ISSN 1866-8836
Клеточная терапия и трансплантация

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Volume 8, number 4
12/23/2019
Volume 8, number 4
Editor-in-Chief
Afanasyev B. V. (St. Petersburg, Russia)
Co-Editors-in-Chief
Wagemaker G. (Rotterdam, Netherlands)
Zander A. R. (Hamburg, Germany)
Deputy Editor
Fehse B. (Hamburg, Germany)
Managing Editor
Chukhlovin A. B. (St. Petersburg, Russia)
Editorial Board
Aleynikova O. V. (Minsk, Republic of Belarus)
Borset M. (Trondheim, Norway)
Chechetkin A. V. (St. Petersburg, Russia)
Fibbe W. (Leiden, Netherlands)
Galibin O. V. (St. Petersburg, Russia)
Hölzer D. (Frankfurt a.M., Germany)
Klimko N. N. (St. Petersburg, Russia)
Kolb H.-J. (München, Germany)
Kröger N. (Hamburg, Germany)
Kulagin A. D. (St. Petersburg, Russia)
Lange C. (Hamburg, Germany)
Mamaev N. N. (St. Petersburg, Russia)
Mikhailova N. B. (St. Petersburg, Russia)
Moiseev I. S. (St. Petersburg, Russia)
Nagler A. (Tel-Aviv, Israel)
Nemkov A. S. (St. Petersburg, Russia)
Paramonov I. V. (Kirov, Russia)
Roumiantsev A. G. (Moscow, Russia)
Savchenko V. G. (Moscow, Russia)
Smirnov A. V. (St. Petersburg, Russia)
Uss A. L. (Minsk, Republic of Belarus)
Zubarovskaya L. S. (St. Petersburg, Russia)
In this Issue
The article by Dr. M. Khrustalev et al. concerns scientometry of 5 major Russian centers performing hematopoietic stem cell transplantation (HSCT). Common parameters, e.g., citation rates and collective Hirsch index were used. SciVal platform is recommended for better comparisons with the leading HSCT centers in the world.

A comprehensive mini-review by Prof. A. Zander provides novel data on mesenchymal stromal cells (MSC), with respect to their applications in practical medicine, evidence-based efficiency in various diseases, and prospects of its wider use in future.

Another review by Dr. S. Kulemzin et al. considers potential antigenic targets on the prostate cancer cells for prospective CAR-T cell therapy. The authors range them by their specificity to prostatic malignancies and expression grade.

Professor A. Kohlschütter presents his experience of enzyme replacement therapy of the CLN2 disease, a fatal lipid storage disorder. Its clinical course could be sufficiently improved by injections of the normal enzyme into the brain ventriculi.

A clinically sound article by Dr. P. Kozhokar deals with efficiency of repeated HSCT after failing engraftment of the 1st transplant and in relapsing malignancies. The authors show some benefits of this approach in terms of overall and relapse-free survival.

Clinical efficiency of immune checkpoint inhibitors in Hodgkin’s lymphoma is assessed in pediatric setting by Dr. A. Kozlov et al. They have shown sufficient clinical remission rates after Nivolumab therapy in refractory/resistant cases.

The issues of microbiota changes caused by heavy antibiotic treatment during HSCT procedure are discussed in original study by Dr. A. Spiridonova et al. including depletion of commensal microbes within 1st month posttransplant, and Klebsiella expansion at later terms.

A clinical case of the fatal parvovirus-associated hemorrhagic enteritis in a septic patient post-HSCT is presented by Dr. O. Goloshchapov et al. The case is well verified, however, the parvovirus was not traced from the beginning of this condition.

Under the Rehabilitation section, we publish an article by Dr. F. Terentiev et al. which proposes rational and individualized physical exercises for the children subjected to HSCT. These training programs have resulted into better quality of life in this group of pediatric patients.

A fundamental approach was used by Prof. S. Chechelnitskaya et al. who have detected some disturbances of postural stability in the children treated for cerebral malignancies. Oculomotor muscles proved to cause these functional alterations of eye movements.

Professor A. Yaremenko et al. have described experimental results which show high efficiency of polycaprolacton scaffolds, applied for closure and accelerated repair of maxillar defects occurring after tooth extraction.

The beneficiary effects of mesenchymal stem cells (MSC) are reported by Dr. Khademi et al. who have shown a significant alleviation of experimental anosmia and restoration of olfactory cells after injection of fat-derived MSCs.

An essay concerning nearest perspectives of gene editing and therapy is presented by Dr. K. Zakurdaeva who monitors the problems with development and implication issues of appropriate commercial gene-engineered products.

