrophages (Mφ1) were generated by culturing adherent cells in six-well tissue plates (Nunclon, Denmark) in RPMI-1640 supplemented with 5% autologous plasma, 2% FCS, 0.05 mM 2-mercaptoethanol, 2 mM sodium pyruvate, 0.3 mg/ml L-glutamine (all reagents of Sigma-Aldrich), 1% nonessential amino acids, 100 μg/ml gentamycin and 50 ng/ml recombinant human GM-CSF (R&D Systems) at 37°C with 5% CO2 for 7 days. Non-classical type 2 macrophages (Mφ2) were obtained in identical culture conditions in complete RPMI-1640 supplemented with rhM-CSF (50 ng/ml; R&D Systems). Non-classical type 3 macrophages (Mφ3) were generated by incubation of monocytes in serum growth factors deficiency conditions. Specifically, adherent cells were cultured for 7 days in complete RPMI-1640 supplemented with 2% autologous plasma (without FCS) and 50 ng/ml rhGM-CSF. Polarized Mφ (Mφ1, -2, -3) were harvested by using EDTA in Hanks' balanced salt solution, washed and counted.
Flow cytometry analysis
For evaluation of the Mφ phenotype, cell suspensions were incubated for 20 min at 4°C with fluorescein isothiocyanate (FITC) or phycoerythrin (PE)-conjugated antibodies specific for human CD14, CD86, CD90, and HLA-DR or isotype controls. All monoclonal antibodies were obtained from BD Biosciences (USA). After incubation with antibodies, cells were washed with PBS containing 0.1% sodium azide (Sigma-Aldrich) and 0.1% bovine serum albumin, and were then analyzed with a FACSCalibur using CellQuest software (BD Biosciences).
T-cell proliferation assays
The antigen-presenting and allostimulatory activity of Mφ was determined by measuring T-cell proliferation in the mixed lymphocyte culture (MLC). Different types of Mφ were collected after generation and 1x105 cells were then plated in RPMI-1640 supplemented with 0.3 mg/ml L-glutamine, 5 mM HEPES buffer, 100 μg/ml gentamycin and 10% inactivated donor serum (AB (IV) group), and added to 1x106 allogeneic responder PBMCs. All cultures were carried out in triplicate in round-bottom 96-well tissue culture plates, in a final volume of 150 μl of RPMI complete medium. T-cell proliferation was assessed after 5 days by adding [3H]thymidine (1 μCi/well) for 18 h. Cells were then harvested and thymidine incorporation was measured in a liquid scintillation counter SL-30 (Intertechnic, France). The stimulatory capacity of Mφ in MLC was expressed by the stimulation index (SI) = cpm in MLC (PBMCs+Mφ) / cpm in control culture (PBMCs alone).
Cytokines, chemokines, and growth factor measurements
Culture supernatants of generated Mφ (Mφ1, -2, -3) were collected and stored at –80°C prior to measurement. The concentration of secreted cytokines/chemokines was determined by using the Bio-Plex Protein Array System (kits and equipment of Bio-Rad, USA based on Luminex xMAP technology; sensitivity 2 pg/ml) in the case of TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G-CSF, IFN-γ, IL-8, MCP-1, and MIP-1β, and by using ELISAs from Diagnostic System Laboratories for insulin-like growth factor-I (IGF-I, sensitivity 0.01 ng/ml); from BioSource for basic fibroblast growth factor (FGF-basic, sensitivity 7 pg/ml); from R&D Systems for brain-derived neurotrophic factor (BDNF, sensitivity 20 pg/ml); from Invitrogen Corp. for vascular endothelial growth factor (VEGF, sensitivity 5 pg/ml); from Protein Contour (St-Petersburg, Russia) for erythropoietin (EPO, sensitivity 4 pg/ml) and epidermal growth factor (EGF, sensitivity 2 pg/ml); and from Vector-Best (Novosibirsk, Russia) for IL-18 (sensitivity 5 pg/ml).
Statistical analysis
Statistical analysis was performed using the STATISTICA software version 6.0 (StatSoft. Inc., USA). The Mann-Whitney non-parametric two-tailed U test was used to determine the significance of data, which are presented as median and inter-quartile range (IQR). Values of p < 0.05 were considered statistically significant.
Results
Characterization of generated Mφ
We generated three distinct Mφ subsets in vitro from peripheral blood monocytes and performed a series of parallel comparisons between them. As a first step, we measured cell yield and their phenotype. The number of Mφ1 and Mφ2 obtained from 1x106 PBMCs was 3.35x104 (IQR 2.2–7.4x104) and 2.50x104 (IQR 1.4–4.5x104), whereas Mφ3 yield was significantly higher – 5.0x104 (IQR 3.3– 0.4x104, pU<0.01), indicating that a low serum condition increased the quantity of macrophages generated in the presence of GM-CSF.
After 7 days of culture, the majority of Mφ1, Mφ2, and Mφ3 were adherent cells with a classical “fried egg” morphology (data not shown) that expressed CD14 on their cell surface (Table 1). A small number of adherent cells had a stretched, spindle-like morphology (fibroblast-like cells). The average number of these cells in Mφ1 (n=8) and Mφ2 (n=8) populations was similar and constituted 25% (IQR 22–45 and 16.5–33.5%, respectively), and was slightly higher (Median 32.5%, IQR 17–43%, n=6) in the Mφ3 subset. However, the expression of CD90 antigen (a typical marker for a fibroblasts and mesenchymal stem cells) in all Mφ populations was low and the percentage of CD90+ cells did not exceed 2–3%.
Table 1. Phenotype Mφ1, Mφ2 and Mφ3 subsets
|
Percentage of positive cell |
||||||
|---|---|---|---|---|---|---|
|
Marker |
Mφ1 |
Mφ2 |
Mφ3 |
|||
|
Median (IQR) |
N |
Median (IQR) |
N |
Median (IQR) |
N |
|
|
CD14 |
78 (70–84) |
17 |
87 (78–91) |
9 |
82 (67–92) |
25 |
|
HLA-DR |
97 (91–98) |
21 |
96 (96–98) |
9 |
87 (73–97) |
17 |
|
CD86 |
37 (23–53) |
18 |
27 (15–39) |
13 |
23 (11–58) |
17 |
|
CD90 |
2.5 (0–5.0) |
10 |
2.0 (0–5.0) |
13 |
3 (0.6–5.0) |
8 |
All three Mφ populations strongly expressed the HLA-DR antigen, though the percentage of HLA-DR positive cells in the Mφ3 cultures was lower than in the Mφ1 and Mφ2. All types of monocyte-derived macrophages also expressed the CD86 antigen. The mean number of СD86+ cells in Mφ2 and Mφ3 was lower than in Mφ1, though not significantly.
The ability of Mφ to induce T-cell proliferation
The revealed differences of HLA-DR and CD86 expression in distinct Mφ populations could influence their antigen-presenting function. To determine whether Mφ1, Mφ2, and Mφ3 differed quantitatively in their capacity to present antigen, we tested and compared their ability to induce an allogeneic T-cell response. For this purpose distinct Mφ subsets derived from the same donor were cocultured with allogeneic PBMCs over a period of 5 days, and the T-cell proliferation was determined (Table 2). Analysis of [3H]thymidine incorporation revealed a strong proliferative response in PBMCs cocultured with Mφ1, whereas weak proliferation could be observed in PBMCs cocultured with Mφ2 or Mφ3. Remarkably, the T-cell stimulatory capacity of Mφ3 expressed by the stimulation index (SI) was significantly lower than that of Mφ1 and Mφ2.
Table 2. The stimulatory effect of Mφ1, Mφ2 and Mφ3 subsets on allogeneic T-cell proliferation
|
Culture |
Mφ1 (n=24) |
Mφ2 (n=24) |
Mφ3 (n=24) |
|
|---|---|---|---|---|
|
PBMCs alone |
Median |
330 |
140 |
370 |
|
IQR |
105–720 |
105–410 |
70–1300 |
|
|
PBMCs + Mφ (10:1) |
Median |
7380 |
3130 ** |
2070 ** # |
|
IQR |
3500–13220 |
1600–3680 |
330–3230 |
|
|
Stimulation index |
Median |
19.6 |
14.8 |
3.4 ** ## |
|
IQR |
14.9–74.5 |
6.2–35.3 |
1.4–13.7 |
|
|
Mφ (1x105 cells) were cultured with 1x106 allogeneic PBMCs over 5 days. 3[H]-thymidine (1 µCi/well) was added 18 h before harvesting to measure T-cell proliferation (cpm). The stimulation index is expressed in calculated units (cpm in MLC (PBMCs+Mφ) / cpm in control culture (PBMCs alone). |
||||
Generated Mφ differ in cytokine and chemokine production
To further characterize the secretory profile of generated Mφ subsets, we measured the production of Th1/pro-inflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-12, IL-17, IL-18, IL-6) and Th2/anti-inflammatory cytokines (IL-4, IL-10, IL-13). Cytokine levels were measured in supernatants of 7-day cultures of Mφ1, Mφ2 and Mφ3. Mφ1 spontaneously produced considerable levels of IL-1β, IL-6, TNF-α, IFN- γ, IL-4, and IL-17 (Table 3). This finding confirms the pro-inflammatory nature of Mφ1 and their capacity for T-cell activation. Mφ2 were characterized by lower secretory activity for some of these cytokines, though the differences were significant only for IL-4 and IL-18. In contrast, Mφ3 displayed remarkably decreased basal levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18), Th1-cytokines (IFN-γ, IL-2), and IL-4. Mφ3 also differed from Mφ1 by a 2-fold lower IL-12 production and more pronounced production of IL-10, though not significantly. In addition to cytokines, we measured the levels of various inflammatory chemokines in the supernatants of unstimulated macrophages. Generated Mφ constitutively produced high levels of IL-8, MCP-1, and MIP-1β. Mφ1 and Mφ2 demonstrated similar levels in their production. In contrast, secretion of neutrophil-attracting IL-8 and monocyte-attracting MCP-1 by Mφ3 was significantly lower than by Mφ1 and Mφ2. However, the production of T-cell attracting MIP-1β by Mφ3 did not differ from that by Mφ1 and Mφ2. Together, these data confirm the pro-inflammatory nature of Mφ1 and significantly less pro-inflammatory activity of Mφ3.
Table 3. Cytokine/chemokine concentrations secreted by Mφ1, Mφ2, and Mφ3
|
Cytokines& |
Mφ1 (n=10) Median |
IQR |
Mφ2(n=10) Median |
IQR |
Mφ3 (n=24) Median |
IQR |
|---|---|---|---|---|---|---|
|
|
872 |
734–995 |
839 |
539–1010 |
626 * ↓ |
440–830 |
|
IL-2 |
154 |
115–154 |
115 |
70–155 |
72 *↓ |
47–115 |
|
IL-1β |
405 |
246–670 |
313 |
150–790 |
195 * # ↓ |
68–290 |
|
TNF-α |
175 |
124–282 |
148 |
55–224 |
99 * ↓ |
51–156 |
|
IL-12 |
28 |
20–29 |
19 |
7–25 |
14 |
3–33 |
|
IL-17 |
308 |
245–483 |
257 |
177–448 |
214 |
112–427 |
|
IL-18 |
33 |
29–51 |
27 * ↓ |
16.5–31.2 |
19 * ↓ |
15.7–35.8 |
|
IL-6 |
21340 |
13430–27340 |
20350 |
8380–25060 |
10900 * ↓ |
4110–21770 |
|
IL-4 |
215 |
198–246 |
119 ** ↓ |
79–141 |
106 ** ↓ |
53–190 |
|
IL-10 |
5 |
2–10 |
2 |
2–2 |
15 |
2–60 |
|
IL-13 |
78 |
37–113 |
48 |
37–78 |
78 |
42–112 |
|
IL-8 |
90380 |
74280–93340 |
67400 |
57940–94430 |
44320 ** ## ↓ |
29150–59000 |
|
MCP-1 |
11140 |
5680–14000 |
11910 |
4160–17660 |
3345 ** ## ↓ |
1100–4460 |
|
MIP-1β |
1 960 |
1250–5590 |
1 560 |
930–2700 |
2220 |
790–7620 |
|
* pU < 0.05 and ** pU < 0.01 vs Mφ1; # pU < 0.05 and ## pU < 0.01 vs Mφ2. |
||||||
Production of growth factors by generated Mφ
All three types of unstimulated macrophages secreted detectable concentrations of erythropoietin, G-CSF, FGF-basic, BDNF, and IGF-1 (Table 4). Mφ1 and Mφ2 produced analogous levels of these growth factors, although there was a strong tendency to higher production of EPO by Mφ2. Despite the decreased production of pro-inflammatory cytokines, Mφ3 secreted concentrations of G-CSF, EPO, FGF-basic and EGF comparable with Mφ2, though significantly lower concentration of BDNF. But the most prominent difference was revealed for the production of IGF-1, which was much higher in Mφ3 in comparison with Mφ1 and Mφ2 cultures. Concerning VEGF, its detectable concentrations in 7-day cultures were determined only in a quarter of tested donors. Among these cultures VEGF was predominantly produced by Mφ2, and especially by Mφ-3, but not Mφ1.
Table 4. Growth factors production by Mφ1, Mφ2 and Mφ3
Growth factors (pg/ml) | Mφ1 (n=10) | IQR | Mφ2 (n=10) | IQR | Mφ3 (n=24) | IQR |
|---|---|---|---|---|---|---|
G-CSF | 670 | 505–1610 | 730 | 315–2310 | 430 | 180–1050 |
EPO | 19.2 | 1.7–36.9 | 46.5 | 33.8–81.1 | 34.9 | 21.5–56.5 |
FGF-basic | 104 | 57–124 | 150 | 87–180 | 109 | 45–126 |
EGF | 207 | 148–331 | 283 | 245–420 | 138 | 38–310 |
BDNF | 392 | 187–705 | 438 | 215–739 | 131 * # ↓ | 78–235 |
IGF-1 | 322 | 170–8560 | 152 | 116–459 | 8310 * ## ↑ | 520–9500 |
VEGF (n=6) | 5.0 | 5.0–97 | 92.8 * ↑ | 59.2–298 | 422.4 * # ↑ | 107.7–524.7 |
* pU < 0.05 and ** pU < 0.01 vs Mφ1; # pU < 0.05 and ## pU < 0.01 vs Mφ2. | ||||||
Discussion
Over the last decade, there has been an increasing interest in the role of the inflammatory reaction in CNS injury. Moreover, this interest has focused on the dominant cell type observed during inflammation, the macrophage. However, in the CNS the contribution of these cells to the healing process remains questionable [6].
The contradictory data regarding the contribution of Mφ to CNS recovery could be explained by diverse macrophage activities, many of which appear to be oppositional in nature. The destructive potential of macrophages in CNS pathology may be caused by pro-inflammatory activity, whereas their regenerative capacity may be linked with anti-inflammatory features [12].
In the search for macrophages with potential regenerative activity we developed a simple method for the generation of macrophages in growth factor deficient conditions and analyzed the phenotype and functional activity of these macrophages, termed Mφ3, with pro-inflammatory Mφ1 and anti-inflammatory Mφ2. We speculated that the deficiency of growth factors in low serum conditions may be one of the key factors capable of activating regenerative properties of macrophages. Particularly, low serum conditions during macrophage cultivation could stimulate deprivation-induced apoptosis of culturing cells (including admixture of non-adherent cells), and the ingestion of apoptotic cells may change the functional activity of macrophages toward an anti-inflammatory phenotype.
The received data demonstrated that low serum conditions did not influence the efficacy of Mφ3 generation. Moreover, the yield of Mφ3 significantly exceeded the number of Mφ1 and Mφ2. These data are correspondent with Plesner's study, who showed an enhanced yield of M-CSF treated macrophages in cultures with 1% fetal calf serum [22].
According to study of Verreck et al, anti-inflammatory Mφ2 have a lower expression of HLA-DR and CD86 molecules after LPS stimulation, though unstimulated macrophages expressed similar levels of these molecules [34]. We have shown that as compared to Mφ1 and Mφ2, Mφ3 cultures contained lower numbers of HLA-DR and CD86-positive cells. These differences, though not statistically significant, were important for the association with the decreased capacity of Mφ3 to stimulate allogeneic T cell proliferation. Type-2 anti-inflammatory macrophages are known to have a lower ability to stimulate T-cell proliferation in MLC [11]. This is in agreement with our data, and pointed to the lower allostimulatory activity of Mφ2 in comparison with Mφ1. Notably, Mφ3 virtually failed to stimulate lymphocyte proliferation in MLC. The medium value of the Mφ3 stimulation index was more than 6-fold lower than that of Mφ1. This fact strongly suggests that generated Mφ3 are not immunogenic and in this respect resemble anti-inflammatory M2 macrophages.
To further evaluate the pro- and anti-inflammatory activity of generated macrophages we compared their capacity to spontaneous production of Th1/pro- and Th2/anti-inflammatory cytokines. In contrast to Mφ1, Mφ3 produced significantly (2-fold) lower concentrations of pro-inflammatory (IL-1β, TNF-α, IL-6, IL-18) and Th1/Th2-cytokines (IFN-γ, IL-2, IL-4). Mφ3 supernatants also contained 2-fold lower concentrations of IL-12 and higher levels of IL-10, though these differences were not statistically significant.
Gordon and coworkers [11] have described alternatively activated macrophages after treatment with IL-4 or IL-13, which produce IL-10 without microbial stimulation. At the same time the study of Verreck demonstrated that unlike alternatively activated Mφ, M-CSF polarized Mφ2 failed to release IL-10 without activation, but effectively secreted IL-10 after mycobacterial activation. However, activated Mφ-2 produced no or relatively low levels of IL-12, IL-1β, IL-6, TNF-α [34]. We also did not reveal any significant concentrations of IL-10 in the supernatants of unstimulated Mφ2. In contrast to Mφ-2, Mφ-3 spontaneously produced IL-10 and displayed significantly less pro-inflammatory phenotype (as compare with Mφ1) without any additional stimulation.
Our results are also in agreement with findings suggesting a high ability of M-CSF polarized Mφ2 to secrete pro-inflammatory chemokines [35]. Mφ3 were also shown to secrete MIP-1β levels comparable with Mφ1 and Mφ2, but lower levels of IL-8 and MCP-1. This indicated that unlike Mφ1 and Mφ2 subsets, Mφ3 has less capacity to attract neutrophils and monocytes and therefore is less effective in supporting inflammation, whereas they could recruit effector Th1 cells and modify their functions.
One possible mechanism underlying the beneficial role of macrophages in CNS repair is connected with their capacity to produce a wide range of growth factors that can promote neuroprotection and regeneration [30, 17, 6]. The comparative analysis of some growth factors in the supernatants of generated macrophages revealed that all three Mφ subsets spontaneously produced detectable levels of EPO, G-CSF, IGF-1, FGF-basic, EGF, and BDNF. Mφ3 secreted concentrations of G-CSF, FGF-basic and EGF similar to Mφ1 and Mφ2, EPO comparable with Mφ2, and a lower level of BDNF, but more than 25-fold higher level of IGF-1. As for VEGF, this growth factor, identified only in quarter of patients, was produced by both Mφ2 and Mφ3, but not Mφ-1 and was significantly higher in Mφ3- than in Mφ2 cultures.
Production of classical neurotrophic factors including CNTF, IGF, HGF, PDGF, NGF, BDNF, GDNF, and NT-3 by macrophages have been shown in numerous studies [3, 7, 13]. Evaluation of two of these factors (BDNF and IGF-1) in cultures of distinct macrophage subtypes in our study supported previous data and demonstrated comparable production of these factors by inflammatory Mφ1 and anti-inflammatory Mφ2. Moreover we have shown for the first time that in spite of a lower level of BDNF, Mφ3 were characterized with exclusively high secretion of IGF-1.
IGF-1 is a potent neurotrophic factor. Its pleiotropic effects range from classical trophic actions on neurons such as housekeeping or anti-apoptotic/pro-survival effects to modulation of brain-barrier permeability, neuronal excitability, or new neuron formation. IGF-1 is also known to significantly improve axon growth and remyelination [2, 4]. The finding that IGF-1 is secreted abundantly by Mφ3 may point toward an important potential role for these macrophages in neuroprotection and regeneration.
In addition to neurotrophic factors, generated macrophages produced significant levels of VEGF. Detection of VEGF (in 7-day macrophage supernatants) only in part of the tested donors could be connected with an earlier peak of VEGF production. Nevertheless, in detectable cases VEGF was predominantly produced by both Mφ2 and Mφ3. VEGF has direct neuroprotective effects on motoneurons, induces neurogenesis and angiogenesis and its reduced levels cause neurodegeneration in part by impairing neural tissue perfusion [31, 38].
Other factors, such as EPO, G-CSF, FGF-β, and EGF, produced by Mφ-3 and Mφ1/Mφ2 subsets could also underlay the neuro-regenerative macrophage potential. Erythropoietin functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production. This cytokine promotes both neuroprotection and neuroregeneration in various models of CNS injury and disease and is considered to be a promising candidate as neuroprotective agent [29,15]. G-CSF appears to have anti-apoptotic effect and stimulate differentiation of adult neural stem cells [26]. EGF is a motility factor for microglial cells and is shown to enhance the differentiation, maturation and survival of a variety of neurons in the central nervous system [36]. FGF-basic promotes the survival and neurite growth of brain neurons in vitro and in vivo, suggesting that it functions as a neurotrophic factor. In addition FGF acutely modulates synaptic transmission in the hippocampus, suggesting that it has a role similar to a neurotransmitter or neuromodulator [1].
Several groups have confirmed the therapeutic potential of activated microglia and monocyte derived macrophages in the injured spinal cord [3, 23-25]. The success of these pre-clinical models prompted a Phase I clinical trial that was completed without any adverse effects. Implantation of macrophages preincubated with dermis was well tolerated. Of the eight patients with complete spinal cord injury, three recovered clinically significant neurological motor and sensory function [16].
Recent study of this group showed that augmenting the naive monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Notably, the enhancement of motor functions was associated with anti-inflammatory activity of infiltrating macrophages, mediated by interleukin 10 [28].
In this aspect, the Mφ3 subset described in our study is characterized by low pro-inflammatory/immunogenic properties and high regenerative potential and therefore may represent new candidates for cell therapy in CNS injuries.
Acknowledgements
The authors declare no competing interests.
References
1. Abe, K. Effects of basic fibroblast growth factor on central nervous system functions. Pharmacol Res. 2001;43:307-302.
2. Apel PJ, Ma J, Callahan M, Northam CN, Alton TB, Sonntag WE, Li Z. Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve. 2009 Oct. 2. doi: 10.1002/mus.21485.
3. Bomstein Y, Marder JB, Vitner K, Smirnov I, Lisaey G, Butovsky O, Fulga V, Yoles E. Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol. 2003;142:10-16. doi: 10.1016/S0165-5728(03)00260-1.
4. Carro E, Trejo JL, Núñez, A, Torres-Aleman I. Brain repair and neuroprotection by serum insulin-like growth factor-I. Mol Neurobiol. 2003;27:153-162. doi: 10.1385/MN:27:2:153.
5. Correale J, Villa A. The neuroprotective role of inflammation in nervous system injuries. J Neurol. 2004;251:1304-1316. doi: 10.1007/s00415-004-0649-z.
7. Elkabes S, Dicicco-Bloom EM, Black IB. Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci. 1996;16:2508-2521. pmid: 8786427.
9. Fitch MT, Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Exp Neurol. 1997;148:587-603. doi: 10.1006/exnr.1997.6701.
10. Gordon, S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3:23-35. doi:10.1038/nri978.
11. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 2005;5:953-964. doi: 10.1038/nri1733.
12. Hohlfeld R, Kerschensteiner M, Meinl E. Dual role of inflammation in CNS disease. Neurology. 2007;68(3):58-63. pmid: 17548571.
13. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WEF, Kolbeck R, Hoppe E, Oropeza-Wekerle R-L, Bartke L, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med. 1999;189:865-870.
15. King C.E, Rodger J, Bartlett C, Esmaili T, Dunlop SA, Beazley LD. Erythropoietin is both neuroprotective and neuroregenerative following optic nerve transaction. Exp Neurol. 2007;205:48-55.
16. Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, Marder JB, Yoles E, Belkin M, Schwartz M, Hadani M. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg. 2005;3:173-181.
18. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677-686. doi:10.1016/j.it.2004.09.015.
19. McPhail LT, Stirling DP, Tetzlaff W, Kwiecien JM, Ramer MS. The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury. Eur J Neurosci. 2004;20:1984-1994. doi: 10.1111/j.1460-9568.2004.03662.x.
20. Mosser DM. The many faces of macrophage activation. J Leukocyte Biol. 2003;73:209-212.
22. Plesner A, Greenbaumb CJ, Lernmarka A. Low serum conditions for in vitro generation of human macrophages with macrophage colony stimulating factor. J Immunol Meth. 2001;249:53–61.
23. Prewitt CM, Niesman IR, Kane CJ, Houle JD. Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol. 1997;148:433-443. doi:10.1006/exnr.1997.6694.
24. Rabchevsky AG, Streit WJ. Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res. 1997;47:34-48. doi: 10.1002/(SICI)1097-4547(19970101)47:1<34::AID-JNR4>3.0.CO;2-G.
25. Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 1998;4:814-821. pmid: 9662373.
27. Schwartz M, Lazarov-Spiegler O, Rapalino O, Agranov I, Velan G, Hadani M. Potential repair of rat spinal cord injuries using stimulated homologous macrophages. Neurosurgery. 1999;44:1041-1045. pmid: 10232537.
29. Spate CK, Krampe H, Ehrenreich H. Recombinant human erythropoietin: novel strategies for neuroprotective/neuroregenerative treatment of multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2008;1:193-206.
30. Stoll G, Jander S, Schroeter M. Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol. 2002;513:87-113. pmid: 12575818.
33. Turrin NP, Rivest S. Molecular and cellular immune mediators of neuroprotection. Molecular Neurobiology. 2006;34:221-242. doi: 10.1385/MN:34:3:221.
36. Wing R, Wong C, Guillaud L. The role of epidermal growth factor and its receptors in mammalian CNS. Cytokines & Growth factors. 2004;15:147-156.
38. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, van Bruggen N, Chopp M. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106:829-838.
" ["~DETAIL_TEXT"]=> string(57677) "Introduction
Following injury to the nervous system, the activation of the immune system profoundly affects the ability of neurons to survive and to regenerate damaged axons. The role of immune response is controversial. It has long been established that immune cells in the CNS can cause or augment tissue injury. However, recent investigations show that immune cells and their factors can contribute to neuroprotection and neuroregeneration. This dual role of the immune system is determined by the type and duration of the immune response and the balance between destructive and protective factors that ultimately define the net result of the neuro-immune interaction [5].
The immune system operates via innate (antigen-independent) and adaptive (antigen-specific) immunity. Inflammatory responses during traumatic injury or different CNS diseases are dominated by cells of the innate immune system, most importantly resident microglia and blood-borne macrophages. After phagocytosing cellular debris, microglia/macrophages present antigens to lymphocytes, thereby activating the antigen-specific immune response [33].
Unlike most other systems, the central nervous system has a limited capacity for regeneration. While the inhibitory effects of proteoglycans and myelin on axonal growth have been well established, the role of neuroinflammation in regeneration failure remains highly controversial [6]. Several studies have demonstrated the beneficial effects of macrophages (Mφ) following injury [<23, 25, 27, 37]; however, others revealed that macrophages promoted injury [9, 19].
One of the possible explanations of these diverse macrophage effects could be connected with the differences between the macrophages used. Certainly, Mφ are remarkable for the heterogeneity and diverse biological activities [11]. There are at least two distinct functional Mφ subsets that are triggered in response to different stimuli: classical pro-inflammatory and nonclassical anti-inflammatory macrophages, also termed type 1 (M1) and type 2 (M2) macrophages. M1 are induced by IFN-γ, either alone or in concert with a microbial stimulus, possess high antigen-presented activity, and support Th1 response. These cells are involved in pro-inflammatory responses, mediate resistance to intracellular pathogens and anti-tumor resistance and are tissue destructive. In contrast, various forms of M2, generated in the presence IL-4 or IL-13, immune complexes, IL-10, etc., are not efficient at antigen presentation, suppress Th1 and/or favor Th2 response, and produce high levels of matrix-associated proteins. These cells are tolerogenic and generally oriented toward resistance to parasites, immunoregulation, tissue remodeling and repair, and tumor promotion [20, 10, 18]. It is important to note that macrophages can reversibly shift their functional phenotype in response to changes in their microenvironment. Sequential treatment of macrophages with multiple cytokines results in a progression through various functional phenotypes. That is, macrophages may progress from one functional phenotype to another [32, 21].
Recently, Kigerl et al has shown that in CNS injury rapidly induced M1 response than shift to M2 response. M1 were neurotoxic, whereas M2 promoted a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominated sites of CNS injury (e.g., proteoglycans and myelin). The authors concluded that switching macrophages toward an M2 phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury [14]. Thus, boosting or modulating the immune response seems to be a promising strategy for successful CNS repair.
Since macrophages may be prospective candidates for cell therapy, the development of simple and reproducible technologies of M2-like macrophage generation seems to be a necessary step for the clinical application of this approach. For human monocytes GM-CSF treatment leads to the formation of Mφ1 macrophages with features of pro-inflammatory M1 cells, while the equivalent population following culture in M-CSF has been termed Mφ2 macrophages with features of M2 anti-inflammatory cells [34, 35]. In addition, macrophages that ingest apoptotic cells are shown to decrease pro-inflammatory and acquire anti-inflammatory properties [8]. Utilizing of M2-like macrophages in experimental models and clinical trail was successfully demonstrated by the Michel Schwartz group [27, 16]. Recently we developed a simple approach for generation of non-classical type2-like macrophages (Mφ3) in the presence of GM-CSF in serum-deficient conditions. The purpose of the current study was to compare the phenotype and functions of these Mφ3 with “standard” pro-inflammatory Mφ1 and anti-inflammatory Mφ2 subsets, generated in the presence of GM-CSF and M-CSF.
Materials and Methods
Isolation and generation of macrophages
Human blood samples were obtained from healthy donors with informed consent according to the policy approved by the local Ethical Committee. Human peripheral blood mononuclear cells (PBMCs) were obtained through density gradient centrifugation (Ficoll-Paque, Sigma-Aldrich) of heparinized whole blood samples. For monocyte separation PBMCs were plated at 3–5 x106/ml in tissue culture dishes (TPP, Switzerland) in RPMI-1640 (Sigma-Aldrich) with 5% FCS (Biolot, Russia) for 18 h and then washed to remove non-adherent residual lymphocytes. The percentage of CD14-positive cells was demonstrated by flow cytometry analysis to be greater than 90–93% of the total cells recovered.
Classical type-1 macrophages (Mφ1) were generated by culturing adherent cells in six-well tissue plates (Nunclon, Denmark) in RPMI-1640 supplemented with 5% autologous plasma, 2% FCS, 0.05 mM 2-mercaptoethanol, 2 mM sodium pyruvate, 0.3 mg/ml L-glutamine (all reagents of Sigma-Aldrich), 1% nonessential amino acids, 100 μg/ml gentamycin and 50 ng/ml recombinant human GM-CSF (R&D Systems) at 37°C with 5% CO2 for 7 days. Non-classical type 2 macrophages (Mφ2) were obtained in identical culture conditions in complete RPMI-1640 supplemented with rhM-CSF (50 ng/ml; R&D Systems). Non-classical type 3 macrophages (Mφ3) were generated by incubation of monocytes in serum growth factors deficiency conditions. Specifically, adherent cells were cultured for 7 days in complete RPMI-1640 supplemented with 2% autologous plasma (without FCS) and 50 ng/ml rhGM-CSF. Polarized Mφ (Mφ1, -2, -3) were harvested by using EDTA in Hanks' balanced salt solution, washed and counted.
Flow cytometry analysis
For evaluation of the Mφ phenotype, cell suspensions were incubated for 20 min at 4°C with fluorescein isothiocyanate (FITC) or phycoerythrin (PE)-conjugated antibodies specific for human CD14, CD86, CD90, and HLA-DR or isotype controls. All monoclonal antibodies were obtained from BD Biosciences (USA). After incubation with antibodies, cells were washed with PBS containing 0.1% sodium azide (Sigma-Aldrich) and 0.1% bovine serum albumin, and were then analyzed with a FACSCalibur using CellQuest software (BD Biosciences).
T-cell proliferation assays
The antigen-presenting and allostimulatory activity of Mφ was determined by measuring T-cell proliferation in the mixed lymphocyte culture (MLC). Different types of Mφ were collected after generation and 1x105 cells were then plated in RPMI-1640 supplemented with 0.3 mg/ml L-glutamine, 5 mM HEPES buffer, 100 μg/ml gentamycin and 10% inactivated donor serum (AB (IV) group), and added to 1x106 allogeneic responder PBMCs. All cultures were carried out in triplicate in round-bottom 96-well tissue culture plates, in a final volume of 150 μl of RPMI complete medium. T-cell proliferation was assessed after 5 days by adding [3H]thymidine (1 μCi/well) for 18 h. Cells were then harvested and thymidine incorporation was measured in a liquid scintillation counter SL-30 (Intertechnic, France). The stimulatory capacity of Mφ in MLC was expressed by the stimulation index (SI) = cpm in MLC (PBMCs+Mφ) / cpm in control culture (PBMCs alone).
Cytokines, chemokines, and growth factor measurements
Culture supernatants of generated Mφ (Mφ1, -2, -3) were collected and stored at –80°C prior to measurement. The concentration of secreted cytokines/chemokines was determined by using the Bio-Plex Protein Array System (kits and equipment of Bio-Rad, USA based on Luminex xMAP technology; sensitivity 2 pg/ml) in the case of TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G-CSF, IFN-γ, IL-8, MCP-1, and MIP-1β, and by using ELISAs from Diagnostic System Laboratories for insulin-like growth factor-I (IGF-I, sensitivity 0.01 ng/ml); from BioSource for basic fibroblast growth factor (FGF-basic, sensitivity 7 pg/ml); from R&D Systems for brain-derived neurotrophic factor (BDNF, sensitivity 20 pg/ml); from Invitrogen Corp. for vascular endothelial growth factor (VEGF, sensitivity 5 pg/ml); from Protein Contour (St-Petersburg, Russia) for erythropoietin (EPO, sensitivity 4 pg/ml) and epidermal growth factor (EGF, sensitivity 2 pg/ml); and from Vector-Best (Novosibirsk, Russia) for IL-18 (sensitivity 5 pg/ml).
Statistical analysis
Statistical analysis was performed using the STATISTICA software version 6.0 (StatSoft. Inc., USA). The Mann-Whitney non-parametric two-tailed U test was used to determine the significance of data, which are presented as median and inter-quartile range (IQR). Values of p < 0.05 were considered statistically significant.
Results
Characterization of generated Mφ
We generated three distinct Mφ subsets in vitro from peripheral blood monocytes and performed a series of parallel comparisons between them. As a first step, we measured cell yield and their phenotype. The number of Mφ1 and Mφ2 obtained from 1x106 PBMCs was 3.35x104 (IQR 2.2–7.4x104) and 2.50x104 (IQR 1.4–4.5x104), whereas Mφ3 yield was significantly higher – 5.0x104 (IQR 3.3– 0.4x104, pU<0.01), indicating that a low serum condition increased the quantity of macrophages generated in the presence of GM-CSF.
After 7 days of culture, the majority of Mφ1, Mφ2, and Mφ3 were adherent cells with a classical “fried egg” morphology (data not shown) that expressed CD14 on their cell surface (Table 1). A small number of adherent cells had a stretched, spindle-like morphology (fibroblast-like cells). The average number of these cells in Mφ1 (n=8) and Mφ2 (n=8) populations was similar and constituted 25% (IQR 22–45 and 16.5–33.5%, respectively), and was slightly higher (Median 32.5%, IQR 17–43%, n=6) in the Mφ3 subset. However, the expression of CD90 antigen (a typical marker for a fibroblasts and mesenchymal stem cells) in all Mφ populations was low and the percentage of CD90+ cells did not exceed 2–3%.
Table 1. Phenotype Mφ1, Mφ2 and Mφ3 subsets
|
Percentage of positive cell |
||||||
|---|---|---|---|---|---|---|
|
Marker |
Mφ1 |
Mφ2 |
Mφ3 |
|||
|
Median (IQR) |
N |
Median (IQR) |
N |
Median (IQR) |
N |
|
|
CD14 |
78 (70–84) |
17 |
87 (78–91) |
9 |
82 (67–92) |
25 |
|
HLA-DR |
97 (91–98) |
21 |
96 (96–98) |
9 |
87 (73–97) |
17 |
|
CD86 |
37 (23–53) |
18 |
27 (15–39) |
13 |
23 (11–58) |
17 |
|
CD90 |
2.5 (0–5.0) |
10 |
2.0 (0–5.0) |
13 |
3 (0.6–5.0) |
8 |
All three Mφ populations strongly expressed the HLA-DR antigen, though the percentage of HLA-DR positive cells in the Mφ3 cultures was lower than in the Mφ1 and Mφ2. All types of monocyte-derived macrophages also expressed the CD86 antigen. The mean number of СD86+ cells in Mφ2 and Mφ3 was lower than in Mφ1, though not significantly.
The ability of Mφ to induce T-cell proliferation
The revealed differences of HLA-DR and CD86 expression in distinct Mφ populations could influence their antigen-presenting function. To determine whether Mφ1, Mφ2, and Mφ3 differed quantitatively in their capacity to present antigen, we tested and compared their ability to induce an allogeneic T-cell response. For this purpose distinct Mφ subsets derived from the same donor were cocultured with allogeneic PBMCs over a period of 5 days, and the T-cell proliferation was determined (Table 2). Analysis of [3H]thymidine incorporation revealed a strong proliferative response in PBMCs cocultured with Mφ1, whereas weak proliferation could be observed in PBMCs cocultured with Mφ2 or Mφ3. Remarkably, the T-cell stimulatory capacity of Mφ3 expressed by the stimulation index (SI) was significantly lower than that of Mφ1 and Mφ2.
Table 2. The stimulatory effect of Mφ1, Mφ2 and Mφ3 subsets on allogeneic T-cell proliferation
|
Culture |
Mφ1 (n=24) |
Mφ2 (n=24) |
Mφ3 (n=24) |
|
|---|---|---|---|---|
|
PBMCs alone |
Median |
330 |
140 |
370 |
|
IQR |
105–720 |
105–410 |
70–1300 |
|
|
PBMCs + Mφ (10:1) |
Median |
7380 |
3130 ** |
2070 ** # |
|
IQR |
3500–13220 |
1600–3680 |
330–3230 |
|
|
Stimulation index |
Median |
19.6 |
14.8 |
3.4 ** ## |
|
IQR |
14.9–74.5 |
6.2–35.3 |
1.4–13.7 |
|
|
Mφ (1x105 cells) were cultured with 1x106 allogeneic PBMCs over 5 days. 3[H]-thymidine (1 µCi/well) was added 18 h before harvesting to measure T-cell proliferation (cpm). The stimulation index is expressed in calculated units (cpm in MLC (PBMCs+Mφ) / cpm in control culture (PBMCs alone). |
||||
Generated Mφ differ in cytokine and chemokine production
To further characterize the secretory profile of generated Mφ subsets, we measured the production of Th1/pro-inflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-12, IL-17, IL-18, IL-6) and Th2/anti-inflammatory cytokines (IL-4, IL-10, IL-13). Cytokine levels were measured in supernatants of 7-day cultures of Mφ1, Mφ2 and Mφ3. Mφ1 spontaneously produced considerable levels of IL-1β, IL-6, TNF-α, IFN- γ, IL-4, and IL-17 (Table 3). This finding confirms the pro-inflammatory nature of Mφ1 and their capacity for T-cell activation. Mφ2 were characterized by lower secretory activity for some of these cytokines, though the differences were significant only for IL-4 and IL-18. In contrast, Mφ3 displayed remarkably decreased basal levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18), Th1-cytokines (IFN-γ, IL-2), and IL-4. Mφ3 also differed from Mφ1 by a 2-fold lower IL-12 production and more pronounced production of IL-10, though not significantly. In addition to cytokines, we measured the levels of various inflammatory chemokines in the supernatants of unstimulated macrophages. Generated Mφ constitutively produced high levels of IL-8, MCP-1, and MIP-1β. Mφ1 and Mφ2 demonstrated similar levels in their production. In contrast, secretion of neutrophil-attracting IL-8 and monocyte-attracting MCP-1 by Mφ3 was significantly lower than by Mφ1 and Mφ2. However, the production of T-cell attracting MIP-1β by Mφ3 did not differ from that by Mφ1 and Mφ2. Together, these data confirm the pro-inflammatory nature of Mφ1 and significantly less pro-inflammatory activity of Mφ3.
Table 3. Cytokine/chemokine concentrations secreted by Mφ1, Mφ2, and Mφ3
|
Cytokines& |
Mφ1 (n=10) Median |
IQR |
Mφ2(n=10) Median |
IQR |
Mφ3 (n=24) Median |
IQR |
|---|---|---|---|---|---|---|
|
|
872 |
734–995 |
839 |
539–1010 |
626 * ↓ |
440–830 |
|
IL-2 |
154 |
115–154 |
115 |
70–155 |
72 *↓ |
47–115 |
|
IL-1β |
405 |
246–670 |
313 |
150–790 |
195 * # ↓ |
68–290 |
|
TNF-α |
175 |
124–282 |
148 |
55–224 |
99 * ↓ |
51–156 |
|
IL-12 |
28 |
20–29 |
19 |
7–25 |
14 |
3–33 |
|
IL-17 |
308 |
245–483 |
257 |
177–448 |
214 |
112–427 |
|
IL-18 |
33 |
29–51 |
27 * ↓ |
16.5–31.2 |
19 * ↓ |
15.7–35.8 |
|
IL-6 |
21340 |
13430–27340 |
20350 |
8380–25060 |
10900 * ↓ |
4110–21770 |
|
IL-4 |
215 |
198–246 |
119 ** ↓ |
79–141 |
106 ** ↓ |
53–190 |
|
IL-10 |
5 |
2–10 |
2 |
2–2 |
15 |
2–60 |
|
IL-13 |
78 |
37–113 |
48 |
37–78 |
78 |
42–112 |
|
IL-8 |
90380 |
74280–93340 |
67400 |
57940–94430 |
44320 ** ## ↓ |
29150–59000 |
|
MCP-1 |
11140 |
5680–14000 |
11910 |
4160–17660 |
3345 ** ## ↓ |
1100–4460 |
|
MIP-1β |
1 960 |
1250–5590 |
1 560 |
930–2700 |
2220 |
790–7620 |
|
* pU < 0.05 and ** pU < 0.01 vs Mφ1; # pU < 0.05 and ## pU < 0.01 vs Mφ2. |
||||||
Production of growth factors by generated Mφ
All three types of unstimulated macrophages secreted detectable concentrations of erythropoietin, G-CSF, FGF-basic, BDNF, and IGF-1 (Table 4). Mφ1 and Mφ2 produced analogous levels of these growth factors, although there was a strong tendency to higher production of EPO by Mφ2. Despite the decreased production of pro-inflammatory cytokines, Mφ3 secreted concentrations of G-CSF, EPO, FGF-basic and EGF comparable with Mφ2, though significantly lower concentration of BDNF. But the most prominent difference was revealed for the production of IGF-1, which was much higher in Mφ3 in comparison with Mφ1 and Mφ2 cultures. Concerning VEGF, its detectable concentrations in 7-day cultures were determined only in a quarter of tested donors. Among these cultures VEGF was predominantly produced by Mφ2, and especially by Mφ-3, but not Mφ1.
Table 4. Growth factors production by Mφ1, Mφ2 and Mφ3
Growth factors (pg/ml) | Mφ1 (n=10) | IQR | Mφ2 (n=10) | IQR | Mφ3 (n=24) | IQR |
|---|---|---|---|---|---|---|
G-CSF | 670 | 505–1610 | 730 | 315–2310 | 430 | 180–1050 |
EPO | 19.2 | 1.7–36.9 | 46.5 | 33.8–81.1 | 34.9 | 21.5–56.5 |
FGF-basic | 104 | 57–124 | 150 | 87–180 | 109 | 45–126 |
EGF | 207 | 148–331 | 283 | 245–420 | 138 | 38–310 |
BDNF | 392 | 187–705 | 438 | 215–739 | 131 * # ↓ | 78–235 |
IGF-1 | 322 | 170–8560 | 152 | 116–459 | 8310 * ## ↑ | 520–9500 |
VEGF (n=6) | 5.0 | 5.0–97 | 92.8 * ↑ | 59.2–298 | 422.4 * # ↑ | 107.7–524.7 |
* pU < 0.05 and ** pU < 0.01 vs Mφ1; # pU < 0.05 and ## pU < 0.01 vs Mφ2. | ||||||
Discussion
Over the last decade, there has been an increasing interest in the role of the inflammatory reaction in CNS injury. Moreover, this interest has focused on the dominant cell type observed during inflammation, the macrophage. However, in the CNS the contribution of these cells to the healing process remains questionable [6].
The contradictory data regarding the contribution of Mφ to CNS recovery could be explained by diverse macrophage activities, many of which appear to be oppositional in nature. The destructive potential of macrophages in CNS pathology may be caused by pro-inflammatory activity, whereas their regenerative capacity may be linked with anti-inflammatory features [12].
In the search for macrophages with potential regenerative activity we developed a simple method for the generation of macrophages in growth factor deficient conditions and analyzed the phenotype and functional activity of these macrophages, termed Mφ3, with pro-inflammatory Mφ1 and anti-inflammatory Mφ2. We speculated that the deficiency of growth factors in low serum conditions may be one of the key factors capable of activating regenerative properties of macrophages. Particularly, low serum conditions during macrophage cultivation could stimulate deprivation-induced apoptosis of culturing cells (including admixture of non-adherent cells), and the ingestion of apoptotic cells may change the functional activity of macrophages toward an anti-inflammatory phenotype.
The received data demonstrated that low serum conditions did not influence the efficacy of Mφ3 generation. Moreover, the yield of Mφ3 significantly exceeded the number of Mφ1 and Mφ2. These data are correspondent with Plesner's study, who showed an enhanced yield of M-CSF treated macrophages in cultures with 1% fetal calf serum [22].
According to study of Verreck et al, anti-inflammatory Mφ2 have a lower expression of HLA-DR and CD86 molecules after LPS stimulation, though unstimulated macrophages expressed similar levels of these molecules [34]. We have shown that as compared to Mφ1 and Mφ2, Mφ3 cultures contained lower numbers of HLA-DR and CD86-positive cells. These differences, though not statistically significant, were important for the association with the decreased capacity of Mφ3 to stimulate allogeneic T cell proliferation. Type-2 anti-inflammatory macrophages are known to have a lower ability to stimulate T-cell proliferation in MLC [11]. This is in agreement with our data, and pointed to the lower allostimulatory activity of Mφ2 in comparison with Mφ1. Notably, Mφ3 virtually failed to stimulate lymphocyte proliferation in MLC. The medium value of the Mφ3 stimulation index was more than 6-fold lower than that of Mφ1. This fact strongly suggests that generated Mφ3 are not immunogenic and in this respect resemble anti-inflammatory M2 macrophages.
To further evaluate the pro- and anti-inflammatory activity of generated macrophages we compared their capacity to spontaneous production of Th1/pro- and Th2/anti-inflammatory cytokines. In contrast to Mφ1, Mφ3 produced significantly (2-fold) lower concentrations of pro-inflammatory (IL-1β, TNF-α, IL-6, IL-18) and Th1/Th2-cytokines (IFN-γ, IL-2, IL-4). Mφ3 supernatants also contained 2-fold lower concentrations of IL-12 and higher levels of IL-10, though these differences were not statistically significant.
Gordon and coworkers [11] have described alternatively activated macrophages after treatment with IL-4 or IL-13, which produce IL-10 without microbial stimulation. At the same time the study of Verreck demonstrated that unlike alternatively activated Mφ, M-CSF polarized Mφ2 failed to release IL-10 without activation, but effectively secreted IL-10 after mycobacterial activation. However, activated Mφ-2 produced no or relatively low levels of IL-12, IL-1β, IL-6, TNF-α [34]. We also did not reveal any significant concentrations of IL-10 in the supernatants of unstimulated Mφ2. In contrast to Mφ-2, Mφ-3 spontaneously produced IL-10 and displayed significantly less pro-inflammatory phenotype (as compare with Mφ1) without any additional stimulation.
Our results are also in agreement with findings suggesting a high ability of M-CSF polarized Mφ2 to secrete pro-inflammatory chemokines [35]. Mφ3 were also shown to secrete MIP-1β levels comparable with Mφ1 and Mφ2, but lower levels of IL-8 and MCP-1. This indicated that unlike Mφ1 and Mφ2 subsets, Mφ3 has less capacity to attract neutrophils and monocytes and therefore is less effective in supporting inflammation, whereas they could recruit effector Th1 cells and modify their functions.
One possible mechanism underlying the beneficial role of macrophages in CNS repair is connected with their capacity to produce a wide range of growth factors that can promote neuroprotection and regeneration [30, 17, 6]. The comparative analysis of some growth factors in the supernatants of generated macrophages revealed that all three Mφ subsets spontaneously produced detectable levels of EPO, G-CSF, IGF-1, FGF-basic, EGF, and BDNF. Mφ3 secreted concentrations of G-CSF, FGF-basic and EGF similar to Mφ1 and Mφ2, EPO comparable with Mφ2, and a lower level of BDNF, but more than 25-fold higher level of IGF-1. As for VEGF, this growth factor, identified only in quarter of patients, was produced by both Mφ2 and Mφ3, but not Mφ-1 and was significantly higher in Mφ3- than in Mφ2 cultures.
Production of classical neurotrophic factors including CNTF, IGF, HGF, PDGF, NGF, BDNF, GDNF, and NT-3 by macrophages have been shown in numerous studies [3, 7, 13]. Evaluation of two of these factors (BDNF and IGF-1) in cultures of distinct macrophage subtypes in our study supported previous data and demonstrated comparable production of these factors by inflammatory Mφ1 and anti-inflammatory Mφ2. Moreover we have shown for the first time that in spite of a lower level of BDNF, Mφ3 were characterized with exclusively high secretion of IGF-1.
IGF-1 is a potent neurotrophic factor. Its pleiotropic effects range from classical trophic actions on neurons such as housekeeping or anti-apoptotic/pro-survival effects to modulation of brain-barrier permeability, neuronal excitability, or new neuron formation. IGF-1 is also known to significantly improve axon growth and remyelination [2, 4]. The finding that IGF-1 is secreted abundantly by Mφ3 may point toward an important potential role for these macrophages in neuroprotection and regeneration.
In addition to neurotrophic factors, generated macrophages produced significant levels of VEGF. Detection of VEGF (in 7-day macrophage supernatants) only in part of the tested donors could be connected with an earlier peak of VEGF production. Nevertheless, in detectable cases VEGF was predominantly produced by both Mφ2 and Mφ3. VEGF has direct neuroprotective effects on motoneurons, induces neurogenesis and angiogenesis and its reduced levels cause neurodegeneration in part by impairing neural tissue perfusion [31, 38].
Other factors, such as EPO, G-CSF, FGF-β, and EGF, produced by Mφ-3 and Mφ1/Mφ2 subsets could also underlay the neuro-regenerative macrophage potential. Erythropoietin functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production. This cytokine promotes both neuroprotection and neuroregeneration in various models of CNS injury and disease and is considered to be a promising candidate as neuroprotective agent [29,15]. G-CSF appears to have anti-apoptotic effect and stimulate differentiation of adult neural stem cells [26]. EGF is a motility factor for microglial cells and is shown to enhance the differentiation, maturation and survival of a variety of neurons in the central nervous system [36]. FGF-basic promotes the survival and neurite growth of brain neurons in vitro and in vivo, suggesting that it functions as a neurotrophic factor. In addition FGF acutely modulates synaptic transmission in the hippocampus, suggesting that it has a role similar to a neurotransmitter or neuromodulator [1].
Several groups have confirmed the therapeutic potential of activated microglia and monocyte derived macrophages in the injured spinal cord [3, 23-25]. The success of these pre-clinical models prompted a Phase I clinical trial that was completed without any adverse effects. Implantation of macrophages preincubated with dermis was well tolerated. Of the eight patients with complete spinal cord injury, three recovered clinically significant neurological motor and sensory function [16].
Recent study of this group showed that augmenting the naive monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Notably, the enhancement of motor functions was associated with anti-inflammatory activity of infiltrating macrophages, mediated by interleukin 10 [28].
In this aspect, the Mφ3 subset described in our study is characterized by low pro-inflammatory/immunogenic properties and high regenerative potential and therefore may represent new candidates for cell therapy in CNS injuries.
Acknowledgements
The authors declare no competing interests.
References
1. Abe, K. Effects of basic fibroblast growth factor on central nervous system functions. Pharmacol Res. 2001;43:307-302.
2. Apel PJ, Ma J, Callahan M, Northam CN, Alton TB, Sonntag WE, Li Z. Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve. 2009 Oct. 2. doi: 10.1002/mus.21485.
3. Bomstein Y, Marder JB, Vitner K, Smirnov I, Lisaey G, Butovsky O, Fulga V, Yoles E. Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol. 2003;142:10-16. doi: 10.1016/S0165-5728(03)00260-1.
4. Carro E, Trejo JL, Núñez, A, Torres-Aleman I. Brain repair and neuroprotection by serum insulin-like growth factor-I. Mol Neurobiol. 2003;27:153-162. doi: 10.1385/MN:27:2:153.
5. Correale J, Villa A. The neuroprotective role of inflammation in nervous system injuries. J Neurol. 2004;251:1304-1316. doi: 10.1007/s00415-004-0649-z.
7. Elkabes S, Dicicco-Bloom EM, Black IB. Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci. 1996;16:2508-2521. pmid: 8786427.
9. Fitch MT, Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Exp Neurol. 1997;148:587-603. doi: 10.1006/exnr.1997.6701.
10. Gordon, S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3:23-35. doi:10.1038/nri978.
11. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 2005;5:953-964. doi: 10.1038/nri1733.
12. Hohlfeld R, Kerschensteiner M, Meinl E. Dual role of inflammation in CNS disease. Neurology. 2007;68(3):58-63. pmid: 17548571.
13. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WEF, Kolbeck R, Hoppe E, Oropeza-Wekerle R-L, Bartke L, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med. 1999;189:865-870.
15. King C.E, Rodger J, Bartlett C, Esmaili T, Dunlop SA, Beazley LD. Erythropoietin is both neuroprotective and neuroregenerative following optic nerve transaction. Exp Neurol. 2007;205:48-55.
16. Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, Marder JB, Yoles E, Belkin M, Schwartz M, Hadani M. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg. 2005;3:173-181.
18. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677-686. doi:10.1016/j.it.2004.09.015.
19. McPhail LT, Stirling DP, Tetzlaff W, Kwiecien JM, Ramer MS. The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury. Eur J Neurosci. 2004;20:1984-1994. doi: 10.1111/j.1460-9568.2004.03662.x.
20. Mosser DM. The many faces of macrophage activation. J Leukocyte Biol. 2003;73:209-212.
22. Plesner A, Greenbaumb CJ, Lernmarka A. Low serum conditions for in vitro generation of human macrophages with macrophage colony stimulating factor. J Immunol Meth. 2001;249:53–61.
23. Prewitt CM, Niesman IR, Kane CJ, Houle JD. Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol. 1997;148:433-443. doi:10.1006/exnr.1997.6694.
24. Rabchevsky AG, Streit WJ. Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res. 1997;47:34-48. doi: 10.1002/(SICI)1097-4547(19970101)47:1<34::AID-JNR4>3.0.CO;2-G.
25. Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 1998;4:814-821. pmid: 9662373.
27. Schwartz M, Lazarov-Spiegler O, Rapalino O, Agranov I, Velan G, Hadani M. Potential repair of rat spinal cord injuries using stimulated homologous macrophages. Neurosurgery. 1999;44:1041-1045. pmid: 10232537.
29. Spate CK, Krampe H, Ehrenreich H. Recombinant human erythropoietin: novel strategies for neuroprotective/neuroregenerative treatment of multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2008;1:193-206.
30. Stoll G, Jander S, Schroeter M. Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol. 2002;513:87-113. pmid: 12575818.
33. Turrin NP, Rivest S. Molecular and cellular immune mediators of neuroprotection. Molecular Neurobiology. 2006;34:221-242. doi: 10.1385/MN:34:3:221.
36. Wing R, Wong C, Guillaud L. The role of epidermal growth factor and its receptors in mammalian CNS. Cytokines & Growth factors. 2004;15:147-156.
38. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, van Bruggen N, Chopp M. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106:829-838.
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Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF. <br /><br />Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. 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["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18503" ["VALUE"]=> array(2) { ["TEXT"]=> string(229) "<p>Елена Р. Черных, Екатерина Я. Шевела, Людмила В. Сахно, Марина А. Тихонова, Ярослав Л. Петровский, Александр А. Останин</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(217) "Елена Р. Черных, Екатерина Я. Шевела, Людмила В. Сахно, Марина А. Тихонова, Ярослав Л. Петровский, Александр А. Останин
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18504" ["VALUE"]=> array(2) { ["TEXT"]=> string(3773) "<p class="bodytext">Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF. <br /><br />Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз. <br /><br />Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3727) "Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF.
Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз.
Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом.