General topics

Scientometric indices of Russian centers active in oncology/hematology research

Maksim B. Khrustalev, Artem V. Tishkov, Natalia Yu. Turbina, Anna A. Maksimova

Review articles

Clinical studies

Nivolumab in pediatric Hodgkin's lymphoma

Andrey V. Kozlov, Ilya V. Kazantzev, Tatyana V. Iukhta, Polina S. Tolkunova, Darya A. Zvyagintseva, Asmik G. Gevorgian, Anton V. Malorodov, Kirill V. Lepik, Yury R. Zalyalov, Alexander N. Shvetsov, Anna V. Botina, Vadim V. Baykov, Elena V. Morozova, Yury A. Punanov, Natalya B. Mikhailova, Ludmila S. Zubarovskaya, Boris V. Afanasyev

Efficiency of second allogeneic HSCT in the children with acute leukemias with relapses after first transplantation

Polina V. Kozhokar1, Olesya V. Paina1, Anastasia S. Frolova1, Zhemal Z. Rakhmanova1, Anastasia S. Borovkova1, Elena V. Semenova1, Anna A. Osipova1, Kirill A. Ekushov1, Olga A. Slesarchuk1, Varvara N. Ovechkina1, Elena V. Babenko1, Alina A. Vitrishchak1, Boris I. Smirnov2, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1

Common bacterial cultures from oral mucosa after hematopoietic stem cell transplantation: dependence on the patient characteristics and therapeutic factors

Alexei B. Chukhlovin1, Anna A. Spiridonova2, Irina B. Baranova3, Artur P. Grigoriants3, Maria D. Vladovskaya1, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1

Clinical case

Haemorrhagic enteritis associated with parvovirus B19 following hematopoietic stem cell transplantation: a case report and literature data

Oleg V. Goloshchapov1, Natalia D. Ventslovayte1, Ruslana V. Klementeva1, Alexander N. Shvetsov1, Aleksandr A. Shcherbakov1, Maria O. Goloshchapova1, Vadim E. Karev2, Boris V. Afanasyev1

Rehabilitation

Effects of motor exercises upon life quality of adolescents subjected to hematopoietic stem cell transplantation

Alla A. Potapchuk1, Alisa G. Volkova1, Fedor V. Terentiev2, Irina G. Terentieva2, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1

Sensory conflict as a possible reason for disturbed postural stability in the children treated for cancer

Serafima M. Chechelnitskaia, Vladimir N. Kasatkin, Marina A. Shurupova, Irina D. Borodina, Yurij V. Sarajkin, Aleksandr F. Karelin, Dmitrij V. Skvorcov, Aleksandra V. Baerbakh, Daria V. Zhuk, Vladislav A. Nikulin

Experimental studies

Game of genomes: to be continued

Kristina A. Zakurdaeva

Adipose-derived mesenchymal stem cells (ASCs) transplantation restored olfactory function in anosmic rats

Bijan Khademi1,2, Zohreh Zandifar2, Ahmad Monabati3, Nooshafarin Chenari4, Abbas Ghaderi4,5, Mahboobeh Razmkhah4

Experimental study of polymer-based scaffolds promoting bone tissue repair in oroantral communication

Аndrey I. Yaremenko1, Anna V. Lysenko1, Elizaveta A. Ivanova1, Galina U. Ukina4, Alexander D. Vilesov3, Marina A. Chibisova5, Anna A. Zubareva2, Оleg V. Galibin3

Supplement 1

Indications for hematopoietic stem cell transplantation

Editor: Prof. Dr. Boris V. Afanasyev

Ksenia S. Afanasyeva, Maria V. Barabanshchikova, Sergey N. Bondarenko, Tatyana A. Bykova, Julia Yu. Vlasova, Asmik G. Gevorgian, Irina K. Golubovskaya, Elena I. Darskaya, Yury R. Zalyalov, Darya A. Zvyagintseva, Ludmila S. Zubarovskaya, Maria O. Ivanova, Ilya V. Kazantsev, Olga B. Kalashnikova, Andrey V. Kozlov, Elena V. Kondakova, Vladislav O. Korolenko, Olga V. Kudyasheva, Alexander D. Kulagin, Elena E. Lepik, Kirill V. Lepik, Inna V. Markova, Irina A. Mikhailova, Natalya B. Mikhailova, Ivan S. Moiseev, Elena V. Morozova, Anna A. Osipova, Olesya V. Paina, Olga V. Pirogova, Alexey Yu. Polushin, Marina O. Popova, Valentina V. Porunova, Yury A. Punanov, Elena V. Semenova, Anna G. Smirnova, Olesya V. Smykova, Polina S. Tolkunova, Lyudmila V. Fedorova, Nikolay Yu. Tcvetkov, Ivan V. Tsygankov, Tatyana V. Yukhta