Elena R. Chernykh, Ekaterina Ya. Shevela, Ludmila V. Sakhno, Marina A. Tikhonova, Yaroslav L. Petrovsky, Alexander A. Ostanin
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Correspondence
Elena Chernykh, Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology RAMS SB, Yadrintsevskaya str., 14, Novosibirsk, 630099, Russia
Phone: +7(383)2360329; Fax: +7(383)2227028; E-mail: ct_lab@mail.ru
Regulation of the immune response seems to be a promising strategy for a successful central nervous system (CNS) repair, and macrophages are considered to be prospective candidates for cell therapy. Using low serum conditions we generated human anti-inflammatory M2-like macrophages from peripheral blood monocytes and compared these cells (termed Mφ3) with “standard” pro-inflammatory Mφ1 and anti-inflammatory Mφ2, generated in the presence of GM-CSF and M-CSF. We focused primarily on the differences in T-cell stimulatory activity and production of various cytokines, chemokines, and growth factors. Low serum conditions had no negative impact on macrophage yield, the largest of which was for Mφ3. We showed that Mφ3 more closely resembled Mφ2 than Mφ1. Mφ2 and particularly Mφ3, but not Mφ1 expressed relatively low levels of CD86 and failed to stimulate T-cell proliferation. In contrast to pro-inflammatory Mφ1, unstimulated Mφ3 produced significantly lower levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18, IL-12) and Th1/Th2-cytokines (IFN-γ, IL-2, IL-4) coupled with a higher IL-10 level. Moreover, concentrations of IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in Mφ-3 supernatants were lower not only when compared to Mφ1, but also to Mφ2 cultures. Like Mφ1 and Mφ2, Mφ3 was capable of producing neurotrophic- (BDNF, IGF-1), angiogenic- (VEGF), and other growth factors (EPO, G-CSF, FGF-basic, EGF) with neuroprotective and regenerative activity. In fact, IGF-1 production by Mφ-3 exceeds secretion of this factor by Mφ-1 and Mφ-2 by more than 25 fold. Thus, generated Mφ-3 represented M2-like macrophages with high regenerative potential." 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Chernykh, Ekaterina Ya. Shevela, Ludmila V. Sakhno, Marina A. Tikhonova, Yaroslav L. Petrovsky, Alexander A. Ostanin</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(132) "
Elena R. Chernykh, Ekaterina Ya. Shevela, Ludmila V. Sakhno, Marina A. Tikhonova, Yaroslav L. Petrovsky, Alexander A. Ostanin
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Regulation of the immune response seems to be a promising strategy for a successful central nervous system (CNS) repair, and macrophages are considered to be prospective candidates for cell therapy. Using low serum conditions we generated human anti-inflammatory M2-like macrophages from peripheral blood monocytes and compared these cells (termed Mφ3) with “standard” pro-inflammatory Mφ1 and anti-inflammatory Mφ2, generated in the presence of GM-CSF and M-CSF. We focused primarily on the differences in T-cell stimulatory activity and production of various cytokines, chemokines, and growth factors. Low serum conditions had no negative impact on macrophage yield, the largest of which was for Mφ3. We showed that Mφ3 more closely resembled Mφ2 than Mφ1. Mφ2 and particularly Mφ3, but not Mφ1 expressed relatively low levels of CD86 and failed to stimulate T-cell proliferation. In contrast to pro-inflammatory Mφ1, unstimulated Mφ3 produced significantly lower levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18, IL-12) and Th1/Th2-cytokines (IFN-γ, IL-2, IL-4) coupled with a higher IL-10 level. Moreover, concentrations of IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in Mφ-3 supernatants were lower not only when compared to Mφ1, but also to Mφ2 cultures. Like Mφ1 and Mφ2, Mφ3 was capable of producing neurotrophic- (BDNF, IGF-1), angiogenic- (VEGF), and other growth factors (EPO, G-CSF, FGF-basic, EGF) with neuroprotective and regenerative activity. In fact, IGF-1 production by Mφ-3 exceeds secretion of this factor by Mφ-1 and Mφ-2 by more than 25 fold. 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Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology of Russian Academy of Medical Sciences, Siberian Branch, Novosibirsk, Russia
Correspondence
Elena Chernykh, Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology RAMS SB, Yadrintsevskaya str., 14, Novosibirsk, 630099, Russia
Phone: +7(383)2360329; Fax: +7(383)2227028; E-mail: ct_lab@mail.ru
Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology of Russian Academy of Medical Sciences, Siberian Branch, Novosibirsk, Russia
Correspondence
Elena Chernykh, Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology RAMS SB, Yadrintsevskaya str., 14, Novosibirsk, 630099, Russia
Phone: +7(383)2360329; Fax: +7(383)2227028; E-mail: ct_lab@mail.ru
Елена Р. Черных, Екатерина Я. Шевела, Людмила В. Сахно, Марина А. Тихонова, Ярослав Л. Петровский, Александр А. Останин
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"500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18504" ["VALUE"]=> array(2) { ["TEXT"]=> string(3773) "<p class="bodytext">Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF. <br /><br />Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз. <br /><br />Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3727) "Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF.
Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз.
Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом.
Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF.
Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз.
Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом.
Introduction
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for high risk hematological malignancies. Its success, however, is hampered by high treatment associated mortality, mostly due to acute and chronic graft versus host disease (GVHD).
Although mild chronic GVHD may improve survival in patients with malignant diseases and usually needs no therapeutic intervention, severe chronic GVHD has devastating effects on multiple organs and significantly contributes to late morbidity and mortality in long-term survivors after allogeneic HCT [1]. The only established treatment of chronic graft versus host disease is the use of high dose corticosteroids. This therapy, however, is associated with multiple adverse reactions including life threatening infections, and moreover not all patients respond to this treatment approach. Therefore alternative treatment options are urgently needed.
Calcineurin inhibitors
In 1988 Sullivan introduced a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) for patients with high-risk extensive chronic GVHD (thrombocytopenia < 100.000/µl) as primary treatment, and achieved with this approach a remarkable 4-year survival of 50%. The overall response rate after 9 months was 56%, and there were 17% treatment failures. The relapse risk was 23% and the mortality 47% [2]. These results were strikingly better when compared to an earlier study where using steroids alone for patients with these disease characteristics resulted in a 5-year survival of only 26% [3]. For many years the combination of cyclosporine and prednisolone was regarded as standard primary treatment of chronic GVHD [4]. However, a more recent large randomized clinical trial comparing the combination therapy with prednisolone monotherapy revealed no difference in the major endpoints therapy-related mortality, overall mortality, need for secondary treatment, or discontinuation of all immunosuppressive therapies. However, disease-free survival was significantly worse in the combination arm, suggesting a destructive effect of cyclosporine on the graft-versus-leukemia effect [5]. Although this study was performed in patients without thrombocytopenia, it nevertheless did not substantiate the hypothesis that the administration of cyclosporine reduces transplantation-related mortality among patients with chronic GVHD.
Another calcineurin inhibitor used in transplantation is tacrolimus. However, data on its use in chronic GVHD is scarce. Its efficacy as salvage therapy in chronic GVHD was evaluated in a small phase 2 study. Although 13% of patients achieved complete remission of GVHD and could discontinue tacrolimus, a failure rate of 79% is not very encouraging. Nevertheless, it might be of benefit in some selected patients [6].
Cytotoxic drugs (MTX, Cytoxan, Azathioprine, MMF, Pentostatin)
Since low-dose methotrexate (MTX) has been proven to be effective in the prophylaxis of acute GVHD and has low toxicity profile as well as being a cost effective alternative, it has been evaluated in a series of small retrospective analyses for the treatment of chronic GVHD [7-10]. The response rates varied from 59–76%, thus suggesting methotrexate in doses of 7.5 to 15 mg to be active in chronic GVHD. Best responses have been seen in lichenoid, cutaneous, and gastrointestinal chronic GVHD. Consequently, low-dose methotrexate should be evaluated in prospective clinical trials.
Another cytotoxic drug evaluated in a small patient series for the treatment of chronic GVHD is cytoxan. It was used as pulse therapy (1000 mg/m2) and the response was dependent on the organs involved, with best responses seen in skin and mucous membrane GVHD. Remarkably, 80% of patients with liver GVHD also responded to this treatment [11, 12].
The use of azathioprine in addition to prednisolone has been evaluated in a randomized trial in patients with chronic GVHD without thrombocytopenia [3]. No benefit could be observed by the addition of azathioprine. On the contrary, in the combination arm the non-relapse mortality doubled and overall survival decreased from 61% in the prednisolone arm to 47% in the prednisolone plus azathioprine arm. Therefore for treatment of chronic GVHD no role for azathioprine has been as yet established.
The more lymphocyte-selective purine antagonist mycophenolate mofetil (MMF) has been studied in a small prospective and several small retrospective studies for treatment of refractory chronic GVHD [13-15]. The response rates varied from 64-100% depending on organ involvement, with best responses seen in cutaneous manifestations. Generally the drug was well tolerated and a steroid sparing effect was observed in most studies. However, infectious complications seemed to be increased. A recent prospective randomized trial for initial treatment of chronic GVHD has been closed prematurely, as an interim analysis showed no benefit of adding MMF to standard treatment [16]. Therefore MMF should not be added to the initial systemic treatment regimen for chronic GVHD. Nevertheless MMF can be considered for secondary treatment of refractory patients.
Georgia Vogelsang has evaluated the purine analog pentostatin in a prospective phase 2 trial for treatment of steroid-resistant chronic GVHD [17]. Pentostatin was administered at a dosage of 4 mg/m2 every other week for a minimum of 24 weeks. Although most patients had failed more than one prior immunosuppressive regimen (median 4), 55% of the patients had an objective response and survival at 2 years was 70%. Responses were best in lichenoid skin GVHD. Of the 32 responders 8 went off the study because of adverse events. Infections were the most significant toxicity.
Thoraco-abdominal Irradiation
Low dose thoraco-abdominal irradiation (1 Gy) was applied by the group of the Hospital Saint-Louis in Paris to 41 patients with refractory extensive chronic GVHD [18]. Eighty-two percent of the patients achieved a clinical response, and two years after the irradiation 25% of the patients had a complete response. Best responses were seen in patients with fasciitis (79%) and oral GVHD lesions (73%). However, one third of the responders responded only temporarily. The major adverse event was mild pancytopenia. Especially in patients with fasciitis and oral GVHD lesions low dose thoraco-abdominal irradiation may be considered as a safe and efficient treatment option.
Immunomodulatory drugs
Thalidomide was first reported in 1992 to be active in chronic GVHD [19]. In the following years a couple of retrospective studies seemed to confirm its efficacy with response rates between 36 and 75% [20-22]. However, two randomized trials failed to prove any benefit of adding thalidomide to standard treatment of extensive chronic GVHD [23, 24]. The Seattle trial could not even evaluate the efficacy since more than 90% of the patients discontinued the study drug before resolution of GVHD, because of severe neutropenia and neurological symptoms. Therefore the use of thalidomide can not be generally recommended. However, selected patients may benefit from low dose thalidomide (100–200mg/d).
Clofazimine, a drug with activity in leprosy and various chronic autoimmune skin disorders, has been reported to be active also in chronic GVHD in a small phase 2 trial [25]. It was given orally once a day at a dose of 300 mg for 90 days and at a dose of 100 mg thereafter. More than 50% of the patients with skin involvement, contractures or oral GVHD manifestations achieved responses. The most common side effects were gastrointestinal and hyperpigmentation. Therefore clofazimine appears safe and, maybe, efficacious. However, the results of this small study are still to be confirmed in larger trials.
The malaria drug hydroxychloroquine is supposed to interfere with antigen presentation and has synergistic activity with calcineurin inhibitors in vitro. Therefore it has been evaluated for treatment of chronic GVHD in a small phase 2 trial [26]. Forty patients with steroid resistant or dependent chronic GVHD were treated with 12 mg/kg/day with an overall response rate of 53%. In all responders steroids could be tapered to at least 50% of the initial dosage. There were no major toxicities. While this study also awaits confirmation in larger trials, the use of hydroxychloroquine as prophylaxis for chronic GVHD revealed disappointing results in a randomized double blind clinical trial [27].
Cytokine modulation may be another treatment option to treat chronic GVHD. And, indeed, there have been anecdotal reports on the use of soluble tumor-necrosis-factor receptor [28, 29] or of antibodies against the interleukin-2 receptor [30, 31] for treatment of chronic GVHD. With patient numbers between 4 and 10 the response rates varied from 50% to 75%.
Two recent small clinical studies have suggested the tyrosine kinase inhibitor imatinib mesylate to be active in the treatment of steroid-refractory sclerodermatous GVHD, via inhibition of fibroblast activity and TGF-ß [32, 33]. Response rates of 50–79% have been reported. However, especially at higher doses, up to 30% of patients did not tolerate imatinib and stopped treatment.
Rituximab
As B-cells are involved in the pathophysiology of chronic GVHD via production of allo- and auto-antibodies it seems reasonable that the B-cell specific monoclonal antibody rituximab may be efficacious in the treatment of chronic GVHD. Several studies have addressed the role of rituximab in the treatment of chronic GVHD [34-37]. The overall response rates varied from 50–80%. Organ-specific response rates were 13 to 100% for involvement of the skin, 0 to 83% for involvement of the oral mucosa, 0 to 66% for involvement of the liver, and 0 to 38% for GVHD of the lung.
Extracorporal photopheresis (ECP)
In ECP a small part of the patient’s mononuclear cells are exposed to the photosensitizer 8-methoxypsoralen and irradiated with ultraviolet A light extra-corporally. The irradiated T-cells undergo apoptosis and the apoptotic cells are reinfused into the patient, and it has been suggested that secondarily tolerogenic antigen-presenting cells (APCs) are induced. Therefore ECP therapy, unlike other immunosuppressive regimens, does not cause global immunosuppression, but induces immune tolerance. Recent clinical and animal studies demonstrate that ECP therapy induces antigen-specific regulatory T cells, including CD4+CD25+FoxP3+ T cells and IL-10-producing Tr1 cells [38]. The clinical use of ECP to treat chronic GVHD was pioneered by Hildegard Greinix in Vienna [39]. In 15 patients ECP was well tolerated and achieved complete responses in 80 percent of cutaneous manifestations and 70% for liver involvement. Subsequently ECP was evaluated in a number of clinical trials [40-45]. In general, skin manifestations including sclerodermatous lesions responded best to ECP and occasionally it was also reported to improve pulmonary manifestations of chronic GVHD [46]. In a recent randomized multi-centre trial the addition of ECP to the standard treatment seemed to be more effective even in sclerodermatous skin disease with a 40% response rate at 12 treatment weeks, although the primary endpoint, blinded assessment of skin score, did not reach a significant level [47] However, a clear steroid sparing effect could be demonstrated.
Inhibitors of the mammalian target of rapamycin (mTOR-I)
Sirolimus and everolimus, inhibitors of the mammalian target of rapamycin (mTOR-I), combine immunosuppressive properties with antiproliferative effects on fibroblasts and smooth muscle cells [48]. mTOR-I exert their action by binding to FK-binding protein 12 (FKBP12), and subsequently forming a complex with the mammalian target of rapamycin (mTOR) and the raptor/rictor proteins. The generation of this complex results in cell cycle arrest in G1 via inhibition of DNA transcription, DNA translation, and protein synthesis. In contrast to CNI, sirolimus promotes the generation of CD4+CD25+FoxP3+ regulatory T-cells [49]. These data indicate that mTOR-I could provide additional advantage for the treatment of chronic GvHD both because of their antifibrotic activity and by possibly inducing tolerance. The mTOR-I sirolimus and everolimus have been extensively studied as immunosuppressants in solid organ transplantation. Substituting CNI with mTOR-I seems to overcome long term threats, like chronic allograft dysfunction and vasculopathy after solid organ transplantation [50]. In allogeneic hematopoietic cell transplantation, mTOR-I have demonstrated efficacy in prophylaxis and treatment of acute GVHD in a number of studies [51, 52].
However, considerable toxicity like transplant associated microangiopathy has been observed when mTOR-I were used in combination with CNI, which could be avoided in a CNI-free regimen [53]. Sirolimus has also been evaluated in second line treatment of chronic GVHD in small phase 2 trials mostly in combination with CNI [54-56]. The response rates varied between 56% and 81%. Major adverse events were hyperlipidemia, renal dysfunction, cytopenias and transplant-associated microangiopathy, which lead to termination of therapy in up to 1/3rd of treated patients. These experiences prompted us to avoid the combination of CNI and mTOR-I in the treatment of chronic GVHD. Intriguingly, when analyzing our data on the use of mTOR-I in sclerodermatous chronic GVHD, similar efficacy was achieved despite the absence of calcineurin-inhibitors (CNI). Compared with a study describing the treatment of chronic GVHD with sirolimus in combination with tacrolimus and corticosteroids we achieved similar response rates (76% in our study vs. 73% reported by Couriel et al.) and a more favorable toxicity profile [57]. Importantly, in contrast to the use of CNI, no increased relapse rate has been observed. This suggests that the graft versus leukemia effect is not compromised by mTOR-I therapy but may be even facilitated by the antitumoral activity of mTOR-I [58]. No differences were seen between sirolimus or everolimus treated patients. Importantly, in our study, we observed no nephrotoxicity and TMA was rare (5.9%), correlating with high trough levels of mTOR-I. Generally, if low therapeutic trough levels (4–8 ng/ml) were maintained, toxicities associated with mTOR-I therapy were moderate. Since mTOR-I possibly interfere with wound healing [59], they should be used with caution in patients with cutaneous or mucosal ulcers. In case of progressive ulcerous lesions, other therapeutic modalities should be chosen (e.g. extracorporal photopheresis). mTOR-I seem to enhance plasmatic coagulation, as suggested by significant shortening of prothrombin time in a significant number of patients. Therefore, plasmatic hemostasis markers should be monitored during mTOR-I therapy and antithrombotic prophylaxis should be considered, especially if patients have additional risk factors, e.g. steroid therapy. The involvement of mTOR in coagulation signaling cascades has as yet not been reported. Thus, further experimental studies are needed to clarify the possible role of mTOR-dependent downstream pathways in hemostasis. Hyperlipidemia was frequent, but seldom required therapeutic intervention. Similar results were observed in another CNI-free trial for the treatment of chronic GVHD utilizing everolimus in combination with steroids and in part with azathioprine [60]. Taken together mTOR-I appear to be an effective treatment option for chronic GVHD with a low toxicity profile as long as low therapeutic drug trough levels are maintained and combination treatment with CNI is avoided.
Conclusion
Severe chronic graft versus host disease remains the main factor for late morbidity and mortality in long-term survivors after allogeneic hematopoietic cell transplantation. The only established treatment of chronic graft versus host disease is the use of high dose corticosteroids, which is associated with multiple adverse reactions. Despite a myriad of alternative or additive treatment options up to date no clear strategy to treat chronic GVHD has been established. A better understanding of the pathophysiology of chronic GVHD may guide us in the future to a more sophisticated treatment strategy. Moreover, current available treatment options have to be evaluated in controlled prospective clinical trials. The NIH consensus of diagnosis and staging of chronic GVHD provides the tools for standardized evaluation of different treatment strategies. Most currently available treatment options rely on intensification of immunosuppression at the cost of a higher infection and possibly also a higher relapse rate. However, treatment options focusing on the induction of tolerance have emerged in recent years. While preserving the graft versus leukemia effect, both the use of ECP and the introduction of mTOR-I in the therapy of chronic GVHD have been associated with enhanced formation of regulatory T-cells, thus indicating a tolerance inducing effect.
It seems to be the time to shift the paradigm of treating chronic GVHD from mere immunosuppression to more sophisticated strategies.
References
4. Vogelsang GB. How I treat chronic graft-versus-host disease. Blood. 2001;97(5):1196-1201.
11. Mayer J, Krejci M, Pospisil Z, Doubek M, Janikova A, Zackova D, Racil Z, Smardova L, Navratil M, Kamelander J. Successful treatment of steroid-refractory hepatitic variant of liver graft-vs-host disease with pulse cyclophosphamide. Exp Hematol. 2009;37(6):767-73. pmid: 19463776.
13. Takami A, Mochizuki K, Okumura H, Ito S, Suga Y, Yamazaki H, Yamazaki M, Kondo Y, Asakura H, Nakao S. Mycophenolate mofetil is effective and well tolerated in the treatment of refractory acute and chronic graft-versus-host disease. Int J Hematol. 2006;83(1):80-5. pmid: 16443558.
14. Krejci M, Doubek M, Buchler T, Brychtova Y, Vorlicek J, Mayer J. Mycophenolate mofetil for the treatment of acute and chronic steroid-refractory graft-versus-host disease. Ann Hematol. 2005;84(10):681-5. doi: 10.1007/s00277-005-1070-0.
18. Robin M, Guardiola P, Girinsky T, Hernandez G, Esperou H, Ribaud P, et al. Low-dose thoracoabdominal irradiation for the treatment of refractory chronic graft-versus-host disease. Transplantation. 2005;80(5):634-642. pmid: 16177638.
19. Vogelsang GB, Farmer ER, Hess AD, Altamonte V, Beschorner WE, Jabs DA, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992;326(16):1055-1058. pmid: 1549151.
21. Kulkarni S, Powles R, Sirohi B, Treleaven J, Saso R, Horton C, Atra A, Ortin M, Rudin C, Goyal S, Sankpal S, Meller S, Pinkerton CR, Mehta J, Singhal S. Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease. Bone Marrow Transplant. 2003;32(2):165-70.
22. van de Poel MH, Pasman PC, Schouten HC. The use of thalidomide in chronic refractory graft versus host disease. Neth J Med. 2001;59(2):45-9. doi: 10.1016/S0300-2977(01)00133-4.
26. Gilman AL, Chan KW, Mogul A, Morris C, Goldman FD, Boyer M, et al. Hydroxychloroquine for the treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2000;6(3A):327-334. pmid: 10905770.
29. Chiang KY, Abhyankar S, Bridges K, Godder K, Henslee-Downey JP. Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease. Transplantation. 2002 Feb 27;73(4):665-7. pmid: 11889452.
37. von Bonin M, Oelschlägel U, Radke J, Stewart M, Ehninger G, Bornhauser M, Platzbecker U. Treatment of chronic steroid-refractory graft-versus-host disease with low-dose rituximab. Transplantation. 2008;86(6):875-9. pmid: 18813113.
38. Xia CQ, Campbell KA, Clare-Salzler MJ. Extracorporeal photopheresis-induced immune tolerance: a focus on modulation of antigen-presenting cells and induction of regulatory T cells by apoptotic cells.Curr Opin Organ Transplant. 2009;14(4):338-43.
41. Bisaccia E, Palangio M, Gonzalez J, Adler KR, Rowley SD, Goldberg SL. Treating refractory chronic graft-versus-host disease with extracorporeal photochemotherapy. Bone Marrow Transplant. 2003;31(4):291-4. doi: 10.1038/sj.bmt.1703830.
42. Ilhan O, Arat M, Arslan O, Ayyildiz E, Sanli H, Beksac M, Ozcan M, Gürman G, Akan H. Extracorporeal photoimmunotherapy for the treatment of steroid refractory progressive chronic graft-versus-host disease. Transfus Apher Sci. 2004;30(3):185-7. doi: 10.1016/j.transci.2004.02.003.
43. Foss FM, DiVenuti GM, Chin K, Sprague K, Grodman H, Klein A, Chan G, Stiffler K, Miller KB. Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: analysis of response and survival incorporating prognostic factors. Bone Marrow Transplant. 2005;35(12):1187-93. doi: 10.1038/sj.bmt.1704984.
44. Rubegni P, Cuccia A, Sbano P, Cevenini G, Carcagnì MR, D'Ascenzo G, De Aloe G, Guidi S, Guglielmelli P, Marotta G, Lauria F, Bosi A, Fimiani M. Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease. Br J Haematol. 2005;130(2):271-5.
45. Couriel DR, Hosing C, Saliba R, Shpall EJ, Anderlini P, Rhodes B, Smith V, Khouri I, Giralt S, de Lima M, Hsu Y, Ghosh S, Neumann J, Andersson B, Qazilbash M, Hymes S, Kim S, Champlin R, Donato M. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood. 2006;107(8):3074-80. doi: 10.1182/blood-2005-09-3907.
48. Kirken RA, Wang YL. Molecular actions of sirolimus: sirolimus and mTor. Transplant. Proc. 2003;35:227S-230S. pmid: 12742500.
50. Chapman JR, Valantine H, Albanell J, Arns WA, Campistol JM, Eisen H, Frigerio M, Lehmkuhl H, Marcen R, Morris R, Nashan B, Pascual J, Pohanka E, Segovia J, Zuckermann A. Proliferation signal inhibitors in transplantation: questions at the cutting edge of everolimus therapy. Transplant Proc. 2007;39(10):2937-50. doi: 10.1016/j.transproceed.2007.09.008.
52. Benito AI, Furlong T, Martin PJ, Anasetti C, Appelbaum FR, Doney K, et al. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72:1924-1929. pmid: 11773890.
53. Schleuning M, Judith D, Jedlickova Z, Stübig T, Heshmat M, Baurmann H, Schwerdtfeger R. Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in allo-SCT for leukemia patients with high relapse risk: an observational cohort study. Bone Marrow Transplant. 2009;43:717-723. doi: 10.1038/bmt.2008.377.
57. Jedlickova Z, Burlakova I, Cook A, Baurmann H, Schwerdtfeger R, Schleuning M. mTOR inhibitors for treatment of sclerodermatous chronic graft-versus-host disease following allogeneic stem cell transplantation. Bone Marrow Transplant. 2009;43(suppl. 1):S123(abs.).
59. Kuppahally S, Al-Khaldi A, Weisshaar D, et al. Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients. Am.J.Transplant. 2006;6:986-992.
60. Klink A, Schilling K, Rapp K, Höffken K, Sayer HG. High overall response rate in calcineurin inhibitor-free treatment with the mTOR inhibitor everolimus in advanced extensive chronic GvHD after allogeneic stem cell transplantation. Blood. 2008;112:2210 (abs.).
" ["~DETAIL_TEXT"]=> string(42550) "Introduction
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for high risk hematological malignancies. Its success, however, is hampered by high treatment associated mortality, mostly due to acute and chronic graft versus host disease (GVHD).
Although mild chronic GVHD may improve survival in patients with malignant diseases and usually needs no therapeutic intervention, severe chronic GVHD has devastating effects on multiple organs and significantly contributes to late morbidity and mortality in long-term survivors after allogeneic HCT [1]. The only established treatment of chronic graft versus host disease is the use of high dose corticosteroids. This therapy, however, is associated with multiple adverse reactions including life threatening infections, and moreover not all patients respond to this treatment approach. Therefore alternative treatment options are urgently needed.
Calcineurin inhibitors
In 1988 Sullivan introduced a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) for patients with high-risk extensive chronic GVHD (thrombocytopenia < 100.000/µl) as primary treatment, and achieved with this approach a remarkable 4-year survival of 50%. The overall response rate after 9 months was 56%, and there were 17% treatment failures. The relapse risk was 23% and the mortality 47% [2]. These results were strikingly better when compared to an earlier study where using steroids alone for patients with these disease characteristics resulted in a 5-year survival of only 26% [3]. For many years the combination of cyclosporine and prednisolone was regarded as standard primary treatment of chronic GVHD [4]. However, a more recent large randomized clinical trial comparing the combination therapy with prednisolone monotherapy revealed no difference in the major endpoints therapy-related mortality, overall mortality, need for secondary treatment, or discontinuation of all immunosuppressive therapies. However, disease-free survival was significantly worse in the combination arm, suggesting a destructive effect of cyclosporine on the graft-versus-leukemia effect [5]. Although this study was performed in patients without thrombocytopenia, it nevertheless did not substantiate the hypothesis that the administration of cyclosporine reduces transplantation-related mortality among patients with chronic GVHD.
Another calcineurin inhibitor used in transplantation is tacrolimus. However, data on its use in chronic GVHD is scarce. Its efficacy as salvage therapy in chronic GVHD was evaluated in a small phase 2 study. Although 13% of patients achieved complete remission of GVHD and could discontinue tacrolimus, a failure rate of 79% is not very encouraging. Nevertheless, it might be of benefit in some selected patients [6].
Cytotoxic drugs (MTX, Cytoxan, Azathioprine, MMF, Pentostatin)
Since low-dose methotrexate (MTX) has been proven to be effective in the prophylaxis of acute GVHD and has low toxicity profile as well as being a cost effective alternative, it has been evaluated in a series of small retrospective analyses for the treatment of chronic GVHD [7-10]. The response rates varied from 59–76%, thus suggesting methotrexate in doses of 7.5 to 15 mg to be active in chronic GVHD. Best responses have been seen in lichenoid, cutaneous, and gastrointestinal chronic GVHD. Consequently, low-dose methotrexate should be evaluated in prospective clinical trials.
Another cytotoxic drug evaluated in a small patient series for the treatment of chronic GVHD is cytoxan. It was used as pulse therapy (1000 mg/m2) and the response was dependent on the organs involved, with best responses seen in skin and mucous membrane GVHD. Remarkably, 80% of patients with liver GVHD also responded to this treatment [11, 12].
The use of azathioprine in addition to prednisolone has been evaluated in a randomized trial in patients with chronic GVHD without thrombocytopenia [3]. No benefit could be observed by the addition of azathioprine. On the contrary, in the combination arm the non-relapse mortality doubled and overall survival decreased from 61% in the prednisolone arm to 47% in the prednisolone plus azathioprine arm. Therefore for treatment of chronic GVHD no role for azathioprine has been as yet established.
The more lymphocyte-selective purine antagonist mycophenolate mofetil (MMF) has been studied in a small prospective and several small retrospective studies for treatment of refractory chronic GVHD [13-15]. The response rates varied from 64-100% depending on organ involvement, with best responses seen in cutaneous manifestations. Generally the drug was well tolerated and a steroid sparing effect was observed in most studies. However, infectious complications seemed to be increased. A recent prospective randomized trial for initial treatment of chronic GVHD has been closed prematurely, as an interim analysis showed no benefit of adding MMF to standard treatment [16]. Therefore MMF should not be added to the initial systemic treatment regimen for chronic GVHD. Nevertheless MMF can be considered for secondary treatment of refractory patients.
Georgia Vogelsang has evaluated the purine analog pentostatin in a prospective phase 2 trial for treatment of steroid-resistant chronic GVHD [17]. Pentostatin was administered at a dosage of 4 mg/m2 every other week for a minimum of 24 weeks. Although most patients had failed more than one prior immunosuppressive regimen (median 4), 55% of the patients had an objective response and survival at 2 years was 70%. Responses were best in lichenoid skin GVHD. Of the 32 responders 8 went off the study because of adverse events. Infections were the most significant toxicity.
Thoraco-abdominal Irradiation
Low dose thoraco-abdominal irradiation (1 Gy) was applied by the group of the Hospital Saint-Louis in Paris to 41 patients with refractory extensive chronic GVHD [18]. Eighty-two percent of the patients achieved a clinical response, and two years after the irradiation 25% of the patients had a complete response. Best responses were seen in patients with fasciitis (79%) and oral GVHD lesions (73%). However, one third of the responders responded only temporarily. The major adverse event was mild pancytopenia. Especially in patients with fasciitis and oral GVHD lesions low dose thoraco-abdominal irradiation may be considered as a safe and efficient treatment option.
Immunomodulatory drugs
Thalidomide was first reported in 1992 to be active in chronic GVHD [19]. In the following years a couple of retrospective studies seemed to confirm its efficacy with response rates between 36 and 75% [20-22]. However, two randomized trials failed to prove any benefit of adding thalidomide to standard treatment of extensive chronic GVHD [23, 24]. The Seattle trial could not even evaluate the efficacy since more than 90% of the patients discontinued the study drug before resolution of GVHD, because of severe neutropenia and neurological symptoms. Therefore the use of thalidomide can not be generally recommended. However, selected patients may benefit from low dose thalidomide (100–200mg/d).
Clofazimine, a drug with activity in leprosy and various chronic autoimmune skin disorders, has been reported to be active also in chronic GVHD in a small phase 2 trial [25]. It was given orally once a day at a dose of 300 mg for 90 days and at a dose of 100 mg thereafter. More than 50% of the patients with skin involvement, contractures or oral GVHD manifestations achieved responses. The most common side effects were gastrointestinal and hyperpigmentation. Therefore clofazimine appears safe and, maybe, efficacious. However, the results of this small study are still to be confirmed in larger trials.
The malaria drug hydroxychloroquine is supposed to interfere with antigen presentation and has synergistic activity with calcineurin inhibitors in vitro. Therefore it has been evaluated for treatment of chronic GVHD in a small phase 2 trial [26]. Forty patients with steroid resistant or dependent chronic GVHD were treated with 12 mg/kg/day with an overall response rate of 53%. In all responders steroids could be tapered to at least 50% of the initial dosage. There were no major toxicities. While this study also awaits confirmation in larger trials, the use of hydroxychloroquine as prophylaxis for chronic GVHD revealed disappointing results in a randomized double blind clinical trial [27].
Cytokine modulation may be another treatment option to treat chronic GVHD. And, indeed, there have been anecdotal reports on the use of soluble tumor-necrosis-factor receptor [28, 29] or of antibodies against the interleukin-2 receptor [30, 31] for treatment of chronic GVHD. With patient numbers between 4 and 10 the response rates varied from 50% to 75%.
Two recent small clinical studies have suggested the tyrosine kinase inhibitor imatinib mesylate to be active in the treatment of steroid-refractory sclerodermatous GVHD, via inhibition of fibroblast activity and TGF-ß [32, 33]. Response rates of 50–79% have been reported. However, especially at higher doses, up to 30% of patients did not tolerate imatinib and stopped treatment.
Rituximab
As B-cells are involved in the pathophysiology of chronic GVHD via production of allo- and auto-antibodies it seems reasonable that the B-cell specific monoclonal antibody rituximab may be efficacious in the treatment of chronic GVHD. Several studies have addressed the role of rituximab in the treatment of chronic GVHD [34-37]. The overall response rates varied from 50–80%. Organ-specific response rates were 13 to 100% for involvement of the skin, 0 to 83% for involvement of the oral mucosa, 0 to 66% for involvement of the liver, and 0 to 38% for GVHD of the lung.
Extracorporal photopheresis (ECP)
In ECP a small part of the patient’s mononuclear cells are exposed to the photosensitizer 8-methoxypsoralen and irradiated with ultraviolet A light extra-corporally. The irradiated T-cells undergo apoptosis and the apoptotic cells are reinfused into the patient, and it has been suggested that secondarily tolerogenic antigen-presenting cells (APCs) are induced. Therefore ECP therapy, unlike other immunosuppressive regimens, does not cause global immunosuppression, but induces immune tolerance. Recent clinical and animal studies demonstrate that ECP therapy induces antigen-specific regulatory T cells, including CD4+CD25+FoxP3+ T cells and IL-10-producing Tr1 cells [38]. The clinical use of ECP to treat chronic GVHD was pioneered by Hildegard Greinix in Vienna [39]. In 15 patients ECP was well tolerated and achieved complete responses in 80 percent of cutaneous manifestations and 70% for liver involvement. Subsequently ECP was evaluated in a number of clinical trials [40-45]. In general, skin manifestations including sclerodermatous lesions responded best to ECP and occasionally it was also reported to improve pulmonary manifestations of chronic GVHD [46]. In a recent randomized multi-centre trial the addition of ECP to the standard treatment seemed to be more effective even in sclerodermatous skin disease with a 40% response rate at 12 treatment weeks, although the primary endpoint, blinded assessment of skin score, did not reach a significant level [47] However, a clear steroid sparing effect could be demonstrated.
Inhibitors of the mammalian target of rapamycin (mTOR-I)
Sirolimus and everolimus, inhibitors of the mammalian target of rapamycin (mTOR-I), combine immunosuppressive properties with antiproliferative effects on fibroblasts and smooth muscle cells [48]. mTOR-I exert their action by binding to FK-binding protein 12 (FKBP12), and subsequently forming a complex with the mammalian target of rapamycin (mTOR) and the raptor/rictor proteins. The generation of this complex results in cell cycle arrest in G1 via inhibition of DNA transcription, DNA translation, and protein synthesis. In contrast to CNI, sirolimus promotes the generation of CD4+CD25+FoxP3+ regulatory T-cells [49]. These data indicate that mTOR-I could provide additional advantage for the treatment of chronic GvHD both because of their antifibrotic activity and by possibly inducing tolerance. The mTOR-I sirolimus and everolimus have been extensively studied as immunosuppressants in solid organ transplantation. Substituting CNI with mTOR-I seems to overcome long term threats, like chronic allograft dysfunction and vasculopathy after solid organ transplantation [50]. In allogeneic hematopoietic cell transplantation, mTOR-I have demonstrated efficacy in prophylaxis and treatment of acute GVHD in a number of studies [51, 52].
However, considerable toxicity like transplant associated microangiopathy has been observed when mTOR-I were used in combination with CNI, which could be avoided in a CNI-free regimen [53]. Sirolimus has also been evaluated in second line treatment of chronic GVHD in small phase 2 trials mostly in combination with CNI [54-56]. The response rates varied between 56% and 81%. Major adverse events were hyperlipidemia, renal dysfunction, cytopenias and transplant-associated microangiopathy, which lead to termination of therapy in up to 1/3rd of treated patients. These experiences prompted us to avoid the combination of CNI and mTOR-I in the treatment of chronic GVHD. Intriguingly, when analyzing our data on the use of mTOR-I in sclerodermatous chronic GVHD, similar efficacy was achieved despite the absence of calcineurin-inhibitors (CNI). Compared with a study describing the treatment of chronic GVHD with sirolimus in combination with tacrolimus and corticosteroids we achieved similar response rates (76% in our study vs. 73% reported by Couriel et al.) and a more favorable toxicity profile [57]. Importantly, in contrast to the use of CNI, no increased relapse rate has been observed. This suggests that the graft versus leukemia effect is not compromised by mTOR-I therapy but may be even facilitated by the antitumoral activity of mTOR-I [58]. No differences were seen between sirolimus or everolimus treated patients. Importantly, in our study, we observed no nephrotoxicity and TMA was rare (5.9%), correlating with high trough levels of mTOR-I. Generally, if low therapeutic trough levels (4–8 ng/ml) were maintained, toxicities associated with mTOR-I therapy were moderate. Since mTOR-I possibly interfere with wound healing [59], they should be used with caution in patients with cutaneous or mucosal ulcers. In case of progressive ulcerous lesions, other therapeutic modalities should be chosen (e.g. extracorporal photopheresis). mTOR-I seem to enhance plasmatic coagulation, as suggested by significant shortening of prothrombin time in a significant number of patients. Therefore, plasmatic hemostasis markers should be monitored during mTOR-I therapy and antithrombotic prophylaxis should be considered, especially if patients have additional risk factors, e.g. steroid therapy. The involvement of mTOR in coagulation signaling cascades has as yet not been reported. Thus, further experimental studies are needed to clarify the possible role of mTOR-dependent downstream pathways in hemostasis. Hyperlipidemia was frequent, but seldom required therapeutic intervention. Similar results were observed in another CNI-free trial for the treatment of chronic GVHD utilizing everolimus in combination with steroids and in part with azathioprine [60]. Taken together mTOR-I appear to be an effective treatment option for chronic GVHD with a low toxicity profile as long as low therapeutic drug trough levels are maintained and combination treatment with CNI is avoided.
Conclusion
Severe chronic graft versus host disease remains the main factor for late morbidity and mortality in long-term survivors after allogeneic hematopoietic cell transplantation. The only established treatment of chronic graft versus host disease is the use of high dose corticosteroids, which is associated with multiple adverse reactions. Despite a myriad of alternative or additive treatment options up to date no clear strategy to treat chronic GVHD has been established. A better understanding of the pathophysiology of chronic GVHD may guide us in the future to a more sophisticated treatment strategy. Moreover, current available treatment options have to be evaluated in controlled prospective clinical trials. The NIH consensus of diagnosis and staging of chronic GVHD provides the tools for standardized evaluation of different treatment strategies. Most currently available treatment options rely on intensification of immunosuppression at the cost of a higher infection and possibly also a higher relapse rate. However, treatment options focusing on the induction of tolerance have emerged in recent years. While preserving the graft versus leukemia effect, both the use of ECP and the introduction of mTOR-I in the therapy of chronic GVHD have been associated with enhanced formation of regulatory T-cells, thus indicating a tolerance inducing effect.
It seems to be the time to shift the paradigm of treating chronic GVHD from mere immunosuppression to more sophisticated strategies.
References
4. Vogelsang GB. How I treat chronic graft-versus-host disease. Blood. 2001;97(5):1196-1201.
11. Mayer J, Krejci M, Pospisil Z, Doubek M, Janikova A, Zackova D, Racil Z, Smardova L, Navratil M, Kamelander J. Successful treatment of steroid-refractory hepatitic variant of liver graft-vs-host disease with pulse cyclophosphamide. Exp Hematol. 2009;37(6):767-73. pmid: 19463776.
13. Takami A, Mochizuki K, Okumura H, Ito S, Suga Y, Yamazaki H, Yamazaki M, Kondo Y, Asakura H, Nakao S. Mycophenolate mofetil is effective and well tolerated in the treatment of refractory acute and chronic graft-versus-host disease. Int J Hematol. 2006;83(1):80-5. pmid: 16443558.
14. Krejci M, Doubek M, Buchler T, Brychtova Y, Vorlicek J, Mayer J. Mycophenolate mofetil for the treatment of acute and chronic steroid-refractory graft-versus-host disease. Ann Hematol. 2005;84(10):681-5. doi: 10.1007/s00277-005-1070-0.
18. Robin M, Guardiola P, Girinsky T, Hernandez G, Esperou H, Ribaud P, et al. Low-dose thoracoabdominal irradiation for the treatment of refractory chronic graft-versus-host disease. Transplantation. 2005;80(5):634-642. pmid: 16177638.
19. Vogelsang GB, Farmer ER, Hess AD, Altamonte V, Beschorner WE, Jabs DA, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992;326(16):1055-1058. pmid: 1549151.
21. Kulkarni S, Powles R, Sirohi B, Treleaven J, Saso R, Horton C, Atra A, Ortin M, Rudin C, Goyal S, Sankpal S, Meller S, Pinkerton CR, Mehta J, Singhal S. Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease. Bone Marrow Transplant. 2003;32(2):165-70.
22. van de Poel MH, Pasman PC, Schouten HC. The use of thalidomide in chronic refractory graft versus host disease. Neth J Med. 2001;59(2):45-9. doi: 10.1016/S0300-2977(01)00133-4.
26. Gilman AL, Chan KW, Mogul A, Morris C, Goldman FD, Boyer M, et al. Hydroxychloroquine for the treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2000;6(3A):327-334. pmid: 10905770.
29. Chiang KY, Abhyankar S, Bridges K, Godder K, Henslee-Downey JP. Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease. Transplantation. 2002 Feb 27;73(4):665-7. pmid: 11889452.
37. von Bonin M, Oelschlägel U, Radke J, Stewart M, Ehninger G, Bornhauser M, Platzbecker U. Treatment of chronic steroid-refractory graft-versus-host disease with low-dose rituximab. Transplantation. 2008;86(6):875-9. pmid: 18813113.
38. Xia CQ, Campbell KA, Clare-Salzler MJ. Extracorporeal photopheresis-induced immune tolerance: a focus on modulation of antigen-presenting cells and induction of regulatory T cells by apoptotic cells.Curr Opin Organ Transplant. 2009;14(4):338-43.
41. Bisaccia E, Palangio M, Gonzalez J, Adler KR, Rowley SD, Goldberg SL. Treating refractory chronic graft-versus-host disease with extracorporeal photochemotherapy. Bone Marrow Transplant. 2003;31(4):291-4. doi: 10.1038/sj.bmt.1703830.
42. Ilhan O, Arat M, Arslan O, Ayyildiz E, Sanli H, Beksac M, Ozcan M, Gürman G, Akan H. Extracorporeal photoimmunotherapy for the treatment of steroid refractory progressive chronic graft-versus-host disease. Transfus Apher Sci. 2004;30(3):185-7. doi: 10.1016/j.transci.2004.02.003.
43. Foss FM, DiVenuti GM, Chin K, Sprague K, Grodman H, Klein A, Chan G, Stiffler K, Miller KB. Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: analysis of response and survival incorporating prognostic factors. Bone Marrow Transplant. 2005;35(12):1187-93. doi: 10.1038/sj.bmt.1704984.
44. Rubegni P, Cuccia A, Sbano P, Cevenini G, Carcagnì MR, D'Ascenzo G, De Aloe G, Guidi S, Guglielmelli P, Marotta G, Lauria F, Bosi A, Fimiani M. Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease. Br J Haematol. 2005;130(2):271-5.
45. Couriel DR, Hosing C, Saliba R, Shpall EJ, Anderlini P, Rhodes B, Smith V, Khouri I, Giralt S, de Lima M, Hsu Y, Ghosh S, Neumann J, Andersson B, Qazilbash M, Hymes S, Kim S, Champlin R, Donato M. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood. 2006;107(8):3074-80. doi: 10.1182/blood-2005-09-3907.
48. Kirken RA, Wang YL. Molecular actions of sirolimus: sirolimus and mTor. Transplant. Proc. 2003;35:227S-230S. pmid: 12742500.
50. Chapman JR, Valantine H, Albanell J, Arns WA, Campistol JM, Eisen H, Frigerio M, Lehmkuhl H, Marcen R, Morris R, Nashan B, Pascual J, Pohanka E, Segovia J, Zuckermann A. Proliferation signal inhibitors in transplantation: questions at the cutting edge of everolimus therapy. Transplant Proc. 2007;39(10):2937-50. doi: 10.1016/j.transproceed.2007.09.008.
52. Benito AI, Furlong T, Martin PJ, Anasetti C, Appelbaum FR, Doney K, et al. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72:1924-1929. pmid: 11773890.
53. Schleuning M, Judith D, Jedlickova Z, Stübig T, Heshmat M, Baurmann H, Schwerdtfeger R. Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in allo-SCT for leukemia patients with high relapse risk: an observational cohort study. Bone Marrow Transplant. 2009;43:717-723. doi: 10.1038/bmt.2008.377.
57. Jedlickova Z, Burlakova I, Cook A, Baurmann H, Schwerdtfeger R, Schleuning M. mTOR inhibitors for treatment of sclerodermatous chronic graft-versus-host disease following allogeneic stem cell transplantation. Bone Marrow Transplant. 2009;43(suppl. 1):S123(abs.).
59. Kuppahally S, Al-Khaldi A, Weisshaar D, et al. Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients. Am.J.Transplant. 2006;6:986-992.
60. Klink A, Schilling K, Rapp K, Höffken K, Sayer HG. High overall response rate in calcineurin inhibitor-free treatment with the mTOR inhibitor everolimus in advanced extensive chronic GvHD after allogeneic stem cell transplantation. Blood. 2008;112:2210 (abs.).
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Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации
Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение
В-клеточных антител и иматиниба (ингибитора тирозинкиназы).
Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы.
Ключевые слова
хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат
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Keywords
chronic GVHD, calcineurin inhibitors, mTOR, extracorporal photopheresis, immunomodulatory drugs, steroids, methotrexate
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Keywords
chronic GVHD, calcineurin inhibitors, mTOR, extracorporal photopheresis, immunomodulatory drugs, steroids, methotrexate
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["PROPERTY_VALUE_ID"]=> string(5) "18592" ["VALUE"]=> array(2) { ["TEXT"]=> string(2566) "<p class="bodytext">Тяжёлые формы реакции «трансплантат против хозяина» (РТПХ) являются основной причиной заболеваемости и смертности у длительно живущих больных после трансплантации аллогенных гемопоэтических клеток. <br /><br />Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации<br> Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение<br> В-клеточных антител и иматиниба (ингибитора тирозинкиназы).<br /><br />Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы. </p> <h3>Ключевые слова</h3> <p> хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2484) "Тяжёлые формы реакции «трансплантат против хозяина» (РТПХ) являются основной причиной заболеваемости и смертности у длительно живущих больных после трансплантации аллогенных гемопоэтических клеток.
Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации
Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение
В-клеточных антител и иматиниба (ингибитора тирозинкиназы).
Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы.
Ключевые слова
хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(2484) "Тяжёлые формы реакции «трансплантат против хозяина» (РТПХ) являются основной причиной заболеваемости и смертности у длительно живущих больных после трансплантации аллогенных гемопоэтических клеток.
Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации
Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение
В-клеточных антител и иматиниба (ингибитора тирозинкиназы).
Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы.
Ключевые слова
хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат
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The majority of childhood leukemias have become curable via multi-agent chemotherapy. In subsets of children with high risk molecular subtypes of leukemia, poor response to induction chemotherapy or disease relapse, allogeneic hematopoietic stem cell transplantation (HSCT) today significantly contributes to relapse-free survival [1-3]. Both donor T cells and NK cells within the stem cell graft have been suggested to mediate potent anti-leukemic responses accounting for control of minimal residual disease and maintenance of remission. Unfortunately, data regarding the contribution of GVL activity to clinical disease control is limited by the lack of valid methods for assessing immunological rejection of leukemia cells by donor-derived immune effector cells in vivo. Indirect evidence is provided by correlations of relapse-free survival (RFS) with the extent of HLA compatibility between donor and recipient, or with the occurrence of acute or chronic graft-versus-host disease (GVHD). Furthermore, the effects of tapering immunosuppressive therapy or of administering donor lymphocyte infusions (DLIs) on either RFS or donor chimerism and/or minimal residual disease (MRD) are interpreted as evidence for the anti-leukemic activity of donor T cells.
One example in childhood leukemias is based on a case report demonstrating rapid return of donor chimerism and sustained remission in a patient with relapsed juvenile myelomonocytic leukemia (JMML) after HSCT in response to a single dose of DLIs [4]. JMML is a rare clonal myeloproliferative disorder of early childhood for which allogeneic HSCT is the only curative strategy, resulting in event-free survival of about 50% of the children [5]. In a larger series of 21 children who received DLIs for mixed chimerism or relapse after allogeneic HSCT, responses were found in six patients [6]. Five of the responders developed GVHD following DLI, thus arguing against the specific recognition of leukemia-associated antigens and demonstrating the limitations of this strategy by alloreactivity against non-hematopoietic targets.
While a large number of studies have demonstrated an important role of GVL effects in adult patients receiving allogeneic transplants for acute myelogenous leukemia (AML) [7], experience in childhood AML is limited. Among 19 of 81 pediatric AML patients with increasing mixed chimerism, 15 children who received early immunological intervention had an increased probability for event-free survival (pEFS 36%) compared to the 4 patients without intervention (pEFS 0%, P<0.05) [8]. In another series of 13 children with high-risk AML in first or second remission, immunotherapeutic interventions after allogeneic HSCT, aiming at inducing limited GVHD, combined with a uniform myeloablative preparative regimen, yielded encouraging early results [9]. Studies in a larger number of children are needed to assess the potential benefits of inducing alloreactivity in childhood AML.
The role of GVL effects in acute lymphoblastic leukemia (ALL), including childhood ALL, is controversial. Suggestive for a contribution of alloreactivity to sustained remission after allogeneic HSCT was the observation that among 36 children with high-risk or relapsed ALL, relapses occurred only in those receiving transplants from HLA-matched sibling donors (MSD, 8/13), while children after alternative donor HSCT remained disease-free (0/13) [2]. A similar observation was reported from an independent cohort of 71 children, with a 3-year cumulative incidence of relapse of 55.6±12.3% for MSD versus 22.0±8.1% for MUD recipients (P=0.03) [10]. By contrast, a recent study demonstrated comparable outcomes of MSD (n=41) versus alternative donor transplantations (n=42) in children with ALL receiving an identical TBI-based preparative regimen, with alemtuzumab administered to alternative donor HSC recipients [11]. In summary, no definite conclusions can be drawn regarding potentially superior GVL effects of unrelated grafts and their contribution to the maintenance of remissions. An anti-leukemic effect of chronic GVHD in childhood ALL was suggested by the results of a retrospective analysis of 450 children receiving allogeneic HSCT for hematologic malignancies, demonstrating a significantly reduced relapse probability in patients with chronic GVHD [12]. Importantly, stratifying the analysis by type of malignancy revealed a stronger correlation of chronic GVHD with relapse-free survival in ALL compared to other types of malignancies.
An important goal in advancing allogeneic HSCT for childhood leukemias is the development of therapeutic strategies that induce or augment GVL effects while avoiding clinical GVHD caused by alloreactivity with normal cells. In adults, administration of donor lymphocytes after HSCT has become an established treatment for high-risk myeloid malignancies [13]. The role of DLIs in childhood leukemias is less clear. In a cohort of 23 children with high-risk ALL, transfer of donor lymphocytes to children with decreasing donor chimerism prevented relapse in at least a proportion of patients [14]. However, unselected DLIs fail to rescue the majority of the children, and clinical GVHD remains a significant limitation to increasing cell doses. Efficient strategies for separating leukemia-reactive donor T cells from those responsible for GVHD are not yet available. While selective depletion of alloreactive T cells by an anti-CD25 immunotoxin prior to infusion of donor T cells following T-cell-depleted haploidentical SCT efficiently prevented GVHD [15], 7 of the 16 patients with malignant diseases in this cohort relapsed, arguing against preserved anti-leukemic responses after allodepletion.
Strategies for augmenting GVL effects in childhood leukemia
One means of generating large numbers of leukemia-specific T cells is genetic modification with antigen-specific chimeric receptors (CARs). CARs consist of an antibody-derived single chain Fv domain linked to a cytoplasmic signaling domain, generally derived from the T cell receptor (TCR) ζ chain [16]. Thereby, they redirect the T-cell effector function to a defined surface antigen and allow for the recognition of target cells in an HLA-independent manner. Increased awareness of the importance of co-stimulatory signaling in T cell activation has led to the design of “second-generation” CARs with co-stimulatory signaling components. These optimized CARs indeed promote superior T cell proliferation, persistence and tumor control in vivo [17, 18]. Recently, T cells expressing antigen-specific CARs have entered the first clinical trials [19-21]. While CAR gene-modified polyclonal donor T cells can mediate alloreactivity via their native receptors, genetic engineering of T cells with native specificity for a viral antigen may reduce the risk of GVHD while contributing to the reconstitution of virus-specific immune responses following HSCT [22, 23].
The specificity and efficacy of the approach depend on the choice of an appropriate target antigen expressed at high densities on the leukemia cells. An attractive target structure for B-cell malignancies, including B-cell precursor ALL of childhood, is the B-lineage antigen CD19. The specificity of CD19 for the leukemic clone is limited by co-expression on normal B precursor cells and B cells, which will result in a transient defect of B-cell maturation as an undesired side effect of effective CD19-directed immunotherapy. CD19-specific CARs have been shown by various investigators to mediate potent anti-leukemic T-cell responses both in vitro and in vivo [24-26], and their therapeutic efficacy is being evaluated in ongoing clinical studies.
Besides modifying the antigen specificity of T cells, CARs can be used to redirect natural killer cells (NK cells) to leukemia cells. Alloreactive NK cells have been shown to persist in pediatric patients following KIR ligand-mismatched haploidentical HSCT, and are considered as being important players in anti-leukemic cellular immune responses after transplantation [27]. Protocols for the large-scale in vitro activation and expansion of human NK cells for adoptive transfer have been developed [28]. Expression of CD19-specific CARs in human NK cells [29, 30] triggers powerful and antigen-specific stimulatory signals, inducing cytolysis of otherwise NK-cell resistant leukemia cell lines and autologous leukemia cells [29, 31].
Key issues regarding long-term control of leukemia by cellular immunotherapies are in vivo persistence and functional reactivation of the transferred effector cell populations within the immunosuppressive leukemic microenvironment. Dual-specific T cells with native specificity for a strong viral antigen, e.g. EBV, reengineered to interact with leukemia-associated antigens via CARs, may have superior persistence in vivo and receive potent reactivation stimuli via CARs. Indeed, CAR-transduced EBV-CTLs have been shown to persist for several weeks in the peripheral blood of neuroblastoma patients [21]. Alternative designs of dual-specific T-cells, e.g. carrying a specificity against varicella-zoster virus, might even allow for vaccination strategies to boost and prolong the presence of specific effector cells in vivo [22].
Persistence of gene-modified T cells was further shown when the transfer of gene-modified T cells was preceded by a lymphodepletive regimen [32], which was attributed to a favorable homeostatic cytokine environment and by elimination of regulatory T cells. Selective depletion of regulatory T cells by the CD25-specific antibody denileukin difitox in melanoma patients enhanced the efficacy of a tumor vaccine; however, responsive patients also had severe autoimmune manifestations [33]. Therefore, selective elimination of regulatory T cells in patients after allogeneic HSCT, will likely induce or augment clinical GVHD – again illustrating the dilemma of obtaining a favorable balance between GVL and GVHD.
Conclusions
Specific cellular immunotherapeutic strategies may prove effective in preventing relapse in children who cannot be cured by allogeneic HSCT alone. Using molecular minimal residual disease monitoring, patients with the highest risk of relapse can now be identified prior to HSCT[1], thus providing a platform for evaluation of the efficacy of immune-based strategies. Besides maximal reduction of leukemia bulk prior to cellular therapy, selective depletion of regulatory T cells, as well as generation of an optimized cytokine milieu and subsequent boosting of anti-leukemic immune responses by vaccination may contribute to generating therapeutic GVL effects (Figure 1).
Figure 1. Implementation of immunotherapeutic strategies into the treatment of high-risk childhood leukemia
References
1. Bader P, Eckert C, Kreyenberg H, et al. Predictive Value of Mrd Prior to Allogeneic Sct in Relapsed Childhood Acute Lymphoblastic Leukemia - Analysis of the All-Rez Bfm Group. Biology of Blood and Marrow Transplantation. 2008;14:23.
6. Yoshimi A, Bader P, Matthes-Martin S, et al. Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia. Leukemia. 2005;19:971-977.
11. Kennedy-Nasser AA, Bollard CM, Myers GD, et al. Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. Biol Blood Marrow Transplant. 2008;14:1245-1252.
17. Finney HM, Lawson AD, Bebbington CR, Weir AN. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol. 1998;161:2791-2797.
18. Maher J, Brentjens RJ, Gunset G, Riviere I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol. 2002;20:70-75.
20. Till BG, Jensen MC, Wang J, Chen EY, Wood BL, Greisman HA, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood. 2008;112:2261-2271.
21. Pule MA, Savoldo B, Myers GD, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008;14:1264-1270.
24. Brentjens RJ, Latouche JB, Santos E, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nature Medicine. 2003;9:279-286.
25. Cooper LJN, Topp MS, Serrano LM, et al. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood. 2003;101:1637-1644.
26. Rossig C, Pscherer S, Landmeier S, et al. Adoptive cellular immunotherapy with CD19-specific T cells. Klin Padiatr. 2005;217:351-356.
27. Pende D, Marcenaro S, Falco M, et al. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood. 2009;113:3119-3129.
28. Fujisaki H, Kakuda H, Shimasaki N, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009;69:4010-4017.
31. Altvater B, Landmeier S, Pscherer S, Temme J, Schweer K, Kailayangiri S, et al. 2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. Clinical Cancer Research in press. 2009.
" ["~DETAIL_TEXT"]=> string(23789) "Evidence for GVL effects in childhood leukemias
The majority of childhood leukemias have become curable via multi-agent chemotherapy. In subsets of children with high risk molecular subtypes of leukemia, poor response to induction chemotherapy or disease relapse, allogeneic hematopoietic stem cell transplantation (HSCT) today significantly contributes to relapse-free survival [1-3]. Both donor T cells and NK cells within the stem cell graft have been suggested to mediate potent anti-leukemic responses accounting for control of minimal residual disease and maintenance of remission. Unfortunately, data regarding the contribution of GVL activity to clinical disease control is limited by the lack of valid methods for assessing immunological rejection of leukemia cells by donor-derived immune effector cells in vivo. Indirect evidence is provided by correlations of relapse-free survival (RFS) with the extent of HLA compatibility between donor and recipient, or with the occurrence of acute or chronic graft-versus-host disease (GVHD). Furthermore, the effects of tapering immunosuppressive therapy or of administering donor lymphocyte infusions (DLIs) on either RFS or donor chimerism and/or minimal residual disease (MRD) are interpreted as evidence for the anti-leukemic activity of donor T cells.
One example in childhood leukemias is based on a case report demonstrating rapid return of donor chimerism and sustained remission in a patient with relapsed juvenile myelomonocytic leukemia (JMML) after HSCT in response to a single dose of DLIs [4]. JMML is a rare clonal myeloproliferative disorder of early childhood for which allogeneic HSCT is the only curative strategy, resulting in event-free survival of about 50% of the children [5]. In a larger series of 21 children who received DLIs for mixed chimerism or relapse after allogeneic HSCT, responses were found in six patients [6]. Five of the responders developed GVHD following DLI, thus arguing against the specific recognition of leukemia-associated antigens and demonstrating the limitations of this strategy by alloreactivity against non-hematopoietic targets.
While a large number of studies have demonstrated an important role of GVL effects in adult patients receiving allogeneic transplants for acute myelogenous leukemia (AML) [7], experience in childhood AML is limited. Among 19 of 81 pediatric AML patients with increasing mixed chimerism, 15 children who received early immunological intervention had an increased probability for event-free survival (pEFS 36%) compared to the 4 patients without intervention (pEFS 0%, P<0.05) [8]. In another series of 13 children with high-risk AML in first or second remission, immunotherapeutic interventions after allogeneic HSCT, aiming at inducing limited GVHD, combined with a uniform myeloablative preparative regimen, yielded encouraging early results [9]. Studies in a larger number of children are needed to assess the potential benefits of inducing alloreactivity in childhood AML.
The role of GVL effects in acute lymphoblastic leukemia (ALL), including childhood ALL, is controversial. Suggestive for a contribution of alloreactivity to sustained remission after allogeneic HSCT was the observation that among 36 children with high-risk or relapsed ALL, relapses occurred only in those receiving transplants from HLA-matched sibling donors (MSD, 8/13), while children after alternative donor HSCT remained disease-free (0/13) [2]. A similar observation was reported from an independent cohort of 71 children, with a 3-year cumulative incidence of relapse of 55.6±12.3% for MSD versus 22.0±8.1% for MUD recipients (P=0.03) [10]. By contrast, a recent study demonstrated comparable outcomes of MSD (n=41) versus alternative donor transplantations (n=42) in children with ALL receiving an identical TBI-based preparative regimen, with alemtuzumab administered to alternative donor HSC recipients [11]. In summary, no definite conclusions can be drawn regarding potentially superior GVL effects of unrelated grafts and their contribution to the maintenance of remissions. An anti-leukemic effect of chronic GVHD in childhood ALL was suggested by the results of a retrospective analysis of 450 children receiving allogeneic HSCT for hematologic malignancies, demonstrating a significantly reduced relapse probability in patients with chronic GVHD [12]. Importantly, stratifying the analysis by type of malignancy revealed a stronger correlation of chronic GVHD with relapse-free survival in ALL compared to other types of malignancies.
An important goal in advancing allogeneic HSCT for childhood leukemias is the development of therapeutic strategies that induce or augment GVL effects while avoiding clinical GVHD caused by alloreactivity with normal cells. In adults, administration of donor lymphocytes after HSCT has become an established treatment for high-risk myeloid malignancies [13]. The role of DLIs in childhood leukemias is less clear. In a cohort of 23 children with high-risk ALL, transfer of donor lymphocytes to children with decreasing donor chimerism prevented relapse in at least a proportion of patients [14]. However, unselected DLIs fail to rescue the majority of the children, and clinical GVHD remains a significant limitation to increasing cell doses. Efficient strategies for separating leukemia-reactive donor T cells from those responsible for GVHD are not yet available. While selective depletion of alloreactive T cells by an anti-CD25 immunotoxin prior to infusion of donor T cells following T-cell-depleted haploidentical SCT efficiently prevented GVHD [15], 7 of the 16 patients with malignant diseases in this cohort relapsed, arguing against preserved anti-leukemic responses after allodepletion.
Strategies for augmenting GVL effects in childhood leukemia
One means of generating large numbers of leukemia-specific T cells is genetic modification with antigen-specific chimeric receptors (CARs). CARs consist of an antibody-derived single chain Fv domain linked to a cytoplasmic signaling domain, generally derived from the T cell receptor (TCR) ζ chain [16]. Thereby, they redirect the T-cell effector function to a defined surface antigen and allow for the recognition of target cells in an HLA-independent manner. Increased awareness of the importance of co-stimulatory signaling in T cell activation has led to the design of “second-generation” CARs with co-stimulatory signaling components. These optimized CARs indeed promote superior T cell proliferation, persistence and tumor control in vivo [17, 18]. Recently, T cells expressing antigen-specific CARs have entered the first clinical trials [19-21]. While CAR gene-modified polyclonal donor T cells can mediate alloreactivity via their native receptors, genetic engineering of T cells with native specificity for a viral antigen may reduce the risk of GVHD while contributing to the reconstitution of virus-specific immune responses following HSCT [22, 23].
The specificity and efficacy of the approach depend on the choice of an appropriate target antigen expressed at high densities on the leukemia cells. An attractive target structure for B-cell malignancies, including B-cell precursor ALL of childhood, is the B-lineage antigen CD19. The specificity of CD19 for the leukemic clone is limited by co-expression on normal B precursor cells and B cells, which will result in a transient defect of B-cell maturation as an undesired side effect of effective CD19-directed immunotherapy. CD19-specific CARs have been shown by various investigators to mediate potent anti-leukemic T-cell responses both in vitro and in vivo [24-26], and their therapeutic efficacy is being evaluated in ongoing clinical studies.
Besides modifying the antigen specificity of T cells, CARs can be used to redirect natural killer cells (NK cells) to leukemia cells. Alloreactive NK cells have been shown to persist in pediatric patients following KIR ligand-mismatched haploidentical HSCT, and are considered as being important players in anti-leukemic cellular immune responses after transplantation [27]. Protocols for the large-scale in vitro activation and expansion of human NK cells for adoptive transfer have been developed [28]. Expression of CD19-specific CARs in human NK cells [29, 30] triggers powerful and antigen-specific stimulatory signals, inducing cytolysis of otherwise NK-cell resistant leukemia cell lines and autologous leukemia cells [29, 31].
Key issues regarding long-term control of leukemia by cellular immunotherapies are in vivo persistence and functional reactivation of the transferred effector cell populations within the immunosuppressive leukemic microenvironment. Dual-specific T cells with native specificity for a strong viral antigen, e.g. EBV, reengineered to interact with leukemia-associated antigens via CARs, may have superior persistence in vivo and receive potent reactivation stimuli via CARs. Indeed, CAR-transduced EBV-CTLs have been shown to persist for several weeks in the peripheral blood of neuroblastoma patients [21]. Alternative designs of dual-specific T-cells, e.g. carrying a specificity against varicella-zoster virus, might even allow for vaccination strategies to boost and prolong the presence of specific effector cells in vivo [22].
Persistence of gene-modified T cells was further shown when the transfer of gene-modified T cells was preceded by a lymphodepletive regimen [32], which was attributed to a favorable homeostatic cytokine environment and by elimination of regulatory T cells. Selective depletion of regulatory T cells by the CD25-specific antibody denileukin difitox in melanoma patients enhanced the efficacy of a tumor vaccine; however, responsive patients also had severe autoimmune manifestations [33]. Therefore, selective elimination of regulatory T cells in patients after allogeneic HSCT, will likely induce or augment clinical GVHD – again illustrating the dilemma of obtaining a favorable balance between GVL and GVHD.
Conclusions
Specific cellular immunotherapeutic strategies may prove effective in preventing relapse in children who cannot be cured by allogeneic HSCT alone. Using molecular minimal residual disease monitoring, patients with the highest risk of relapse can now be identified prior to HSCT[1], thus providing a platform for evaluation of the efficacy of immune-based strategies. Besides maximal reduction of leukemia bulk prior to cellular therapy, selective depletion of regulatory T cells, as well as generation of an optimized cytokine milieu and subsequent boosting of anti-leukemic immune responses by vaccination may contribute to generating therapeutic GVL effects (Figure 1).
Figure 1. Implementation of immunotherapeutic strategies into the treatment of high-risk childhood leukemia
References
1. Bader P, Eckert C, Kreyenberg H, et al. Predictive Value of Mrd Prior to Allogeneic Sct in Relapsed Childhood Acute Lymphoblastic Leukemia - Analysis of the All-Rez Bfm Group. Biology of Blood and Marrow Transplantation. 2008;14:23.
6. Yoshimi A, Bader P, Matthes-Martin S, et al. Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia. Leukemia. 2005;19:971-977.
11. Kennedy-Nasser AA, Bollard CM, Myers GD, et al. Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. Biol Blood Marrow Transplant. 2008;14:1245-1252.
17. Finney HM, Lawson AD, Bebbington CR, Weir AN. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol. 1998;161:2791-2797.
18. Maher J, Brentjens RJ, Gunset G, Riviere I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol. 2002;20:70-75.
20. Till BG, Jensen MC, Wang J, Chen EY, Wood BL, Greisman HA, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood. 2008;112:2261-2271.
21. Pule MA, Savoldo B, Myers GD, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008;14:1264-1270.
24. Brentjens RJ, Latouche JB, Santos E, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nature Medicine. 2003;9:279-286.
25. Cooper LJN, Topp MS, Serrano LM, et al. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood. 2003;101:1637-1644.
26. Rossig C, Pscherer S, Landmeier S, et al. Adoptive cellular immunotherapy with CD19-specific T cells. Klin Padiatr. 2005;217:351-356.
27. Pende D, Marcenaro S, Falco M, et al. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood. 2009;113:3119-3129.
28. Fujisaki H, Kakuda H, Shimasaki N, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009;69:4010-4017.
31. Altvater B, Landmeier S, Pscherer S, Temme J, Schweer K, Kailayangiri S, et al. 2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. Clinical Cancer Research in press. 2009.
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Роль и влияние реакции «трансплантат против лейкоза» (РТПЛ) на течение лейкоза у детей при аллогенной трансплантации не имеет детального объяснения. Эффективность в этих ситуациях основывается главным образом на связи клинических признаков наличия аллореактивности со стабильным полным донорским химеризмом и выживаемостью пациентов на фоне отсутствия рецидивов. Терапевтические подходы, специально направленные на усиление аллореактивности донорских клеток посредством ослабления иммуносупрессивных воздействий или введения лимфоцитов донора, ограничены возможностью развития реакции «трансплантат против хозяина» (РТПХ). Поэтому важной задачей на путях более широкого внедрения трансплантации аллогенных гемопоэтических стволовых клеток для лечения лейкозов у детей является разработка лечебной стратегии, которая позволит усилить РТПЛ и одновременно избежать РТПХ. Одна из таких стратегий подразумевает генетическую модификацию специфических рецепторов Т-клеток или НК-клеток, которая позволила бы распознавать антигены, ассоциированные с лейкозом. Современные разработки сфокусированы на дальнейшей оптимизации <i>in vivo</i> функциональной активности Т-клеток, в том числе их расселения («хоминга») в лейкозном микроокружении, длительного пребывания и способности к специфической реактивации в этой среде. </p> <h3>Ключевые слова</h3> <p> лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2954) "Трансплантация аллогенных гемопоэтических клеток (алло ТГСК) вносит существенный вклад в лечение детей, больных лейкозом с высокой вероятностью рецидива. Роль и влияние реакции «трансплантат против лейкоза» (РТПЛ) на течение лейкоза у детей при аллогенной трансплантации не имеет детального объяснения. Эффективность в этих ситуациях основывается главным образом на связи клинических признаков наличия аллореактивности со стабильным полным донорским химеризмом и выживаемостью пациентов на фоне отсутствия рецидивов. Терапевтические подходы, специально направленные на усиление аллореактивности донорских клеток посредством ослабления иммуносупрессивных воздействий или введения лимфоцитов донора, ограничены возможностью развития реакции «трансплантат против хозяина» (РТПХ). Поэтому важной задачей на путях более широкого внедрения трансплантации аллогенных гемопоэтических стволовых клеток для лечения лейкозов у детей является разработка лечебной стратегии, которая позволит усилить РТПЛ и одновременно избежать РТПХ. Одна из таких стратегий подразумевает генетическую модификацию специфических рецепторов Т-клеток или НК-клеток, которая позволила бы распознавать антигены, ассоциированные с лейкозом. Современные разработки сфокусированы на дальнейшей оптимизации in vivo функциональной активности Т-клеток, в том числе их расселения («хоминга») в лейкозном микроокружении, длительного пребывания и способности к специфической реактивации в этой среде.
Ключевые слова
лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток
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" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18573" ["VALUE"]=> array(2) { ["TEXT"]=> string(1448) "<p class="bodytext">Allogeneic hematopoietic stem cell transplantation (HSCT) today contributes significantly to the cure of children with high-risk leukemias. The contribution of cellular graft-versus-leukemia (GVL) reactions to the anti-leukemic effects of allogeneic transplantation in pediatric leukemias has not been clarified in detail. Evidence is mainly based on indirect associations of clinical signs of alloreactivity with maintenance of full donor chimerism and relapse-free survival. Therapeutic interventions aimed at deliberately enhancing alloreactive donor cells via early reduction of immunosuppression or administration of donor lymphocytes are limited by the occurrence of graft-versus-host-disease (GVHD). Therefore, an important goal in advancing the use of allogeneic HSCT as treatment for childhood leukemias is the development of therapeutic strategies that induce or augment GVL effects while avoiding GVHD. One potential strategy relies on genetic modification of the receptor specificity of T cells or NK cells to recognize leukemia-associated antigens. Current efforts further focus on an optimal in vivo functionality of therapeutic T cells, including homing to the leukemia microenvironment, persistence, and capacity for specific reactivation.<br /><br /> <h3>Keywords</h3> <p> leukemia, pediatric oncology, T cells, immunotherapy, adoptive T cell transfer </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1396) "Allogeneic hematopoietic stem cell transplantation (HSCT) today contributes significantly to the cure of children with high-risk leukemias. The contribution of cellular graft-versus-leukemia (GVL) reactions to the anti-leukemic effects of allogeneic transplantation in pediatric leukemias has not been clarified in detail. Evidence is mainly based on indirect associations of clinical signs of alloreactivity with maintenance of full donor chimerism and relapse-free survival. Therapeutic interventions aimed at deliberately enhancing alloreactive donor cells via early reduction of immunosuppression or administration of donor lymphocytes are limited by the occurrence of graft-versus-host-disease (GVHD). Therefore, an important goal in advancing the use of allogeneic HSCT as treatment for childhood leukemias is the development of therapeutic strategies that induce or augment GVL effects while avoiding GVHD. One potential strategy relies on genetic modification of the receptor specificity of T cells or NK cells to recognize leukemia-associated antigens. Current efforts further focus on an optimal in vivo functionality of therapeutic T cells, including homing to the leukemia microenvironment, persistence, and capacity for specific reactivation.
Keywords
leukemia, pediatric oncology, T cells, immunotherapy, adoptive T cell transfer
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leukemia, pediatric oncology, T cells, immunotherapy, adoptive T cell transfer
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Keywords
leukemia, pediatric oncology, T cells, immunotherapy, adoptive T cell transfer
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string(5) "18567" ["VALUE"]=> array(2) { ["TEXT"]=> string(3012) "<p class="bodytext">Трансплантация аллогенных гемопоэтических клеток (алло ТГСК) вносит существенный вклад в лечение детей, больных лейкозом с высокой вероятностью рецидива. Роль и влияние реакции «трансплантат против лейкоза» (РТПЛ) на течение лейкоза у детей при аллогенной трансплантации не имеет детального объяснения. Эффективность в этих ситуациях основывается главным образом на связи клинических признаков наличия аллореактивности со стабильным полным донорским химеризмом и выживаемостью пациентов на фоне отсутствия рецидивов. Терапевтические подходы, специально направленные на усиление аллореактивности донорских клеток посредством ослабления иммуносупрессивных воздействий или введения лимфоцитов донора, ограничены возможностью развития реакции «трансплантат против хозяина» (РТПХ). Поэтому важной задачей на путях более широкого внедрения трансплантации аллогенных гемопоэтических стволовых клеток для лечения лейкозов у детей является разработка лечебной стратегии, которая позволит усилить РТПЛ и одновременно избежать РТПХ. Одна из таких стратегий подразумевает генетическую модификацию специфических рецепторов Т-клеток или НК-клеток, которая позволила бы распознавать антигены, ассоциированные с лейкозом. Современные разработки сфокусированы на дальнейшей оптимизации <i>in vivo</i> функциональной активности Т-клеток, в том числе их расселения («хоминга») в лейкозном микроокружении, длительного пребывания и способности к специфической реактивации в этой среде. </p> <h3>Ключевые слова</h3> <p> лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2954) "Трансплантация аллогенных гемопоэтических клеток (алло ТГСК) вносит существенный вклад в лечение детей, больных лейкозом с высокой вероятностью рецидива. Роль и влияние реакции «трансплантат против лейкоза» (РТПЛ) на течение лейкоза у детей при аллогенной трансплантации не имеет детального объяснения. Эффективность в этих ситуациях основывается главным образом на связи клинических признаков наличия аллореактивности со стабильным полным донорским химеризмом и выживаемостью пациентов на фоне отсутствия рецидивов. Терапевтические подходы, специально направленные на усиление аллореактивности донорских клеток посредством ослабления иммуносупрессивных воздействий или введения лимфоцитов донора, ограничены возможностью развития реакции «трансплантат против хозяина» (РТПХ). Поэтому важной задачей на путях более широкого внедрения трансплантации аллогенных гемопоэтических стволовых клеток для лечения лейкозов у детей является разработка лечебной стратегии, которая позволит усилить РТПЛ и одновременно избежать РТПХ. Одна из таких стратегий подразумевает генетическую модификацию специфических рецепторов Т-клеток или НК-клеток, которая позволила бы распознавать антигены, ассоциированные с лейкозом. Современные разработки сфокусированы на дальнейшей оптимизации in vivo функциональной активности Т-клеток, в том числе их расселения («хоминга») в лейкозном микроокружении, длительного пребывания и способности к специфической реактивации в этой среде.
Ключевые слова
лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(2954) "Трансплантация аллогенных гемопоэтических клеток (алло ТГСК) вносит существенный вклад в лечение детей, больных лейкозом с высокой вероятностью рецидива. Роль и влияние реакции «трансплантат против лейкоза» (РТПЛ) на течение лейкоза у детей при аллогенной трансплантации не имеет детального объяснения. Эффективность в этих ситуациях основывается главным образом на связи клинических признаков наличия аллореактивности со стабильным полным донорским химеризмом и выживаемостью пациентов на фоне отсутствия рецидивов. Терапевтические подходы, специально направленные на усиление аллореактивности донорских клеток посредством ослабления иммуносупрессивных воздействий или введения лимфоцитов донора, ограничены возможностью развития реакции «трансплантат против хозяина» (РТПХ). Поэтому важной задачей на путях более широкого внедрения трансплантации аллогенных гемопоэтических стволовых клеток для лечения лейкозов у детей является разработка лечебной стратегии, которая позволит усилить РТПЛ и одновременно избежать РТПХ. Одна из таких стратегий подразумевает генетическую модификацию специфических рецепторов Т-клеток или НК-клеток, которая позволила бы распознавать антигены, ассоциированные с лейкозом. Современные разработки сфокусированы на дальнейшей оптимизации in vivo функциональной активности Т-клеток, в том числе их расселения («хоминга») в лейкозном микроокружении, длительного пребывания и способности к специфической реактивации в этой среде.
Ключевые слова
лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток
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Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ). </p> <p class="bodytext"> Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам <span lang="EN-US">CD</span><span lang="RU">8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.</span> </p> <p class="bodytext"> Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (<span lang="EN-US">CD</span><span lang="RU">25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением </span><span lang="EN-US">CD</span><span lang="RU">6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. </span>Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение <i><span lang="EN-US">in</span><span lang="EN-US"> </span></i><i><span lang="EN-US">vitro</span></i><span lang="EN-US"> </span><span lang="RU">и </span><span lang="EN-US">i<i>n</i></span><i><span lang="EN-US"> </span></i><i><span lang="EN-US">vivo</span><span lang="EN-US"> </span></i><span lang="RU">в целях профилактики развития лимфом и их контроля в клинических условиях.</span> </p> <p class="bodytext"> Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов. </p> <p class="bodytext"> <strong>Ключевые слова</strong><br> <span lang="RU"> хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, </span><span lang="EN-US">MHC</span><span lang="RU">-антигены, </span><span lang="EN-US">HLA</span><span lang="RU">-несовместимость, иммунная толерантность, антивирусный иммунитет</span> </p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(208) "Механизмы эффекта «трансплантат против лейкоза» после аллогенной трансплантации стволовых клеток (видеолекция)" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(208) "Механизмы эффекта «трансплантат против лейкоза» после аллогенной трансплантации стволовых клеток (видеолекция)" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(208) "Механизмы эффекта 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Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ). </p> <p class="bodytext"> Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам <span lang="EN-US">CD</span><span lang="RU">8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.</span> </p> <p class="bodytext"> Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (<span lang="EN-US">CD</span><span lang="RU">25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением </span><span lang="EN-US">CD</span><span lang="RU">6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. </span>Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение <i><span lang="EN-US">in</span><span lang="EN-US"> </span></i><i><span lang="EN-US">vitro</span></i><span lang="EN-US"> </span><span lang="RU">и </span><span lang="EN-US">i<i>n</i></span><i><span lang="EN-US"> </span></i><i><span lang="EN-US">vivo</span><span lang="EN-US"> </span></i><span lang="RU">в целях профилактики развития лимфом и их контроля в клинических условиях.</span> </p> <p class="bodytext"> Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов. </p> <p class="bodytext"> <strong>Ключевые слова</strong><br> <span lang="RU"> хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, </span><span lang="EN-US">MHC</span><span lang="RU">-антигены, </span><span lang="EN-US">HLA</span><span lang="RU">-несовместимость, иммунная толерантность, антивирусный иммунитет</span> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(7558) "Видеолекция
Лекция начинается историческими сведениями о трансплантации гемопоэтических стволовых клеток (ТГСК), а также о первом клиническом опыте алло-ТГСК с применением аллотрансплантата, лишенного Т-лимфоцитов. Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ).
Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам CD8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.
Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (CD25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по HLA-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением CD6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по HLA-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение in vitro и in vivo в целях профилактики развития лимфом и их контроля в клинических условиях.
Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов.
Ключевые слова
хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, MHC-антигены, HLA-несовместимость, иммунная толерантность, антивирусный иммунитет
Hans-Jochem Kolb
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Correspondence
Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81337 Munich, Germany
E-mail: Hans.Kolb@med.uni-muenchen.de
Videolection
The lecture begins by describing the historical features of hematopoietic stem cell transplantation (HSCT), followed by the first clinical experiences with T cell-depleted allografts. A concept of adoptive immune therapy is proposed for chimeric organisms after T-cell depleted grafting, aiming for an increased graft-versus-leukemia (GvL) effect.
The efficiency of donor lymphocyte transfusions (DLT) was extensively tested, being more expressed in chronic myeloid leukemia (CML). The intensity of graft-versus-host disease (GvHD), generally correlates with GvL, and is thus associated with an anti-leukemic response. Hence, DLT is a useful means of achieving long-term molecular remission in CML, as confirmed by EMBT studies.
The clinical efficiency of post-transplant adoptive immunotherapy was shown in EBMT trials. This effect is more pronounced in CML, since malignant myeloid precursors supposedly produce antigen-presenting dendritic cells (DCs). Within the general mechanism of GvHD, a 'cytokine storm' may promote this type of immune response. DCs present MHC antigens to the CD8+ effector cells, thus providing them with a 'license to kill'. A clinical protocol was introduced on this basis, using a combined therapeutic schedule including GM-CSF and carefully timed DLT procedures.
A theory of evolving immune tolerance is also discussed, encompassing specific interactions between host DCs and donor CD25+ regulatory T cells. A concept of central (thymus-dependent) tolerance is developed, primarily for children undergoing therapy. Haploidentical transplants are therefore considered with respect to increased NK cell production, especially in acute lymphoblastic leukemia (ALL). A possible role of HLA mismatches and the association between chronic GvHD (cGvHD) and long-term GvL effects is discussed, such as the favorable role of cGvHD in CML, unlike ALL. Fractionation of mobilized peripheral blood cells with CD6+ cell depletion proved to be a useful immune modulation tool.
The significance of HLA mismatches is discussed in connection with modulation of NK activity; this is presumably dependent upon specific interactions between homozygous and heterozygous immune cells, either of donor or recipient origin.
Antiviral immunity is also discussed: in particular, generation of anti-EBV-specific cells and their in vitro and in vivo expansion, aiming for potential lymphoma prevention and control in clinical settings.
Meanwhile, GvL is postulated to proceed either via naïve or memory T cell populations, as illustrated by cases of double cord blood transplantations. The possible mechanisms of graft-graft interactions are discussed.
Hence, adoptive immune therapy in chimeric patients should be regarded as an effective accessory tool for eradication of leukemic cells – at least in some types of leukemia.
Keywords
chronic myeloid leukemia, adoptive immune therapy, dendritic cells, T cells, HLA mismatch, immune tolerance, antiviral immunity
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The lecture begins by describing the historical features of hematopoietic stem cell transplantation (HSCT), followed by the first clinical experiences with T cell-depleted allografts. A concept of adoptive immune therapy is proposed for chimeric organisms after T-cell depleted grafting, aiming for an increased graft-versus-leukemia (GvL) effect.
The efficiency of donor lymphocyte transfusions (DLT) was extensively tested, being more expressed in chronic myeloid leukemia (CML). The intensity of graft-versus-host disease (GvHD), generally correlates with GvL, and is thus associated with an anti-leukemic response. Hence, DLT is a useful means of achieving long-term molecular remission in CML, as confirmed by EMBT studies.
The clinical efficiency of post-transplant adoptive immunotherapy was shown in EBMT trials. This effect is more pronounced in CML, since malignant myeloid precursors supposedly produce antigen-presenting dendritic cells (DCs). Within the general mechanism of GvHD, a 'cytokine storm' may promote this type of immune response. DCs present MHC antigens to the CD8+ effector cells, thus providing them with a 'license to kill'. A clinical protocol was introduced on this basis, using a combined therapeutic schedule including GM-CSF and carefully timed DLT procedures.
A theory of evolving immune tolerance is also discussed, encompassing specific interactions between host DCs and donor CD25+ regulatory T cells. A concept of central (thymus-dependent) tolerance is developed, primarily for children undergoing therapy. Haploidentical transplants are therefore considered with respect to increased NK cell production, especially in acute lymphoblastic leukemia (ALL). A possible role of HLA mismatches and the association between chronic GvHD (cGvHD) and long-term GvL effects is discussed, such as the favorable role of cGvHD in CML, unlike ALL. Fractionation of mobilized peripheral blood cells with CD6+ cell depletion proved to be a useful immune modulation tool.
The significance of HLA mismatches is discussed in connection with modulation of NK activity; this is presumably dependent upon specific interactions between homozygous and heterozygous immune cells, either of donor or recipient origin.
Antiviral immunity is also discussed: in particular, generation of anti-EBV-specific cells and their in vitro and in vivo expansion, aiming for potential lymphoma prevention and control in clinical settings.
Meanwhile, GvL is postulated to proceed either via naïve or memory T cell populations, as illustrated by cases of double cord blood transplantations. The possible mechanisms of graft-graft interactions are discussed.
Hence, adoptive immune therapy in chimeric patients should be regarded as an effective accessory tool for eradication of leukemic cells – at least in some types of leukemia.
Keywords
chronic myeloid leukemia, adoptive immune therapy, dendritic cells, T cells, HLA mismatch, immune tolerance, antiviral immunity
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The lecture begins by describing the historical features of hematopoietic stem cell transplantation (HSCT), followed by the first clinical experiences with T cell-depleted allografts. A concept of adoptive immune therapy is proposed for chimeric organisms after T-cell depleted grafting, aiming for an increased graft-versus-leukemia (GvL) effect.
The efficiency of donor lymphocyte transfusions (DLT) was extensively tested, being more expressed in chronic myeloid leukemia (CML). The intensity of graft-versus-host disease (GvHD), generally correlates with GvL, and is thus associated with an anti-leukemic response. Hence, DLT is a useful means of achieving long-term molecular remission in CML, as confirmed by EMBT studies.
The clinical efficiency of post-transplant adoptive immunotherapy was shown in EBMT trials. This effect is more pronounced in CML, since malignant myeloid precursors supposedly produce antigen-presenting dendritic cells (DCs). Within the general mechanism of GvHD, a 'cytokine storm' may promote this type of immune response. DCs present MHC antigens to the CD8+ effector cells, thus providing them with a 'license to kill'. A clinical protocol was introduced on this basis, using a combined therapeutic schedule including GM-CSF and carefully timed DLT procedures.
A theory of evolving immune tolerance is also discussed, encompassing specific interactions between host DCs and donor CD25+ regulatory T cells. A concept of central (thymus-dependent) tolerance is developed, primarily for children undergoing therapy. Haploidentical transplants are therefore considered with respect to increased NK cell production, especially in acute lymphoblastic leukemia (ALL). A possible role of HLA mismatches and the association between chronic GvHD (cGvHD) and long-term GvL effects is discussed, such as the favorable role of cGvHD in CML, unlike ALL. Fractionation of mobilized peripheral blood cells with CD6+ cell depletion proved to be a useful immune modulation tool.
The significance of HLA mismatches is discussed in connection with modulation of NK activity; this is presumably dependent upon specific interactions between homozygous and heterozygous immune cells, either of donor or recipient origin.
Antiviral immunity is also discussed: in particular, generation of anti-EBV-specific cells and their in vitro and in vivo expansion, aiming for potential lymphoma prevention and control in clinical settings.
Meanwhile, GvL is postulated to proceed either via naïve or memory T cell populations, as illustrated by cases of double cord blood transplantations. The possible mechanisms of graft-graft interactions are discussed.
Hence, adoptive immune therapy in chimeric patients should be regarded as an effective accessory tool for eradication of leukemic cells – at least in some types of leukemia.
Keywords
chronic myeloid leukemia, adoptive immune therapy, dendritic cells, T cells, HLA mismatch, immune tolerance, antiviral immunity
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Correspondence
Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81337 Munich, Germany
E-mail: Hans.Kolb@med.uni-muenchen.de
Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Germany
Correspondence
Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81337 Munich, Germany
E-mail: Hans.Kolb@med.uni-muenchen.de
Ханс-Йохем Кольб
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Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ). </p> <p class="bodytext"> Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам <span lang="EN-US">CD</span><span lang="RU">8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.</span> </p> <p class="bodytext"> Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (<span lang="EN-US">CD</span><span lang="RU">25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением </span><span lang="EN-US">CD</span><span lang="RU">6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. </span>Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение <i><span lang="EN-US">in</span><span lang="EN-US"> </span></i><i><span lang="EN-US">vitro</span></i><span lang="EN-US"> </span><span lang="RU">и </span><span lang="EN-US">i<i>n</i></span><i><span lang="EN-US"> </span></i><i><span lang="EN-US">vivo</span><span lang="EN-US"> </span></i><span lang="RU">в целях профилактики развития лимфом и их контроля в клинических условиях.</span> </p> <p class="bodytext"> Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов. </p> <p class="bodytext"> <strong>Ключевые слова</strong><br> <span lang="RU"> хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, </span><span lang="EN-US">MHC</span><span lang="RU">-антигены, </span><span lang="EN-US">HLA</span><span lang="RU">-несовместимость, иммунная толерантность, антивирусный иммунитет</span> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(7558) "Видеолекция
Лекция начинается историческими сведениями о трансплантации гемопоэтических стволовых клеток (ТГСК), а также о первом клиническом опыте алло-ТГСК с применением аллотрансплантата, лишенного Т-лимфоцитов. Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ).
Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам CD8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.
Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (CD25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по HLA-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением CD6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по HLA-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение in vitro и in vivo в целях профилактики развития лимфом и их контроля в клинических условиях.
Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов.
Ключевые слова
хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, MHC-антигены, HLA-несовместимость, иммунная толерантность, антивирусный иммунитет
Видеолекция
Лекция начинается историческими сведениями о трансплантации гемопоэтических стволовых клеток (ТГСК), а также о первом клиническом опыте алло-ТГСК с применением аллотрансплантата, лишенного Т-лимфоцитов. Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ).
Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам CD8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.
Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (CD25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по HLA-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением CD6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по HLA-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение in vitro и in vivo в целях профилактики развития лимфом и их контроля в клинических условиях.
Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов.
Ключевые слова
хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, MHC-антигены, HLA-несовместимость, иммунная толерантность, антивирусный иммунитет
Introduction
Acute graft-versus-host disease (aGvHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (aHSCT). The success of aHSCT relies on how well transplant-related morbidity and mortality can be controlled while preserving the graft-versus-leukemia (GvL) effect essential to prevent relapse. It is important to understand the underlying mechanisms and effectors of aGvHD in order to prevent this complication.
According to Billingham's Harvey lecture in 1966 there are three requirements for aGvHD to develop. “First, the graft must contain a sufficient number of immunologically competent cells. Second, the host must possess important transplantation alloantigens that are lacking in the donor graft, so that the host appears foreign to the graft, and is, therefore, capable of stimulating it in an antigen dependent manner. Third, the host itself must be incapable of mounting an effective immunological reaction against the graft, at least for sufficient time for the latter to manifest its immunological capabilities; that is, it must have the security to tenure.” for review see [9].
The incidence of aGvHD ranges from 40% to 80% and depends on known risk factors like age, donor relationship, HLA-match, sex, graft source, and type of immunosuppressive prophylaxis. The mortality associated with acute GvHD can be directly correlated with the clinical grade at the time of manifestation and the initial response to steroid therapy [6, 28]. In addition, the time of occurrence and the grading at given time-points after transplantation seems to be relevant for the prognosis of an individual patient [19].
Primary therapy
The three organs most affected by aGvHD are the skin, gastrointestinal tract, and liver. Typically, either > grade 1 skin involvement or visceral manifestations are observed before therapy is instituted. The restrictive use of steroids is mainly due to the morbidity and complications associated with high dose steroid therapy in patients who have undergone serial chemotherapy and conditioning therapy. An alternative approach would be to use lower doses of steroids earlier in the course of the disease.
In a recent retrospective analysis, Mielcarek and coworkers compared the outcome of patients with acute GvHD grade I–IV receiving either 1 or 2 mg/kg prednisolone [22]. The cumulative dose of steroids applied in the latter group was significantly higher compared to patients starting at lower doses, and this was associated with a higher incidence of invasive fungal infections and a prolonged hospital stay. The authors conclude that patients with grade I–II acute GvHD may only require 1 mg/kg prednisolone and do not benefit from higher doses. Most investigators try to achieve higher trough-blood levels of the concomitantly applied calcineurin inhibitors (e.g., Cyclosporine or Tacrolimus), which in most cases of acute GvHD are still part of the patients’ medication.
Salvage therapy
Definition
In most clinical trials steroid-refractory acute GvHD is defined as no improvement of symptoms after 5–7 days or progressive disease within 72 hours after the start of therapy.
These patients should receive second line therapy, ideally within a clinical trial. As there are not many pharmaceutical companies which are willing to sponsor clinical studies and academic institutions are paralyzed by current legislation, the majority of patients can not be included in such trials. Therefore the current table provides a number of compounds tested in prospective phase I/II trials with the respective response rates observed. Only very few prospective controlled clinical protocols have been performed for this indication and have not been able to demonstrate an advantage in overall survival.
|
Agent |
N |
Response rate |
Citation |
|---|---|---|---|
|
Antithymocyte globulin |
47 |
54% |
(MacMillan et al., 2002) |
|
Mycophenolate mofetil |
17 |
65% |
(Basara et al., 1998) |
|
Pentostatin |
23 |
74% |
(Bolanos-Meade et al., 2005) |
|
Etanercept |
13 |
46% |
(Busca et al., 2007) |
|
Denileukin difitox |
30 |
71% |
(Ho et al., 2004) |
|
Basiliximab |
23 |
83% |
(Schmidt-Hieber et al., 2005) |
|
Daclizumab |
43 |
51% |
(Przepiorka et al., 2000) |
|
Infliximab |
32 |
59% |
(Patriarca et al., 2004) |
|
Visilizumab |
44 |
32% |
(Carpenter et al., 2005) |
|
Orthoclone |
43 |
69% |
(Knop et al., 2005) |
|
MabCampath |
16 |
50% |
(Gomez-Almaguer et al., 2008) |
|
Sirolimus |
21 |
55% |
(Benito et al., 2001) |
Prospective controlled trials
Only very few of the aforementioned agents have been tested in randomized controlled trials. In first line therapy, daclizumab, an antibody competitively blocking the IL-2 receptor, when combined with steroids was prospectively compared with steroids alone [18]. Despite the encouraging phase II trials in steroid refractory disease, the combined use of this anti-CD25 antibody and steroids was associated with an inferior survival compared to the control arm. Similarly, anti-CD147 therapy compared with antithymocyte globulin (ATG) has lead to a non-significant survival disadvantage [20]. An European trial investigating the use of a murine anti-CD3 antibody (Orthoclone) for which production will be discontinued in 2010 has suggested a non-significant advantage for the combination of high-dose steroids (HDS) combined with orthoclone compared to HDS alone [15]. The lack of support by pharmaceutical companies and the difficulties with trial design and end-points in steroid refractory GvHD have currently abrogated most efforts in this area of clinical research.
Current strategies inaugurated by multi-institutional trial networks include randomized phase II trials with several arms which are designed to identify differences in survival early with the aim of switching to a phase III part of the trial thereafter. One recent example is the study published by Alousi et al which suggests an advantage for the combination of MMF with steroids [1]. Further follow-up is needed to confirm these findings.
Non-pharmacological interventions
Extracorporeal photopheresis
Very exciting results have been recently published for the effectiveness of extracorporeal photopheresis (ECP) by Greinix and coworkers. They have clearly demonstrated that interesting response rates can be achieved by the early use of ECP with minimal toxicity and the possibility of reduce steroid therapy earlier [12]. Current efforts have to confirm this single-institution experience in a prospective multicentre trial.
Mesenchymal stromal cells (MSC)
MSC were described two decades ago by Friedenstein [10]. Since that time their potential for regenerative therapies has been the focus of many research groups. In the recent past, their immunosuppressive and anti-inflammatory activity has been addressed and confirmed in-vitro and in-vivo. Katarina Le Blanc and coworkers described the first successful therapeutic use of donor-derived MSC in steroid-refractory GvHD [16]. Since then, several investigators have confirmed the potential use of MSC in patients with advanced GvHD [17]. The different cellular preparations and application protocols so far do not allow firm conclusions on the efficacy of MSC therapy in various settings to be drawn. Prospective randomized trials are currently under-way and will shed more light on this cellular therapeutic approach. One advantage over most alternative pharmacological strategies is that MSC infusion is not associated with acute and mid-term side effects of an increased rate of infectious complications.
Regulator T cells (Tregs)
Since the pivotal studies of Edinger and coworkers demonstrating the efficacy of the prophylactic infusion of donor-derived CD4+/CD25++/Foxp3+ regulatory T cells in a murine models [8], several translational research activities have tried to prepare the first human trials using donor or patient-derived regulatory T cells. Most intriguing are the findings of the preclinical studies in which the anti-leukemic efficacy of adoptively transferred donor effector cells (GvL reactions) were not suppressed by the co-infusion of Tregs. The current challenge is to develop clinical-grade strategies to generate a sufficient amount of pure Tregs for repetitive infusions. In-vitro selection and expansion protocols have been described and need further refinement to avoid the application of activated CD25+ T cells. Recent case reports and preliminary clinical data suggest that beside their prophylactic use, the therapeutic efficacy of Tregs may be expected in certain clinical situations [23]. Current clinical protocols have additionally focussed on the use of donor Tregs to allow infusion of conventional T cells ameliorating immune reconstitution in the haploidentical setting without the induction of GvHD. Dose-finding and feasibility studies are needed in order to develop Tregs into an additionalas therapeutic tool in high-risk patients with acute GvHD.
Supportive care
Many of the intensified immunosuppressive regimens described above leave the patient at an increased risk for opportunistic infections. Beside the use of pre-emptive antiviral therapy to control CMV reactivation occurring during the course of refractory GvHD, invasive fungal infections are the major threat for patients with GvHD undergoing intensified and prolonged immunosuppressive therapy. The development of new antifungal agents have definitively helped to ameliorate the perspectives for patients with acute GvHD. Current recommendations favour the use of prophylactic antifungal medication in patients receiving > 1–2 mg of systemic steroids. A prospective randomized trial of posaconazole vs. fluconazole suggested that compounds effective against aspergillus species are especially warranted in this indication [27].
Perspectives
Since the outcome of patients with acute GvHD not responding to primary therapy with steroids still remains unsatisfactory, future strategies will have to focus on the following questions.
• How can we predict the individual risk for the occurrence of GVHD and the chance for responding to steroids by using genetic screening methods besides the standard high-resolution HLA typing methods (e.g., Cytokine gene polymorphisms)?
• What is the optimum pharmacological or cellular therapy approach for each patient?
• Which strategies can be applied with synergy?
• Can new molecularly-defined approaches using small molecules that specifically target signalling pathways involved in the pathophysiology be implemented with less off-target toxicities?
References
2. Basara N, Blau WI, Romer E, Rudolphi M, Bischoff M, Kirsten D, Sanchez H, Gunzelmann S, Fauser AA. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant. 1998;22:61-65. pmid: 9678797.
3. Benito AI, Furlong T, Martin PJ, Anasetti C, Appelbaum FR, Doney K, Nash RA, Papayannopoulou T, Storb R, Sullivan KM, Witherspoon R, Deeg HJ. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72:1924-1929. pmid: 11773890.
8. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat. Med. 2003;9:1144-1150. doi: 10.1038/nm915.
10. Friedenstein AJ. Osteogenic stem cells in the bone marrow. Bone and Mineral Research. 1990;7:243-272.
11. Gomez-Almaguer D, Ruiz-Arguelles GJ, del CT-A, Gonzalez-Llano O, Gutierrez-Aguirre H, Cantu-Rodriguez O, Jaime-Perez J, Carrasco-Yalan A, Giralt S. Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2008;14:10-15.
14. Knop S, Hebart H, Gratwohl A, Kliem C, Faul C, Holler E, Apperley J, Kolb HJ, Schaefer A, Niederwieser D, Einsele H. Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party. Leukemia. 2007;21:1830-1833. doi: 10.1038/sj.leu.2404731.
16. Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439-1441. pmid: 15121408.
17. Le BK, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579-1586.
23. Paczesny S, Choi SW, Ferrara JL. Acute graft-versus-host disease: new treatment strategies. Curr. Opin. Hematol. 2009;16:427-436. pmid: 19812490.
27. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais dA, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N. Engl. J. Med. 2007;356:335-347. pmid: 17251530.
" ["~DETAIL_TEXT"]=> string(27936) "Introduction
Acute graft-versus-host disease (aGvHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (aHSCT). The success of aHSCT relies on how well transplant-related morbidity and mortality can be controlled while preserving the graft-versus-leukemia (GvL) effect essential to prevent relapse. It is important to understand the underlying mechanisms and effectors of aGvHD in order to prevent this complication.
According to Billingham's Harvey lecture in 1966 there are three requirements for aGvHD to develop. “First, the graft must contain a sufficient number of immunologically competent cells. Second, the host must possess important transplantation alloantigens that are lacking in the donor graft, so that the host appears foreign to the graft, and is, therefore, capable of stimulating it in an antigen dependent manner. Third, the host itself must be incapable of mounting an effective immunological reaction against the graft, at least for sufficient time for the latter to manifest its immunological capabilities; that is, it must have the security to tenure.” for review see [9].
The incidence of aGvHD ranges from 40% to 80% and depends on known risk factors like age, donor relationship, HLA-match, sex, graft source, and type of immunosuppressive prophylaxis. The mortality associated with acute GvHD can be directly correlated with the clinical grade at the time of manifestation and the initial response to steroid therapy [6, 28]. In addition, the time of occurrence and the grading at given time-points after transplantation seems to be relevant for the prognosis of an individual patient [19].
Primary therapy
The three organs most affected by aGvHD are the skin, gastrointestinal tract, and liver. Typically, either > grade 1 skin involvement or visceral manifestations are observed before therapy is instituted. The restrictive use of steroids is mainly due to the morbidity and complications associated with high dose steroid therapy in patients who have undergone serial chemotherapy and conditioning therapy. An alternative approach would be to use lower doses of steroids earlier in the course of the disease.
In a recent retrospective analysis, Mielcarek and coworkers compared the outcome of patients with acute GvHD grade I–IV receiving either 1 or 2 mg/kg prednisolone [22]. The cumulative dose of steroids applied in the latter group was significantly higher compared to patients starting at lower doses, and this was associated with a higher incidence of invasive fungal infections and a prolonged hospital stay. The authors conclude that patients with grade I–II acute GvHD may only require 1 mg/kg prednisolone and do not benefit from higher doses. Most investigators try to achieve higher trough-blood levels of the concomitantly applied calcineurin inhibitors (e.g., Cyclosporine or Tacrolimus), which in most cases of acute GvHD are still part of the patients’ medication.
Salvage therapy
Definition
In most clinical trials steroid-refractory acute GvHD is defined as no improvement of symptoms after 5–7 days or progressive disease within 72 hours after the start of therapy.
These patients should receive second line therapy, ideally within a clinical trial. As there are not many pharmaceutical companies which are willing to sponsor clinical studies and academic institutions are paralyzed by current legislation, the majority of patients can not be included in such trials. Therefore the current table provides a number of compounds tested in prospective phase I/II trials with the respective response rates observed. Only very few prospective controlled clinical protocols have been performed for this indication and have not been able to demonstrate an advantage in overall survival.
|
Agent |
N |
Response rate |
Citation |
|---|---|---|---|
|
Antithymocyte globulin |
47 |
54% |
(MacMillan et al., 2002) |
|
Mycophenolate mofetil |
17 |
65% |
(Basara et al., 1998) |
|
Pentostatin |
23 |
74% |
(Bolanos-Meade et al., 2005) |
|
Etanercept |
13 |
46% |
(Busca et al., 2007) |
|
Denileukin difitox |
30 |
71% |
(Ho et al., 2004) |
|
Basiliximab |
23 |
83% |
(Schmidt-Hieber et al., 2005) |
|
Daclizumab |
43 |
51% |
(Przepiorka et al., 2000) |
|
Infliximab |
32 |
59% |
(Patriarca et al., 2004) |
|
Visilizumab |
44 |
32% |
(Carpenter et al., 2005) |
|
Orthoclone |
43 |
69% |
(Knop et al., 2005) |
|
MabCampath |
16 |
50% |
(Gomez-Almaguer et al., 2008) |
|
Sirolimus |
21 |
55% |
(Benito et al., 2001) |
Prospective controlled trials
Only very few of the aforementioned agents have been tested in randomized controlled trials. In first line therapy, daclizumab, an antibody competitively blocking the IL-2 receptor, when combined with steroids was prospectively compared with steroids alone [18]. Despite the encouraging phase II trials in steroid refractory disease, the combined use of this anti-CD25 antibody and steroids was associated with an inferior survival compared to the control arm. Similarly, anti-CD147 therapy compared with antithymocyte globulin (ATG) has lead to a non-significant survival disadvantage [20]. An European trial investigating the use of a murine anti-CD3 antibody (Orthoclone) for which production will be discontinued in 2010 has suggested a non-significant advantage for the combination of high-dose steroids (HDS) combined with orthoclone compared to HDS alone [15]. The lack of support by pharmaceutical companies and the difficulties with trial design and end-points in steroid refractory GvHD have currently abrogated most efforts in this area of clinical research.
Current strategies inaugurated by multi-institutional trial networks include randomized phase II trials with several arms which are designed to identify differences in survival early with the aim of switching to a phase III part of the trial thereafter. One recent example is the study published by Alousi et al which suggests an advantage for the combination of MMF with steroids [1]. Further follow-up is needed to confirm these findings.
Non-pharmacological interventions
Extracorporeal photopheresis
Very exciting results have been recently published for the effectiveness of extracorporeal photopheresis (ECP) by Greinix and coworkers. They have clearly demonstrated that interesting response rates can be achieved by the early use of ECP with minimal toxicity and the possibility of reduce steroid therapy earlier [12]. Current efforts have to confirm this single-institution experience in a prospective multicentre trial.
Mesenchymal stromal cells (MSC)
MSC were described two decades ago by Friedenstein [10]. Since that time their potential for regenerative therapies has been the focus of many research groups. In the recent past, their immunosuppressive and anti-inflammatory activity has been addressed and confirmed in-vitro and in-vivo. Katarina Le Blanc and coworkers described the first successful therapeutic use of donor-derived MSC in steroid-refractory GvHD [16]. Since then, several investigators have confirmed the potential use of MSC in patients with advanced GvHD [17]. The different cellular preparations and application protocols so far do not allow firm conclusions on the efficacy of MSC therapy in various settings to be drawn. Prospective randomized trials are currently under-way and will shed more light on this cellular therapeutic approach. One advantage over most alternative pharmacological strategies is that MSC infusion is not associated with acute and mid-term side effects of an increased rate of infectious complications.
Regulator T cells (Tregs)
Since the pivotal studies of Edinger and coworkers demonstrating the efficacy of the prophylactic infusion of donor-derived CD4+/CD25++/Foxp3+ regulatory T cells in a murine models [8], several translational research activities have tried to prepare the first human trials using donor or patient-derived regulatory T cells. Most intriguing are the findings of the preclinical studies in which the anti-leukemic efficacy of adoptively transferred donor effector cells (GvL reactions) were not suppressed by the co-infusion of Tregs. The current challenge is to develop clinical-grade strategies to generate a sufficient amount of pure Tregs for repetitive infusions. In-vitro selection and expansion protocols have been described and need further refinement to avoid the application of activated CD25+ T cells. Recent case reports and preliminary clinical data suggest that beside their prophylactic use, the therapeutic efficacy of Tregs may be expected in certain clinical situations [23]. Current clinical protocols have additionally focussed on the use of donor Tregs to allow infusion of conventional T cells ameliorating immune reconstitution in the haploidentical setting without the induction of GvHD. Dose-finding and feasibility studies are needed in order to develop Tregs into an additionalas therapeutic tool in high-risk patients with acute GvHD.
Supportive care
Many of the intensified immunosuppressive regimens described above leave the patient at an increased risk for opportunistic infections. Beside the use of pre-emptive antiviral therapy to control CMV reactivation occurring during the course of refractory GvHD, invasive fungal infections are the major threat for patients with GvHD undergoing intensified and prolonged immunosuppressive therapy. The development of new antifungal agents have definitively helped to ameliorate the perspectives for patients with acute GvHD. Current recommendations favour the use of prophylactic antifungal medication in patients receiving > 1–2 mg of systemic steroids. A prospective randomized trial of posaconazole vs. fluconazole suggested that compounds effective against aspergillus species are especially warranted in this indication [27].
Perspectives
Since the outcome of patients with acute GvHD not responding to primary therapy with steroids still remains unsatisfactory, future strategies will have to focus on the following questions.
• How can we predict the individual risk for the occurrence of GVHD and the chance for responding to steroids by using genetic screening methods besides the standard high-resolution HLA typing methods (e.g., Cytokine gene polymorphisms)?
• What is the optimum pharmacological or cellular therapy approach for each patient?
• Which strategies can be applied with synergy?
• Can new molecularly-defined approaches using small molecules that specifically target signalling pathways involved in the pathophysiology be implemented with less off-target toxicities?
References
2. Basara N, Blau WI, Romer E, Rudolphi M, Bischoff M, Kirsten D, Sanchez H, Gunzelmann S, Fauser AA. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant. 1998;22:61-65. pmid: 9678797.
3. Benito AI, Furlong T, Martin PJ, Anasetti C, Appelbaum FR, Doney K, Nash RA, Papayannopoulou T, Storb R, Sullivan KM, Witherspoon R, Deeg HJ. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72:1924-1929. pmid: 11773890.
8. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat. Med. 2003;9:1144-1150. doi: 10.1038/nm915.
10. Friedenstein AJ. Osteogenic stem cells in the bone marrow. Bone and Mineral Research. 1990;7:243-272.
11. Gomez-Almaguer D, Ruiz-Arguelles GJ, del CT-A, Gonzalez-Llano O, Gutierrez-Aguirre H, Cantu-Rodriguez O, Jaime-Perez J, Carrasco-Yalan A, Giralt S. Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2008;14:10-15.
14. Knop S, Hebart H, Gratwohl A, Kliem C, Faul C, Holler E, Apperley J, Kolb HJ, Schaefer A, Niederwieser D, Einsele H. Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party. Leukemia. 2007;21:1830-1833. doi: 10.1038/sj.leu.2404731.
16. Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439-1441. pmid: 15121408.
17. Le BK, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579-1586.
23. Paczesny S, Choi SW, Ferrara JL. Acute graft-versus-host disease: new treatment strategies. Curr. Opin. Hematol. 2009;16:427-436. pmid: 19812490.
27. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais dA, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N. Engl. J. Med. 2007;356:335-347. pmid: 17251530.
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" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "18695" ["VALUE"]=> array(2) { ["TEXT"]=> string(3017) "<p class="bodytext">Первичная терапия острой болезни «трансплантат против хозяина (оРТПХ) II-IV степени все еще основана на применении кортикостероидов (например – преднизолона) в дозах 1-2 мг/кг. Обычно исследователи сочетают этот подход с терапевтическими дозами ингибиторов кальцинейрина, которые используются в целях профилактики. Больные, не отвечающие на лечение стероидами в течение 5-7 дней, или пациенты с прогрессированием заболевания в течение 72 часов представляют собой группу высокого риска, требующую дальнейшей эскалации иммуносупрессии. Фармакологическое лечение второй линии определяется, в основном, тактикой, применяемой в данном центре, или индивидуальными решениями, поскольку отсутствует стратегия повышения выживаемости, основанная на контролируемом проспективном клиническом испытании. Выявлены препараты, показавшие эффективность по данным II фазы клинических испытаний: микофенолят мофетил, метотрексат, пентостатин, ингибиторы mTOR, антитела, направленные против ФНО-альфа или ИЛ-2, а также моноклональные или поликлональные антитела против Т-клеток. К немедикаментозным средствам лечения относятся: экстракорпоральный фотоферез и инфузия аллогенных мезенхимных стромальных клеток. При большинстве воздействий более раннее лечение (напр., в течение 2 недель) связано с лучшим исходом. Однако общая эффективность и токсичность при большинстве подходов не являются удовлетворительными. Дальнейшие разработки состоят в использованиии регуляторных Т-клеток и более нацеленные методы с применением малых молекул, действующих на специфические сигнальные пути в антиген-презентирующих и эффекторных клетках. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2995) "Первичная терапия острой болезни «трансплантат против хозяина (оРТПХ) II-IV степени все еще основана на применении кортикостероидов (например – преднизолона) в дозах 1-2 мг/кг. Обычно исследователи сочетают этот подход с терапевтическими дозами ингибиторов кальцинейрина, которые используются в целях профилактики. Больные, не отвечающие на лечение стероидами в течение 5-7 дней, или пациенты с прогрессированием заболевания в течение 72 часов представляют собой группу высокого риска, требующую дальнейшей эскалации иммуносупрессии. Фармакологическое лечение второй линии определяется, в основном, тактикой, применяемой в данном центре, или индивидуальными решениями, поскольку отсутствует стратегия повышения выживаемости, основанная на контролируемом проспективном клиническом испытании. Выявлены препараты, показавшие эффективность по данным II фазы клинических испытаний: микофенолят мофетил, метотрексат, пентостатин, ингибиторы mTOR, антитела, направленные против ФНО-альфа или ИЛ-2, а также моноклональные или поликлональные антитела против Т-клеток. К немедикаментозным средствам лечения относятся: экстракорпоральный фотоферез и инфузия аллогенных мезенхимных стромальных клеток. При большинстве воздействий более раннее лечение (напр., в течение 2 недель) связано с лучшим исходом. Однако общая эффективность и токсичность при большинстве подходов не являются удовлетворительными. Дальнейшие разработки состоят в использованиии регуляторных Т-клеток и более нацеленные методы с применением малых молекул, действующих на специфические сигнальные пути в антиген-презентирующих и эффекторных клетках.
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К немедикаментозным средствам лечения относятся: экстракорпоральный фотоферез и инфузия аллогенных мезенхимных стромальных клеток. При большинстве воздействий более раннее лечение (напр., в течение 2 недель) связано с лучшим исходом. Однако общая эффективность и токсичность при большинстве подходов не являются удовлетворительными. Дальнейшие разработки состоят в использованиии регуляторных Т-клеток и более нацеленные методы с применением малых молекул, действующих на специфические сигнальные пути в антиген-презентирующих и эффекторных клетках. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2995) "Первичная терапия острой болезни «трансплантат против хозяина (оРТПХ) II-IV степени все еще основана на применении кортикостероидов (например – преднизолона) в дозах 1-2 мг/кг. Обычно исследователи сочетают этот подход с терапевтическими дозами ингибиторов кальцинейрина, которые используются в целях профилактики. Больные, не отвечающие на лечение стероидами в течение 5-7 дней, или пациенты с прогрессированием заболевания в течение 72 часов представляют собой группу высокого риска, требующую дальнейшей эскалации иммуносупрессии. Фармакологическое лечение второй линии определяется, в основном, тактикой, применяемой в данном центре, или индивидуальными решениями, поскольку отсутствует стратегия повышения выживаемости, основанная на контролируемом проспективном клиническом испытании. Выявлены препараты, показавшие эффективность по данным II фазы клинических испытаний: микофенолят мофетил, метотрексат, пентостатин, ингибиторы mTOR, антитела, направленные против ФНО-альфа или ИЛ-2, а также моноклональные или поликлональные антитела против Т-клеток. К немедикаментозным средствам лечения относятся: экстракорпоральный фотоферез и инфузия аллогенных мезенхимных стромальных клеток. При большинстве воздействий более раннее лечение (напр., в течение 2 недель) связано с лучшим исходом. Однако общая эффективность и токсичность при большинстве подходов не являются удовлетворительными. Дальнейшие разработки состоят в использованиии регуляторных Т-клеток и более нацеленные методы с применением малых молекул, действующих на специфические сигнальные пути в антиген-презентирующих и эффекторных клетках.
" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(2995) "Первичная терапия острой болезни «трансплантат против хозяина (оРТПХ) II-IV степени все еще основана на применении кортикостероидов (например – преднизолона) в дозах 1-2 мг/кг. Обычно исследователи сочетают этот подход с терапевтическими дозами ингибиторов кальцинейрина, которые используются в целях профилактики. Больные, не отвечающие на лечение стероидами в течение 5-7 дней, или пациенты с прогрессированием заболевания в течение 72 часов представляют собой группу высокого риска, требующую дальнейшей эскалации иммуносупрессии. Фармакологическое лечение второй линии определяется, в основном, тактикой, применяемой в данном центре, или индивидуальными решениями, поскольку отсутствует стратегия повышения выживаемости, основанная на контролируемом проспективном клиническом испытании. Выявлены препараты, показавшие эффективность по данным II фазы клинических испытаний: микофенолят мофетил, метотрексат, пентостатин, ингибиторы mTOR, антитела, направленные против ФНО-альфа или ИЛ-2, а также моноклональные или поликлональные антитела против Т-клеток. К немедикаментозным средствам лечения относятся: экстракорпоральный фотоферез и инфузия аллогенных мезенхимных стромальных клеток. При большинстве воздействий более раннее лечение (напр., в течение 2 недель) связано с лучшим исходом. Однако общая эффективность и токсичность при большинстве подходов не являются удовлетворительными. Дальнейшие разработки состоят в использованиии регуляторных Т-клеток и более нацеленные методы с применением малых молекул, действующих на специфические сигнальные пути в антиген-презентирующих и эффекторных клетках.
" } } } }01.03.2011
Афанасьев Б. В. (Санкт-Петербург, Россия)
Вагемакер Г. (Роттердам, Нидерланды)
Цандер А. Р. (Гамбург, Германия)
Чухловин А. Б. (Санкт-Петербург, Россия)
Фезе Б. (Гамбург, Германия)
Новик А. А. (Москва, Россия)
Клаудиа Кольтценбург (Гамбург, Германия)
Алейникова О. В. (Минск, Беларусь)
Алянский А. Л. (Санкт-Петербург, Россия)
Анагносту А. (Бостон, США)
Андреефф М. (Хьюстон, США)
Бaйков В. (Санкт-Петербург, Россия)
Баранов В. С. (Санкт-Петербург, Россия)
Бархатов И. М. (Санкт-Петербург, Россия)
Баум К. (Ганновер, Германия)
Бахер У. (Гамбург, Германия)
Билько Н. М. (Киев, Украина)
Борсет М. (Трондхейм, Норвегия)
Быков В. Л. (Санкт-Петербург, Россия)
Бюхнер Т. (Мюнстер, Германия)
Вестенфельдер К. (Солт-Лейк-Сити, США)
Вилесов А. Д. (Санкт-Петербург, Россия)
Вислофф Ф. (Осло, Норвегия)
Дини Дж. (Генуя, Италия)
Дризе Н. (Москва, Россия)
Галибин О. В. (Санкт-Петербург, Россия)
Ганзер А. (Ганновер, Германия)
Гранов Д. А. (Санкт-Петербург, Россия)
Звартау Э. Э. (Санкт-Петербург, Россия)
Зверев О. Г. (Санкт-Петербург, Россия)
Зубаровская Л. С.(Санкт-Петербург, Россия)
Иванов Р. А. (Москва, Россия)
Климко Н. Н. (Санкт-Петербург, Россия)
Коза В. (Пльзень, Чехия)
Кольб Х. (Мюнхен, Германия)
Коноплева М. (Хьюстон, США)
Крегер Н. (Гамбург, Германия)
Маликов А. Я. (Санкт-Петербург, Россия)
Менткевич Г. Л. (Москва, Россия)
Михайлова Н. Б. (Санкт-Петербург, Россия)
Наглер А. (Тель Хашомер, Израиль)
Неворотин А. И. (Санкт-Петербург, Россия)
Немков А. С. (Санкт-Петербург, Россия)
Нет Р. (Гамбург, Германия)
Остертаг В. (Гамбург, Германия)
Палутке М. (Детройт, США)
Румянцев А. Г. (Москва, Россия)
Савченко В. Г. (Москва, Россия)
Смирнов А. В. (Санкт-Петербург, Россия)
Тец В. В. (Санкт-Петербург, Россия)
То Б. (Аделаида, Австралия)
Тотолян А. А. (Санкт-Петербург, Россия)
Усс А. Л. (Минск, Беларусь)
Феррара Дж. (Энн Арбор, США)
Фиббе В. (Лейден, Нидерланды)
Штамм К. (Берлин, Германия)
Эвераус Х. (Тарту, Эстония)
Эгеланд Т. (Осло, Норвегия)
Эльстнер Е. (Берлин, Германия)
Эмануэль В. Л. (Санкт-Петербург, Россия)
Промежуточный отчёт
Иосиф Л. Чертков, Ольга А. Гуревич, Геннадий А. Удалов, Ирина Н. Шипунова, Нина И. Дризе
Форум
Мартин Феннер
Обзорные статьи
Альберто М. Мармонт
Статьи
Aндрей A. Новик1, Алексей Н. Кузнецов1,2, Владимир Я. Мельниченко1, Денис А. Федоренко1, Tатьяна И. Ионова3, Кира А. Курбатова3
Евгений П. Евдошенко, Людмила Ст. Зубаровская, Леонид Г. Заславский, Александр А. Скоромец, Сергей М. Алексеев, Юлия А. Станкевич, Наталья А. Тотолян, Борис В. Афанасьев
Татьяна И. Ионова, Денис А. Федоренко, Никита Е. Мочкин, Кира А. Курбатова, Андрей А. Новик
Елена Р. Черных, Екатерина Я. Шевела, Людмила В. Сахно, Марина А. Тихонова, Ярослав Л. Петровский, Александр А. Останин
Другие темы
Михаэл Шлёнинг
Ханс-Йохем Кольб
Мальте фон Бонин, Мартин Вермке, Уве Платцбекер, Йорген Радке, Нона Шайеги, Сузанна Гретцингер, Конрад Хойхель, Кристина Хелиг, Марк Шмитц, Герхард Энингер, Йоханнес Шетелиг, Марти Борнхойзер
Промежуточный отчёт
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[TEXT] => <p>Данная работа суммирует достижения профессора Иосифа Львовича Черткова в изучении клеток-предшественниц кроветворного стромального микроокружения. В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.</p>
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Иосиф Л. Чертков, Ольга А. Гуревич, Геннадий А. Удалов, Ирина Н. Шипунова, Нина И. Дризе
Данная работа суммирует достижения профессора Иосифа Львовича Черткова в изучении клеток-предшественниц кроветворного стромального микроокружения. В своих работах Чертков использовал уникальный функциональный метод анализа стромальных клеток-предшественниц – метод образования очагов эктопического кроветворения под капсулой почки сингенных с донорами костного мозга реципиентов. Было продемонстрировано наличие в костном мозге мезенхимальных стволовых клеток, способных к переносу кроветворного микрооружения, т.е. дифференцировке во все стромальные клеточные линии, и к самоподдержанию, т.е. многократному переносу кроветворного микроокружения. Были изучены радиочувствительность и пролиферативный потенциал мезенхимальных стволовых клеток. Показана важность сохранения межклеточных контактов для построения стромального микроокружения in vitro и in vivo. Выявлена иерархичная структура отдела мезенхимальных стволовых клеток и охарактеризован отдел более дифференцированных, индуцибельных клеток-предшественниц стромального микроокружения. Показано взаимное влияние кроветворных и стромальных клеток. Охарактеризованы некоторые пути регуляции стромальных предшественников. Данная компиляция работ И. Л. Черткова демонстрирует его вклад в изучение регулирующего кроветворение стромального микроокружения костного мозга.
Форум
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Reference management software has been used by researchers for more than 20 years to find, store, and organize references, and to write scholarly papers. Recently developed collaborative web-based tools have resulted in a number of interesting new features, and in a number of new reference managers. These developments are changing which reference managers we use, and how we use them.
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<h3>Keywords</h3>
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reference management, Web 2.0, citation
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Мартин Феннер
Программное обеспечение по управлению библиографическими списками используется уже более 20 лет для поиска, хранения и систематизации библиографического материала, а также для написания научных статей. Не так давно появились коллективные сетевые ресурсы, которые открыли новые интересные возможности и способствовали созданию новых приложений по работе с библиографиями. Эти наработки специфичны для каждого отдельного приложения.
Обзорные статьи
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[TEXT] => <p class="bodytext">Для обоснования целесообразности трансплантации гемопоэтических стволовых клеток (ТГСК) при тяжёлых аутоиммунных болезнях (ТАБ) приводятся результаты двух различных серий исследований. Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования.
</p>
<h3>Ключевые слова</h3>
<p>аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация
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Ключевые слова
аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация
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<h3>Keywords</h3>
<p>autoimmune diseases, hematopoietic stem cell transplantation </p>
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Keywords
autoimmune diseases, hematopoietic stem cell transplantation
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Альберто М. Мармонт
Для обоснования целесообразности трансплантации гемопоэтических стволовых клеток (ТГСК) при тяжёлых аутоиммунных болезнях (ТАБ) приводятся результаты двух различных серий исследований. Экспериментальные доказательства основываются на положительных результатах лечения ТАБ (волчанки) у мышей посредством трансплантации аллогенных, а также, что звучит почти невероятно, аутологичных гемопоэтических стволовых клеток. Клинические доказательства основываются на сообщениях о аллотрансплантациях, сделанных по поводу других заболеваний, в результате чего были успешно вылечены и сопуствующие ТАБ. В настоящее время продолжаются мультицентрические клинические исследования, результаты которых позволят сравнить лечебный эффект трансплантации аллогенных стволовых клеток (ТАСК) с уже наиболее положительно зарекомендовавшими себя схемами лечения ТАБ без применения ТГСК, хотя, не исключено, что в будущем, в каких-то конкретных клинических случаях могут быть использованы оба подхода, и существующая лечебная тактика будет скорректирована при появлении новых лечебных препаратов. На ТАСК возлагаются большие надежды, но никогда нельзя забывать о её последствиях - высокой смертности и осложнениях, прежде всего, в результате РТПХ, даже если для профилактики используют режимы предварительного кондиционирования.
Ключевые слова
аутоиммунные болезни, трансплантация гемопоэтических стволовых клеток, аллогенная трансплантация, аутологичная трансплантация
Обзорные статьи
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[TEXT] => <p class="bodytext">Высокодозная иммуносупрессивная терапия и трансплантация аутологичных гемопоэтических стволовых клеток (HSCT) была введена в практику лечения больных рассеянным склерозом (РС) в 1995 г. Было показано, что HSCT является здесь наиболее эффективной иммуносупрессивной и противовоспалительной терапией. <br /><br />Во всех сообщениях, начиная с 2000 г., отмечается существенное (почти на 100%) снижение, или полное исчезновение признаков заболевания (воспаления), выявляемое с помощью метода ядерно-магнитного резонанса, и этот эффект сохраняется в течение длительного времени, в отличие от всех других методов лечения РС. Несмотря на весьма впечатляющие результаты применения HSCT для лечения РС, её преимущества были продемонстрированы только в сравнительных исследованиях. Поэтому представляется абсолютно необходимым завершить текущие рандомизированные исследования по сравнению HSCT с митоксантроном (ASTIMS) или с другими стандартными методами терапии. Пока не будут получены окончательные результаты этих исследований, HSCT не может быть принят как общепризнанный метод лечения больных с РС, которые могут быть лишены возможности получить действительно эффективную иммуносупрессивную и иммуномодулирующую терапию с длительным положительным воздействием на течение болезни.
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Атанасиос Фассас
Высокодозная иммуносупрессивная терапия и трансплантация аутологичных гемопоэтических стволовых клеток (HSCT) была введена в практику лечения больных рассеянным склерозом (РС) в 1995 г. Было показано, что HSCT является здесь наиболее эффективной иммуносупрессивной и противовоспалительной терапией.
Во всех сообщениях, начиная с 2000 г., отмечается существенное (почти на 100%) снижение, или полное исчезновение признаков заболевания (воспаления), выявляемое с помощью метода ядерно-магнитного резонанса, и этот эффект сохраняется в течение длительного времени, в отличие от всех других методов лечения РС. Несмотря на весьма впечатляющие результаты применения HSCT для лечения РС, её преимущества были продемонстрированы только в сравнительных исследованиях. Поэтому представляется абсолютно необходимым завершить текущие рандомизированные исследования по сравнению HSCT с митоксантроном (ASTIMS) или с другими стандартными методами терапии. Пока не будут получены окончательные результаты этих исследований, HSCT не может быть принят как общепризнанный метод лечения больных с РС, которые могут быть лишены возможности получить действительно эффективную иммуносупрессивную и иммуномодулирующую терапию с длительным положительным воздействием на течение болезни.
Обзорные статьи
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Алоис Грэтвол
Проведение аутологичных и аллогенных трансплантаций гемопоэтических стволовых клеток (ТГСК) имеет ряд общих целей, а также некоторые четкие различия по задачам их применения. Вся имеющаяся в настоящее время информация предполагает, что аутологичные ТГСК должны оставаться стандартным подходом в клинической трансплантации для лечения больных с тяжелыми аутоиммунными заболеваниями, в том числе – при рассеянном склерозе. Выбор в пользу аллогенных ТГСК должен рассматриваться у немногих больных с особыми характеристиками, при которых, возможно, выгоднее использовать аллогенную ТГСК, например, для молодых пациентов без сопутствующих заболеваний и гематологических аутоиммунных цитопений.
Статьи
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<span lang="RU">Aндрей A. Новик<sup>1</sup>, Алексей Н. Кузнецов<sup>1,2</sup>, Владимир Я. Мельниченко<sup>1</sup>, Денис А. Федоренко<sup>1</sup>, Tатьяна И. Ионова<sup>3</sup>, Кира А. Курбатова<sup>3</sup></span>
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Aндрей A. Новик1, Алексей Н. Кузнецов1,2, Владимир Я. Мельниченко1, Денис А. Федоренко1, Tатьяна И. Ионова3, Кира А. Курбатова3
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[TEXT] => <p class="bodytext"><sup>1</sup>Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; <sup>2</sup>Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; <sup>3</sup>Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия<br /><br /><b>Контакт</b><br> А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия<br>
E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.rgvxg48Dqemp2vy');">ncrtc04@<span style="display:none;">spam is bad</span>mail.ru</a>, <a href="javascript:linkTo_UnCryptMailto('qempxs.ruspgDcerhib2vy');">nqolc@<span style="display:none;">spam is bad</span>yandex.ru</a>
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Контакт
А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия
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[TEXT] => <p class="bodytext">Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.<br /><br /><h3>Ключевые слова</h3>
<p>рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения
</p>
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Ключевые слова
рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения
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[TEXT] => <p class="bodytext"><sup>1</sup>Pirogov National Medical Surgical Center, Moscow, Russia; <sup>2</sup>Multinational Center for Quality of Life Research, Saint Petersburg, Russia
</p><br>
<p class="bodytext"><b>Correspondence</b><br> Professor Tatyana I. Ionova, Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., 191014 St. Petersburg, Russia <br>
E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.xmsr5:Dqemp2vy');">tion16@<span style="display:none;">spam is bad</span>mail.ru</a>
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Correspondence
Professor Tatyana I. Ionova, Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., 191014 St. Petersburg, Russia
E-mail: tion16@mail.ru
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[TEXT] => <p class="bodytext">High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) is a promising approach to the treatment of multiple sclerosis (MS) patients. The data obtained points to the feasibility of early, conventional, and salvage HDIT +ASCT in MS patients. Further studies should be done to investigate clinical and patient-reported outcomes in MS patients receiving early, conventional, and salvage transplantation to better define treatment success. The concept of HDIT +ASCT in MS opens a new window of opportunity for treatment of this patient population.</p>
<h3>Keywords</h3><p>multiple sclerosis, autologous stem cell transplantation, long-term clinical outcomes, early ASCT, conventional ASCT, salvage ASCT
</p>
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Keywords
multiple sclerosis, autologous stem cell transplantation, long-term clinical outcomes, early ASCT, conventional ASCT, salvage ASCT
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Традиционные методы иммуномодулирующей и иммуносупрессивной терапии рассеянного склероза (РС) не позволяют достичь выраженного и длительного терапевтического эффекта [4-7, 10]. Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). В настоящее время в мире выполнено более 700 трансплантаций больным с различными формами РС. Безопасность и эффективность метода изучена в международных многоцентровых исследованиях. К нерешенным вопросам ВИСТ+ТСКК относятся следующие: показания, методы трансплантации, режимы кондиционирования, деплеция Т-лимфоцитов, фармакоэкономическое обоснование и др. [3, 9, 11].<br>
<br>
Разработана концепция ВИСТ+ТКСК при РС, включающая следующие положения: содержание метода, основные показания, методика проведения трансплантации, общий алгоритм, направления дальнейших исследований. Основные положения концепции подтверждены результатами проспективного многоцентрового исследования Российской кооперативной группы клеточной терапии изучения эффективности ВИСТ+ТКСК у больных различными формами РС. <br>
<br>
В рамках концепции выделено две принципиальные цели лечения больных РС. Первая из них патогенетическая – остановить прогрессирование заболевания и предотвратить появление новых очагов демиелинизации в ЦНС за счет воздействия на иммунопатологический процесс на различных уровнях. Вторая цель, основная или конечная, состоит в сохранении и, по возможности, в улучшении качества жизни больных. Данные положения основаны на теории принятия решений в клинической медицине, согласно которой в формализованном виде существует три возможных цели лечения больного: <br>
<br>
I – излечение с учетом качества жизни больного после выздоровления, <br>
II – увеличение продолжительности жизни больного с учетом ее качества<br>
III – улучшение качества жизни больного. <br>
<br>
При РС, хроническом неизлечимом заболевании, в большинстве случаев не снижающем продолжительность жизни больного, максимально возможное восстановление и сохранение параметров качества жизни является приоритетной целью лечения. Вследствие этого, наряду с традиционными лабораторными и инструментальными тестами, описывающими изменения в течении патологического процесса на фоне терапии, к ключевым критериям эффективности лечения РС следует отнести и показатели качества жизни больного, отражающие сложный комплекс физических, психологических и социальных детерминант, свойственных конкретному индивидууму. <br>
<br>
Учитывая вышесказанное, в рамках концепции выделены 3 вида трансплантации, отличающиеся по целям и времени проведения операции [12, 13]<br>
<br>
<b>Ранняя трансплантация</b><br>
1. Патогенетическая цель – предупредить развитие необратимых изменений в ЦНС в результате иммунопатологического процесса.<br>
2. Основная цель – сохранить качество жизни больного, предотвратить формирование инвалидизации. <br>
3. Время проведения – в дебюте заболевания.<br>
<br>
<b>Этапная трансплантация</b><br>
4. Патогенетическая цель – остановить прогрессирование заболевания на фоне самоподдерживающегося иммунопатологического процесса, имеющихся очагов необратимых изменений и частично утраченных функций, предупредить появление новых очагов поражения.<br>
5. Основная цель – улучшить качество жизни больного и сохранить его на максимально возможном уровне, предупредить углубление инвалидизации пациента.<br>
6. Время проведения – на различных этапах прогрессирования РС при выходе заболевания из-под контроля традиционных методов лечения.<br>
<br>
<b>Трансплантация спасения<br>
</b>7. Патогенетическая цель – остановить прогрессирование заболевания на фоне большого количества очагов необратимых изменений и существенно нарушенных функций, предупредить появление новых очагов поражения.<br>
8. Основная цель – сохранить качество жизни больного на максимально возможном уровне, предотвратить наступление критической инвалидизации.<br>
9. Время проведения – в далеко зашедшей стадии заболевания при высокой активности иммунопатологического процесса, быстром прогрессировании инвалидизации больного.
</p>
<p class="bodytext">
В данном докладе представлены результаты исследования безопасности и эффективности ВИСТ+ТКСК у 132 больных РС, которым ВИСТ+ТКСК проведена в Военно-медицинской академии (Санкт-Петербург) и Национальном медико-хирургическом центре им. Н.И. Пирогова (Москва), начиная с 1999 года. В исследование включено 58 мужчин и 74 женщины; средний возраст – 33 года. У 57 пациентов была диагностирована вторично-прогрессирующая форма заболевания, у 23 – первично-прогрессирующая, у 9 – прогрессирующе-рецидивирующая и у 43 – рецидивирующая ремитирующая. Выделены три группы пациентов в зависимости от вида трансплантации: ранняя трансплантация проводилась при EDSS от 1,5 до 3,0; этапная трансплантация - при EDSS от 3,5 до 6,5; трансплантация спасения - при EDSS от 7,0 до 8,5. 83 пациентам была проведена этапная ВИСТ+ТКСК; 43 – ранняя трансплантация; 7 – трансплантация спасения. Для кондиционирования использовали режимы BEAM или mini-BEAM. Эффект ВИСТ+ТКСК оценивали по изменению степени инвалидизации больного и активности заболевания.<br>
<br>
Отдельно была выделена группа больных, которым проводили консолидирующую терапию (митоксантрон) после ВИСТ+ТКСК. В эту группу вошли пациенты, имеющие факторы риска. В настоящее время данная группа включает 34 пациента; анализ результатов лечения в этой группе будет проведен в декабре 2009г.<br>
<br>
При проведении ВИСТ+ТКСК не было летальных исходов, связанных с трансплантацией, а также тяжелых непрогнозируемых осложнений. У всех больных зарегистрирован ответ на лечение: у половины больных было зарегистрировано клиническое улучшение; у остальных – стабилизация состояния. По данным МРТ у всех больных имелось либо улучшение, либо стабилизация процесса. В отдаленные сроки после ВИСТ+ТКСК (2 года и более) у подавляющего большинства больных (более 90%) наблюдали клиническое улучшение или стабилизацию заболевания. По данным магнитно-резонансной томографии отсутствие активности заболевания зарегистрировано у всех больных с клиническим улучшением или стабилизацией. Особого внимания заслуживает группа больных, которым проведена ранняя ВИСТ+ТКСК, и группа больных, у которых трансплантацию проводили с применением немиелоаблативных режимов кондиционирования. <br>
<br>
ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
</p>
<h3>Литература</h3>
<p class="bodytext">
1. <a href="http://bloodjournal.hematologylibrary.org/cgi/reprint/91/7/2609" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Burt RK, et al. Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis. Blood. 1998;91:2609–2616</u></a><u>.</u>
</p>
<p class="bodytext">
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
</p>
<p class="bodytext">
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
</p>
<p class="bodytext">
4. <a href="http://www.nature.com/bmt/journal/v20/n8/pdf/1700944a.pdf" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Fassas A, et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997;20:631-638</u></a><u>.</u>
</p>
<p class="bodytext">
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
</p>
<p class="bodytext">
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
</p>
<p class="bodytext">
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
</p>
<p class="bodytext">
8. <a href="http://bloodjournal.hematologylibrary.org/cgi/content/full/102/7/2364" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Nash RA, et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood. 2003;102:2364-2372. doi: 10.1182/blood-2002-12-3908</u></a><u>.</u>
</p>
<p class="bodytext">
9. <a href="http://bloodjournal.hematologylibrary.org/cgi/content/full/105/6/2601" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Saccardi R, et al. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood. 2005;105:2601-2607. doi: 10.1182/blood-2004-08-3205</u></a><u>.</u>
</p>
<p class="bodytext">
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
</p>
<p class="bodytext">
11. <a href="typo3/1-2-shevchenko-et-al-2008dec3.html" title="Opens external link in new window" class="external-link-new-window"><u>Shevchenko Y, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis. Cellular Therapy and Transplantation (CTT). 2008;1:2. doi: 10.3205/ctt-2008-en-000025.01</u></a>.
</p>
<p class="bodytext">
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
</p>
<p class="bodytext">
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
</p>
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Традиционные методы иммуномодулирующей и иммуносупрессивной терапии рассеянного склероза (РС) не позволяют достичь выраженного и длительного терапевтического эффекта [4-7, 10]. Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). В настоящее время в мире выполнено более 700 трансплантаций больным с различными формами РС. Безопасность и эффективность метода изучена в международных многоцентровых исследованиях. К нерешенным вопросам ВИСТ+ТСКК относятся следующие: показания, методы трансплантации, режимы кондиционирования, деплеция Т-лимфоцитов, фармакоэкономическое обоснование и др. [3, 9, 11].
Разработана концепция ВИСТ+ТКСК при РС, включающая следующие положения: содержание метода, основные показания, методика проведения трансплантации, общий алгоритм, направления дальнейших исследований. Основные положения концепции подтверждены результатами проспективного многоцентрового исследования Российской кооперативной группы клеточной терапии изучения эффективности ВИСТ+ТКСК у больных различными формами РС.
В рамках концепции выделено две принципиальные цели лечения больных РС. Первая из них патогенетическая – остановить прогрессирование заболевания и предотвратить появление новых очагов демиелинизации в ЦНС за счет воздействия на иммунопатологический процесс на различных уровнях. Вторая цель, основная или конечная, состоит в сохранении и, по возможности, в улучшении качества жизни больных. Данные положения основаны на теории принятия решений в клинической медицине, согласно которой в формализованном виде существует три возможных цели лечения больного:
I – излечение с учетом качества жизни больного после выздоровления,
II – увеличение продолжительности жизни больного с учетом ее качества
III – улучшение качества жизни больного.
При РС, хроническом неизлечимом заболевании, в большинстве случаев не снижающем продолжительность жизни больного, максимально возможное восстановление и сохранение параметров качества жизни является приоритетной целью лечения. Вследствие этого, наряду с традиционными лабораторными и инструментальными тестами, описывающими изменения в течении патологического процесса на фоне терапии, к ключевым критериям эффективности лечения РС следует отнести и показатели качества жизни больного, отражающие сложный комплекс физических, психологических и социальных детерминант, свойственных конкретному индивидууму.
Учитывая вышесказанное, в рамках концепции выделены 3 вида трансплантации, отличающиеся по целям и времени проведения операции [12, 13]
Ранняя трансплантация
1. Патогенетическая цель – предупредить развитие необратимых изменений в ЦНС в результате иммунопатологического процесса.
2. Основная цель – сохранить качество жизни больного, предотвратить формирование инвалидизации.
3. Время проведения – в дебюте заболевания.
Этапная трансплантация
4. Патогенетическая цель – остановить прогрессирование заболевания на фоне самоподдерживающегося иммунопатологического процесса, имеющихся очагов необратимых изменений и частично утраченных функций, предупредить появление новых очагов поражения.
5. Основная цель – улучшить качество жизни больного и сохранить его на максимально возможном уровне, предупредить углубление инвалидизации пациента.
6. Время проведения – на различных этапах прогрессирования РС при выходе заболевания из-под контроля традиционных методов лечения.
Трансплантация спасения
7. Патогенетическая цель – остановить прогрессирование заболевания на фоне большого количества очагов необратимых изменений и существенно нарушенных функций, предупредить появление новых очагов поражения.
8. Основная цель – сохранить качество жизни больного на максимально возможном уровне, предотвратить наступление критической инвалидизации.
9. Время проведения – в далеко зашедшей стадии заболевания при высокой активности иммунопатологического процесса, быстром прогрессировании инвалидизации больного.
В данном докладе представлены результаты исследования безопасности и эффективности ВИСТ+ТКСК у 132 больных РС, которым ВИСТ+ТКСК проведена в Военно-медицинской академии (Санкт-Петербург) и Национальном медико-хирургическом центре им. Н.И. Пирогова (Москва), начиная с 1999 года. В исследование включено 58 мужчин и 74 женщины; средний возраст – 33 года. У 57 пациентов была диагностирована вторично-прогрессирующая форма заболевания, у 23 – первично-прогрессирующая, у 9 – прогрессирующе-рецидивирующая и у 43 – рецидивирующая ремитирующая. Выделены три группы пациентов в зависимости от вида трансплантации: ранняя трансплантация проводилась при EDSS от 1,5 до 3,0; этапная трансплантация - при EDSS от 3,5 до 6,5; трансплантация спасения - при EDSS от 7,0 до 8,5. 83 пациентам была проведена этапная ВИСТ+ТКСК; 43 – ранняя трансплантация; 7 – трансплантация спасения. Для кондиционирования использовали режимы BEAM или mini-BEAM. Эффект ВИСТ+ТКСК оценивали по изменению степени инвалидизации больного и активности заболевания.
Отдельно была выделена группа больных, которым проводили консолидирующую терапию (митоксантрон) после ВИСТ+ТКСК. В эту группу вошли пациенты, имеющие факторы риска. В настоящее время данная группа включает 34 пациента; анализ результатов лечения в этой группе будет проведен в декабре 2009г.
При проведении ВИСТ+ТКСК не было летальных исходов, связанных с трансплантацией, а также тяжелых непрогнозируемых осложнений. У всех больных зарегистрирован ответ на лечение: у половины больных было зарегистрировано клиническое улучшение; у остальных – стабилизация состояния. По данным МРТ у всех больных имелось либо улучшение, либо стабилизация процесса. В отдаленные сроки после ВИСТ+ТКСК (2 года и более) у подавляющего большинства больных (более 90%) наблюдали клиническое улучшение или стабилизацию заболевания. По данным магнитно-резонансной томографии отсутствие активности заболевания зарегистрировано у всех больных с клиническим улучшением или стабилизацией. Особого внимания заслуживает группа больных, которым проведена ранняя ВИСТ+ТКСК, и группа больных, у которых трансплантацию проводили с применением немиелоаблативных режимов кондиционирования.
ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Литература
2. Burt RK, et al. Autologous haematopoietic stem cell transplantation in multiple sclerosis: importance of disease stage on outcome [abstract]. Neurology. 2003;40:A150.
3. Comi G, et al. Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. J Neurol. 2000;247:376-382.
5. Fassas A, et al. Autologous stem cell transplantation in progressive multiple sclerosisdan interim analysis of efficacy. J Clin Immunol. 2000;20:24-30. doi: 10.1023/A:1006686426090.
6. Fassas A, et al. Haematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol. 2002;249:1088-1097. doi: 10.1007/s00415-002-0800-7.
7. Fassas A, Nash R. Multiple sclerosis. Best Pract Res Clin Hematol. 2004;17:247-262. doi: 10.1016/j.beha.2004.04.005.
10. Saccardi R, et al. Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006;12:814-823.
12. Shevchenko Y, Novik A, et al. Three strategies of high dose chemotherapy (HDCT)+autologous stem cell transplantation (ASCT) in autoimmune diseases. Bone Marrow Transplantation. 2004;33(1):346.
13. Shevchenko Y. et al. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis. Experimental Hematology. 2008;36(8):922-928. doi: 10.1016/j.exphem.2008.03.001.
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Aндрей A. Новик1, Алексей Н. Кузнецов1,2, Владимир Я. Мельниченко1, Денис А. Федоренко1, Tатьяна И. Ионова3, Кира А. Курбатова3
1Национальный медико-хирургический центр им. Н.И. Пирогова, Москва, Россия; 2Институт усовершенствования врачей Национального медико-хирургического центра им. Н.И.Пирогова, Москва, Россия; 3Межнациональный центр исследования качества жизни, Санкт-Петербург, Россия
Контакт
А. А. Новик, Национальный медико-хирургический центр им.Н.И. Пирогова, ул. Нижняя Первомайская 70, Москва, 105203, Россия
E-mail: ncrtc04@mail.ru, nqolc@yandex.ru
Одним из новых перспективных подходов к лечению РС является высокодозная иммуносупрессивная терапия с трансплантацией кроветворных стволовых клеток (ВИСТ+ТКСК). ВИСТ+ТКСК является эффективным методом лечения больных с различными формами РС. Целесообразно выделение следующих стратегий ВИСТ+ТКСК: ранняя трансплантация, этапная трансплантация и трансплантация спасения. Концепция ВИСТ+ТКСК открывает большие возможности для интеграции специалистов, занимающихся разработкой новых методов лечения РС, определяя основные направления дальнейших клинических исследований в данной области.
Ключевые слова
рассеянный склероз, аутологичная трансплантация стволовых кроветворных клеток, отдаленные результаты лечения, ранняя трансплантация, этапная трансплантация, трансплантация спасения
Статьи
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[TEXT] => <p class="bodytext">В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев. </p>
<h3>Ключевые слова</h3>
<p> аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз</p>
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Ключевые слова
аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз
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<h3>Keywords </h3>
<p>autologous hematopoietic stem cell transplantation (auto-HSCT), multiple sclerosis </p>
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Евгений П. Евдошенко, Людмила Ст. Зубаровская, Леонид Г. Заславский, Александр А. Скоромец, Сергей М. Алексеев, Юлия А. Станкевич, Наталья А. Тотолян, Борис В. Афанасьев
В данной статье приводятся результаты наблюдения за 23 пациентами с рассеянным склерозом после проведенной аутологичной трансплантации стволовых кроветворных клеток. Обсуждаются риски высокодозной химиотерапии и ее преимущества перед другими методами терапии, а также оптимальный выбор режима кондиционирования и предикторов терапии. Результаты показывают прогрессирование заболевания у большинства пациентов после проведенной терапии через 12-18 месяцев.
Ключевые слова
аутологичная трансплантация стволовых кроветворных клеток (АТСК), рассеянный склероз
Статьи
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[TEXT] => <p>Татьяна И. Ионова, Денис А. Федоренко, Никита Е. Мочкин, Кира А. Курбатова, Андрей А. Новик</p>
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[TEXT] => <p class="bodytext">Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести.
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Tatyana I. Ionova<sup>1</sup>, Denis A. Fedorenko<sup>2</sup>, Nikita E. Mochkin<sup>2</sup>, Kira A. Kurbatova<sup>1</sup>, Andrey A. Novik<sup>2</sup>
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[TEXT] => <p class="bodytext"><sup>1</sup>Multinational Center for Quality of Life Research, St. Petersburg, Russia; <sup>2</sup>Department of Hematology and Cellular Therapy, Pirogov National Medical Surgical Center, Moscow, Russia
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<p class="bodytext"><b>Correspondence</b><br> Tatyana I. Ionova, 195009, Finski per., 9, mailbox 57, St. Petersburg, Russia<br>Phone/Fax: +7 (812) 436-61-12, E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.upmjiDveqfpiv2vy');">qlife@<span style="display:none;">spam is bad</span>rambler.ru</a>
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Татьяна И. Ионова, Денис А. Федоренко, Никита Е. Мочкин, Кира А. Курбатова, Андрей А. Новик
Физическая, психологическая и социальная функции у больных рассеянным склерозом (РС) существеннно нарушены. Это находит отражение в значительном ухудшении качества жизни больных, и степень этого ухудшения вариирует от средней тяжести до критической. Среди большого количества патологических симптомов, сопровождающих течение РС, наиболее частыми, присутствующими у 70 % больных, являются слабость, трудности в ходьбе ("ковыляющая" походка), повышенная чувствительность к теплу, психологические проблемы (чувство тревоги и уныния), ощущение онемения или покалывания на различных участках поверхности тела. Около половины больных с такими симптомами определяют их тяжесть от среднего уровня и выше. Аутологичная трансплантация стволовых клеток (АТСК) больным РС улучшает их физические, психологические и социальные функции. Наиболее отчётливо улучшение качества жизни проявляется в течение первого года после трансплантации. В частности, повышалось количество больных без нарушений показателей качества жизни, а также уменьшение количества больных, имевших до АТСК критическое снижение показателей качества жизни. Качество жизни в целом было улучшено в результате АТСК у подавляющего количества больных РС как за счёт сужения спектра патологических симптомов, так и уменьшения их тяжести.
Статьи
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[TEXT] => <p class="bodytext">Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF. <br /><br />Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз. <br /><br />Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом.
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Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз.
Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом.
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[TEXT] => <p class="bodytext">Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology of Russian Academy of Medical Sciences, Siberian Branch, Novosibirsk, Russia
</p><br>
<p class="bodytext"><b>Correspondence</b><br> Elena Chernykh, Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology RAMS SB, Yadrintsevskaya str., 14, Novosibirsk, 630099, Russia
<br>Phone: +7(383)2360329; Fax: +7(383)2227028; E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.gx_pefDqemp2vy');">ct_lab@<span style="display:none;">spam is bad</span>mail.ru</a>
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Correspondence
Elena Chernykh, Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology RAMS SB, Yadrintsevskaya str., 14, Novosibirsk, 630099, Russia
Phone: +7(383)2360329; Fax: +7(383)2227028; E-mail: ct_lab@mail.ru
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[TEXT] => <p class="bodytext">Regulation of the immune response seems to be a promising strategy for a successful central nervous system (CNS) repair, and macrophages are considered to be prospective candidates for cell therapy. Using low serum conditions we generated human anti-inflammatory M2-like macrophages from peripheral blood monocytes and compared these cells (termed Mφ3) with “standard” pro-inflammatory Mφ1 and anti-inflammatory Mφ2, generated in the presence of GM-CSF and M-CSF. We focused primarily on the differences in T-cell stimulatory activity and production of various cytokines, chemokines, and growth factors. Low serum conditions had no negative impact on macrophage yield, the largest of which was for Mφ3. We showed that Mφ3 more closely resembled Mφ2 than Mφ1. Mφ2 and particularly Mφ3, but not Mφ1 expressed relatively low levels of CD86 and failed to stimulate T-cell proliferation. In contrast to pro-inflammatory Mφ1, unstimulated Mφ3 produced significantly lower levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18, IL-12) and Th1/Th2-cytokines (IFN-γ, IL-2, IL-4) coupled with a higher IL-10 level. Moreover, concentrations of IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in Mφ-3 supernatants were lower not only when compared to Mφ1, but also to Mφ2 cultures. Like Mφ1 and Mφ2, Mφ3 was capable of producing neurotrophic- (BDNF, IGF-1), angiogenic- (VEGF), and other growth factors (EPO, G-CSF, FGF-basic, EGF) with neuroprotective and regenerative activity. In fact, IGF-1 production by Mφ-3 exceeds secretion of this factor by Mφ-1 and Mφ-2 by more than 25 fold. Thus, generated Mφ-3 represented M2-like macrophages with high regenerative potential.
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Елена Р. Черных, Екатерина Я. Шевела, Людмила В. Сахно, Марина А. Тихонова, Ярослав Л. Петровский, Александр А. Останин
Регуляция иммунного ответа представляется перспективной стратегией в области восстановления повреждений центральной нервной системы (ЦНС). При этом важная роль в качестве кандидатов для клеточной терапии отводится макрофагам. Используя культуральные условия с низким содержанием сыворотки, мы разработали протокол генерации противовоспалительных, М2-подобных, макрофагов из моноцитов периферической крови и сравнили эти клетки (обозначенные как М3) со «стандартными» провоспалительными (Mφ1) и противовоспалительными (Mφ2) макрофагами, генерированными, соответственно, в присутствии GM-CSF и M-CSF.
Основное внимание было прежде всего сосредоточено на способности макрофагов стимулировать пролиферацию Т-клеток, а также продукцию макрофагами различных цитокинов, хемокинов и ростовых факторов. Дефицит сывороточных факторов не сказывался негативным образом на количестве генерированных макрофагов. Напротив, наибольший выход клеток наблюдался в культурах M3. По своим свойствам M3 макрофаги больше походили на Mφ2, чем на Mφ1. Так, в отличие от Mφ1, макрофаги Mφ2 и, особенно, M3 отличались относительно низким уровнем экспрессии CD86 и не стимулировали пролиферативный ответ Т-клеток. В противоположность провоспалительным Mφ1 нестимулированные M3 продуцировали гораздо меньшие уровни провоспалительных (IL-1β, TNF-α, IL-6, IL-18, IL-12) и Th1/Th2 цитокинов (IFN-γ, IL-2, IL-4), вместе с тем - более высокий уровень IL-10. Более того, концентрации IL-1β и провоспалительных хемокинов IL-8 и MCP-1 в супернатантах M3 были снижены не только по сравнению с Mφ1, но также и с Mφ2 культурами. Подобно Mφ1 и Mφ2, М3 обладали способностью продуцировать нейротрофические (BDNF, IGF-1), ангиогенные (VEGF) и другие ростовые факторы с нейропротективной и регенераторной активностью (EPO, G-CSF, FGF-basic, EGF). При этом уровень продукции IGF-1 макрофагами 3-его типа превышал секрецию этого фактора Mφ1 и Mφ2 более чем в 25 раз.
Суммируя полученные данные, можно заключить, что генерируемые M3 клетки представляют M2-подобные макрофаги с высоким регенераторным потенциалом.
Другие темы
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[TEXT] => <p class="bodytext">Тяжёлые формы реакции «трансплантат против хозяина» (РТПХ) являются основной причиной заболеваемости и смертности у длительно живущих больных после трансплантации аллогенных гемопоэтических клеток. <br /><br />Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации<br> Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение<br> В-клеточных антител и иматиниба (ингибитора тирозинкиназы).<br /><br />Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы.
</p>
<h3>Ключевые слова</h3>
<p> хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат</p>
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[TEXT] => Тяжёлые формы реакции «трансплантат против хозяина» (РТПХ) являются основной причиной заболеваемости и смертности у длительно живущих больных после трансплантации аллогенных гемопоэтических клеток.
Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации
Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение
В-клеточных антител и иматиниба (ингибитора тирозинкиназы).
Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы.
Ключевые слова
хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат
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[TEXT] => <p class="bodytext">Severe chronic graft versus host disease (GVHD) is the main factor for late morbidity and mortality in long-term survivors after allogeneic hematopoietic cell transplantation. The only established treatment of chronic graft versus host disease is the use of high dose corticosteroids. However, multiple different treatment approaches have been evaluated mostly in small phase 2 studies. These included calcineurin inhibitors for blocking T-cell activation, classical cytotoxic drugs, like methotrexate or azathioprine, as well as immunomodulatory substances like cytokine inhibitors or thalidomide. More recently novel treatment approaches have been evaluated. These include the use of B-cell antibodies and the tyrosine kinase inhibitor imatinib. Furthermore treatment options beyond mere immunosuppression that aim to induce tolerance are currently under investigation. These include extra-corporal photopheresis and treatment with inhibitors of the mammalian target of rapamycin. This review will discuss these different treatment approaches.</p>
<h3>Keywords</h3>
<p> chronic GVHD, calcineurin inhibitors, mTOR, extracorporal photopheresis, immunomodulatory drugs, steroids, methotrexate
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Михаэл Шлёнинг
Тяжёлые формы реакции «трансплантат против хозяина» (РТПХ) являются основной причиной заболеваемости и смертности у длительно живущих больных после трансплантации аллогенных гемопоэтических клеток.
Единственный общепризнанный метод лечения РТПХ подразумевает применение высоких доз кортикостероидов. Однако другие многочисленные подходы были апробированы лишь в непродолжительные сроки на 2-й фазе клинических испытаний. Они касались ингибиторов кальциневрина для блокирования активации
Т-клеток; классических цитостатиков, например, метотрексата и азатиоприна; а также иммуномодулирующих препаратов, например, ингибиторов цитокинов или талидомида. Совсем недавно были испытаны новые лечебные подходы. Среди них применение
В-клеточных антител и иматиниба (ингибитора тирозинкиназы).
Помимо этого, сейчас находятся на испытании другие лечебные методы, не исключительно иммуносупрессивного характера, но также направленные на индукцию толерантности. Для этого используют экстракорпоральный фотоферез и ингибиторы TOR (молекул-мишеней для рапамицина). В этом обзоре обсуждаются подобные лечебные подходы.
Ключевые слова
хроническая РТПХ, ингибиторы кальциневрина, mTOR (клеточные мишени рапимицина у позвоночных), экстракорпоральный фотоферез, иммуномодулирующие препараты, стероиды, метотрексат
Другие темы
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<p> лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток</p>
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Ключевые слова
лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток
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<h3>Keywords</h3>
<p> leukemia, pediatric oncology, T cells, immunotherapy, adoptive T cell transfer
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Keywords
leukemia, pediatric oncology, T cells, immunotherapy, adoptive T cell transfer
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Клаудиа Россиг
Трансплантация аллогенных гемопоэтических клеток (алло ТГСК) вносит существенный вклад в лечение детей, больных лейкозом с высокой вероятностью рецидива. Роль и влияние реакции «трансплантат против лейкоза» (РТПЛ) на течение лейкоза у детей при аллогенной трансплантации не имеет детального объяснения. Эффективность в этих ситуациях основывается главным образом на связи клинических признаков наличия аллореактивности со стабильным полным донорским химеризмом и выживаемостью пациентов на фоне отсутствия рецидивов. Терапевтические подходы, специально направленные на усиление аллореактивности донорских клеток посредством ослабления иммуносупрессивных воздействий или введения лимфоцитов донора, ограничены возможностью развития реакции «трансплантат против хозяина» (РТПХ). Поэтому важной задачей на путях более широкого внедрения трансплантации аллогенных гемопоэтических стволовых клеток для лечения лейкозов у детей является разработка лечебной стратегии, которая позволит усилить РТПЛ и одновременно избежать РТПХ. Одна из таких стратегий подразумевает генетическую модификацию специфических рецепторов Т-клеток или НК-клеток, которая позволила бы распознавать антигены, ассоциированные с лейкозом. Современные разработки сфокусированы на дальнейшей оптимизации in vivo функциональной активности Т-клеток, в том числе их расселения («хоминга») в лейкозном микроокружении, длительного пребывания и способности к специфической реактивации в этой среде.
Ключевые слова
лейкоз, детская онкология, Т-клетки, иммунотерапия, адоптивный перенос Т-клеток
Другие темы
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[TEXT] => <h3><a target="_blank" href="http://www.science-connections.com/video/node/81"><span style="font-size: 16pt; color: #0000ff;">Видеолекция</span></a></h3>
<p class="bodytext">
Лекция начинается историческими сведениями о трансплантации гемопоэтических стволовых клеток (ТГСК), а также о первом клиническом опыте алло-ТГСК с применением аллотрансплантата, лишенного Т-лимфоцитов. Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ).
</p>
<p class="bodytext">
Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам <span lang="EN-US">CD</span><span lang="RU">8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.</span>
</p>
<p class="bodytext">
Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (<span lang="EN-US">CD</span><span lang="RU">25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением </span><span lang="EN-US">CD</span><span lang="RU">6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по </span><span lang="EN-US">HLA</span><span lang="RU">-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. </span>Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение <i><span lang="EN-US">in</span><span lang="EN-US"> </span></i><i><span lang="EN-US">vitro</span></i><span lang="EN-US"> </span><span lang="RU">и </span><span lang="EN-US">i<i>n</i></span><i><span lang="EN-US"> </span></i><i><span lang="EN-US">vivo</span><span lang="EN-US"> </span></i><span lang="RU">в целях профилактики развития лимфом и их контроля в клинических условиях.</span>
</p>
<p class="bodytext">
Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов.
</p>
<p class="bodytext">
<strong>Ключевые слова</strong><br>
<span lang="RU"> хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, </span><span lang="EN-US">MHC</span><span lang="RU">-антигены, </span><span lang="EN-US">HLA</span><span lang="RU">-несовместимость, иммунная толерантность, антивирусный иммунитет</span>
</p>
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Лекция начинается историческими сведениями о трансплантации гемопоэтических стволовых клеток (ТГСК), а также о первом клиническом опыте алло-ТГСК с применением аллотрансплантата, лишенного Т-лимфоцитов. Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ).
Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам CD8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.
Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (CD25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по HLA-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением CD6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по HLA-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение in vitro и in vivo в целях профилактики развития лимфом и их контроля в клинических условиях.
Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов.
Ключевые слова
хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, MHC-антигены, HLA-несовместимость, иммунная толерантность, антивирусный иммунитет
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[TEXT] => <p class="bodytext">Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Germany
</p><br>
<p class="bodytext"><b>Correspondence</b><br> Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81337 Munich, Germany
<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.Lerw2OspfDqih2yrm1qyirglir2hi');">Hans.Kolb@<span style="display:none;">spam is bad</span>med.uni-muenchen.de<br /></a>
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[TEXT] => Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Germany
Correspondence
Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81337 Munich, Germany
E-mail: Hans.Kolb@med.uni-muenchen.de
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[TEXT] => <h3><span style="font-size: 16pt;"><a target="_blank" href="http://www.science-connections.com/video/node/81"><span style="color: #0000ff;">V</span></a><span style="color: #0000ff;">ideolection</span></span></h3>
<p class="bodytext">
The lecture begins by describing the historical features of hematopoietic stem cell transplantation (HSCT), followed by the first clinical experiences with T cell-depleted allografts. A concept of adoptive immune therapy is proposed for chimeric organisms after T-cell depleted grafting, aiming for an increased graft-versus-leukemia (GvL) effect.<br>
<br>
The efficiency of donor lymphocyte transfusions (DLT) was extensively tested, being more expressed in chronic myeloid leukemia (CML). The intensity of graft-versus-host disease (GvHD), generally correlates with GvL, and is thus associated with an anti-leukemic response. Hence, DLT is a useful means of achieving long-term molecular remission in CML, as confirmed by EMBT studies.<br>
<br>
The clinical efficiency of post-transplant adoptive immunotherapy was shown in EBMT trials. This effect is more pronounced in CML, since malignant myeloid precursors supposedly produce antigen-presenting dendritic cells (DCs). Within the general mechanism of GvHD, a 'cytokine storm' may promote this type of immune response. DCs present MHC antigens to the CD8+ effector cells, thus providing them with a 'license to kill'. A clinical protocol was introduced on this basis, using a combined therapeutic schedule including GM-CSF and carefully timed DLT procedures.<br>
<br>
A theory of evolving immune tolerance is also discussed, encompassing specific interactions between host DCs and donor CD25+ regulatory T cells. A concept of central (thymus-dependent) tolerance is developed, primarily for children undergoing therapy. Haploidentical transplants are therefore considered with respect to increased NK cell production, especially in acute lymphoblastic leukemia (ALL). A possible role of HLA mismatches and the association between chronic GvHD (cGvHD) and long-term GvL effects is discussed, such as the favorable role of cGvHD in CML, unlike ALL. Fractionation of mobilized peripheral blood cells with CD6+ cell depletion proved to be a useful immune modulation tool. <br>
<br>
The significance of HLA mismatches is discussed in connection with modulation of NK activity; this is presumably dependent upon specific interactions between homozygous and heterozygous immune cells, either of donor or recipient origin. <br>
<br>
Antiviral immunity is also discussed: in particular, generation of anti-EBV-specific cells and their in vitro and in vivo expansion, aiming for potential lymphoma prevention and control in clinical settings. <br>
<br>
Meanwhile, GvL is postulated to proceed either via naïve or memory T cell populations, as illustrated by cases of double cord blood transplantations. The possible mechanisms of graft-graft interactions are discussed.<br>
<br>
Hence, adoptive immune therapy in chimeric patients should be regarded as an effective accessory tool for eradication of leukemic cells – at least in some types of leukemia.<br>
</p>
<h3>Keywords</h3>
<p>
chronic myeloid leukemia, adoptive immune therapy, dendritic cells, T cells, HLA mismatch, immune tolerance, antiviral immunity
</p>
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[TEXT] => Videolection
The lecture begins by describing the historical features of hematopoietic stem cell transplantation (HSCT), followed by the first clinical experiences with T cell-depleted allografts. A concept of adoptive immune therapy is proposed for chimeric organisms after T-cell depleted grafting, aiming for an increased graft-versus-leukemia (GvL) effect.
The efficiency of donor lymphocyte transfusions (DLT) was extensively tested, being more expressed in chronic myeloid leukemia (CML). The intensity of graft-versus-host disease (GvHD), generally correlates with GvL, and is thus associated with an anti-leukemic response. Hence, DLT is a useful means of achieving long-term molecular remission in CML, as confirmed by EMBT studies.
The clinical efficiency of post-transplant adoptive immunotherapy was shown in EBMT trials. This effect is more pronounced in CML, since malignant myeloid precursors supposedly produce antigen-presenting dendritic cells (DCs). Within the general mechanism of GvHD, a 'cytokine storm' may promote this type of immune response. DCs present MHC antigens to the CD8+ effector cells, thus providing them with a 'license to kill'. A clinical protocol was introduced on this basis, using a combined therapeutic schedule including GM-CSF and carefully timed DLT procedures.
A theory of evolving immune tolerance is also discussed, encompassing specific interactions between host DCs and donor CD25+ regulatory T cells. A concept of central (thymus-dependent) tolerance is developed, primarily for children undergoing therapy. Haploidentical transplants are therefore considered with respect to increased NK cell production, especially in acute lymphoblastic leukemia (ALL). A possible role of HLA mismatches and the association between chronic GvHD (cGvHD) and long-term GvL effects is discussed, such as the favorable role of cGvHD in CML, unlike ALL. Fractionation of mobilized peripheral blood cells with CD6+ cell depletion proved to be a useful immune modulation tool.
The significance of HLA mismatches is discussed in connection with modulation of NK activity; this is presumably dependent upon specific interactions between homozygous and heterozygous immune cells, either of donor or recipient origin.
Antiviral immunity is also discussed: in particular, generation of anti-EBV-specific cells and their in vitro and in vivo expansion, aiming for potential lymphoma prevention and control in clinical settings.
Meanwhile, GvL is postulated to proceed either via naïve or memory T cell populations, as illustrated by cases of double cord blood transplantations. The possible mechanisms of graft-graft interactions are discussed.
Hence, adoptive immune therapy in chimeric patients should be regarded as an effective accessory tool for eradication of leukemic cells – at least in some types of leukemia.
Keywords
chronic myeloid leukemia, adoptive immune therapy, dendritic cells, T cells, HLA mismatch, immune tolerance, antiviral immunity
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Ханс-Йохем Кольб
Видеолекция
Лекция начинается историческими сведениями о трансплантации гемопоэтических стволовых клеток (ТГСК), а также о первом клиническом опыте алло-ТГСК с применением аллотрансплантата, лишенного Т-лимфоцитов. Предлагается концепция адоптивной иммунотерапии при наличии химеризма после ТГСК с удалением Т-клеток из трансплантата, с целью усилить эффект «трансплантат против лейкоза» (ТПЛ).
Эффективность трансфузий донорских лимфоцитов (ТДЛ) проверяли в большом числе работ, и показано, что этот эффект более выражен при лечении хронического миелоидного лейкоза (ХМЛ). Интенсивность реакции «трансплантат против хозяина» (РТПХ), в целом, коррелирует с реакцией ТПЛ, будучи ассоциированной с клиническим ответом при лечении лейкоза. Таким образом, ТДЛ, как вариант адоптивной иммунотерапии, является эффективным способом достижения долгосрочной молекулярной ремиссии при ХМЛ, что подтверждено клиническими исследованиями Европейской группы по трансплантации костного мозга. Большая выраженность подобного эффекта при ХМЛ, возможно, связана с дифференцировкой злокачественных миелоидных предшественников в антиген-презентирующие дендритные клетки (ДК). В рамках механизмов РТПХ, «цитокиновая буря» может способствовать развитию иммунного ответа такого типа. ДК осуществляют презентацию антигенов МНС клеткам-эффекторам CD8+, тем самым предоставляя им «лицензию на убийство». На этом основан клинический протокол с применением комбинированной терапии, включающий ГМ-КСФ и ТДЛ, которые используются в определенные временные периоды.
Обсуждается также теория развития иммунологической толерантности, касающаяся специфических взаимодействий между ДК организма-реципиента и регуляторными Т-клетками (CD25+). Разработана концепция центральной (тимус-зависимой) толерантности, прежде всего – для больных детского возраста. В связи с этим, гаплоидентичные трансплантации рассматриваются в плане повышения продукции натуральных киллеров (НК-клеток), особенно при остром лимфобластном лейкозе (ОЛЛ). Обсуждается возможное клиническое значение несовместимости по HLA-антигенам и взаимосвязи между хронической РТПХ (хРТПХ) и долгосрочными эффектами ТПЛ. Предполагается позитивная роль хРТПХ в прогнозе при ХМЛ, в отличие от ситуации с ОЛЛ. Фракционирование мобилизованных стволовых клеток периферической крови с удалением CD6+ клеток также оказалось эффективным средством иммуномодуляции при ТГСК. Значимость расхождений по HLA-антигенам обсуждается в связи с модуляцией активности НК-клеток, предположительно, зависящей от специфических взаимодействий между гомо- и гетерозиготными иммунными клетками, происходящими от донора или реципиента. Обсуждаются также вопросы антивирусных иммунных реакций, в особенности – генерация клеток, специфичных против вируса Эпштейна-Барр и их размножение in vitro и in vivo в целях профилактики развития лимфом и их контроля в клинических условиях.
Рассматриваются варианты развития эффекта ТПЛ через «необученные» Т-клеточные популяции или Т-клетки памяти, что иллюстрируется клиническими данными по двойной трансплантации клеток пуповинной крови. Обсуждаются также взаимодействия между трансплантатами. Таким образом, адоптивная иммунотерапия у больных, находящихся в состоянии химеризма, должна рассматриваться в качестве эффективного дополнительного средства устранения лейкозных клеток, по крайней мере, при некоторых типах лейкозов.
Ключевые слова
хронический миелоидный лейкоз, адоптивная иммунотерапия, дендритные клетки, Т-лимфоциты, MHC-антигены, HLA-несовместимость, иммунная толерантность, антивирусный иммунитет
Другие темы
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Мальте фон Бонин, Мартин Вермке, Уве Платцбекер, Йорген Радке, Нона Шайеги, Сузанна Гретцингер, Конрад Хойхель, Кристина Хелиг, Марк Шмитц, Герхард Энингер, Йоханнес Шетелиг, Марти Борнхойзер
Первичная терапия острой болезни «трансплантат против хозяина (оРТПХ) II-IV степени все еще основана на применении кортикостероидов (например – преднизолона) в дозах 1-2 мг/кг. Обычно исследователи сочетают этот подход с терапевтическими дозами ингибиторов кальцинейрина, которые используются в целях профилактики. Больные, не отвечающие на лечение стероидами в течение 5-7 дней, или пациенты с прогрессированием заболевания в течение 72 часов представляют собой группу высокого риска, требующую дальнейшей эскалации иммуносупрессии. Фармакологическое лечение второй линии определяется, в основном, тактикой, применяемой в данном центре, или индивидуальными решениями, поскольку отсутствует стратегия повышения выживаемости, основанная на контролируемом проспективном клиническом испытании. Выявлены препараты, показавшие эффективность по данным II фазы клинических испытаний: микофенолят мофетил, метотрексат, пентостатин, ингибиторы mTOR, антитела, направленные против ФНО-альфа или ИЛ-2, а также моноклональные или поликлональные антитела против Т-клеток. К немедикаментозным средствам лечения относятся: экстракорпоральный фотоферез и инфузия аллогенных мезенхимных стромальных клеток. При большинстве воздействий более раннее лечение (напр., в течение 2 недель) связано с лучшим исходом. Однако общая эффективность и токсичность при большинстве подходов не являются удовлетворительными. Дальнейшие разработки состоят в использованиии регуляторных Т-клеток и более нацеленные методы с применением малых молекул, действующих на специфические сигнальные пути в антиген-презентирующих и эффекторных клетках.