General topics

Scientometric indices of Russian centers active in oncology/hematology research

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Maksim B. Khrustalev, Artem V. Tishkov, Natalia Yu. Turbina, Anna A. Maksimova

Pavlov University, St. Petersburg, Russia

The aim of this survey was to perform scientometric evaluation of the major Russian institutions conducting research in the field of oncology and hematology, relying primarily on the common quality indicators and impact of the research results, to аssess their position in the scientific topic clusters (TC) according to international citation databases.

Materials and methods

A comparison was made between five organizations conducting research in the field of oncology and hematology, i.e., four National Medical Research Centers (NMRCs), and Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation (R. Gorbacheva Institute) which is a part of I. Pavlov St. Petersburg State Medical University, using the following scientometric indices: citation, collective Hirsch index, as well as the productivity of research determined as relative share of publications in the scientific TC, as well as Field-weighted Citation Impact, using the SciVal platform. The list of publications was limited to keywords defining the field of research of these organizations.

Results

Comparative evaluation of research publication activity in oncohematology has shown the leading position of R. Gorbacheva Institute, as a part of I. Pavlov St. Petersburg State Medical University, which was not included into the NMRCs network. Its rating was only slightly lower than the indices of N. Petrov National Medical Research Center of Oncology and N. Blokhin National Medical Research Center of Oncology. The overall indices of the citation impact based on SciVal analytic platform assessed for R. Gorbacheva Institute are at a level compared to the figures for world publications in the selected topic clusters.

Conclusion

Efficiency of clinical research at an educational institution, evaluated as the number of highly cited publications proved to be not lower, but sometimes even higher than in specialized research institutions working in the field. Appropriate publishing activity evaluated by the SciVal system showed that the funding authorities providing research financiation should recognize R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation at the Pavlov University as a perspective university-based platform for research in relevant areas, along with existing specialized scientific institutions.

Keywords

Hematology, oncology, national medical research centers, medical university, scientometric indexes, bibliometry, citation analysis.

Review articles

Mesenchymal stroma cells (MSCs) in Regenerative Medicine: an update

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Axel R. Zander

University of Hamburg, Germany

Mesenchymal stroma cells (MSCs) have anti-inflammatory, anti-apoptotic and immunomodulating properties, and they have, therefore, been explored in the treatment of autoimmune and chronic inflammatory diseases during the last two decades. MSCs have reached regulatory approval in several countries for the treatment of Acute Graft-versus-Host Disease and for Crohn’s disease. Results in several other diseases like Lupus, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Spinal cord injury look promising.

Uncritical, direct to consumer sales of unapproved stem cell treatments by private entrepreneurs cloud the field of MSC research and jeopardize the establishment of MSC treatment in the armamentarium of Medicine. Several more years are necessary for a full evaluation of this new treatment modality in several indications.

Keywords

Mesenchymal stromal cells, immune effects, medical applications.

Review articles

Prostate cancer surface targets for CAR T cell therapy or metastatic prostate cancer in the CAR T cell era: My kingdom for the target!

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Sergey V. Kulemzin1, Andrey A. Gorchakov1,2, Aleksandr V. Taranin1,2

1 Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2 Novosibirsk State University, Novosibirsk, Russia

Despite the progress achieved in target, chemo-, and radiotherapy, treatment options for patients with late-stage metastatic castration-resistant prostate cancer are presently very limited. Use of dendritic cell-based vaccines exemplified by sipuleucel-T appears is rarely curative and is effective in only a fraction of such patients. Given the success of CAR T cell therapy in the field of B cell malignancies, significant efforts have been made to adapt this powerful technology to the problem of metastatic prostate cancer. Availability of unique prostate cancer surface targets for CAR T cells has thereby become a pressing issue in the field of CAR design. Ideally, such targets should be absent from normal cells or tissues, be present on all prostate cancer cells across all patients, and be indispensable for the survival of cancer cells. In reality, however, none of the prostate cancer-associated surface markers described to date are matching such description. Here, we catalogue the list of tested as well as prospective surface antigens to be used as targets for CAR T cell therapy, and discuss the aspects of their safety and potential efficacy.

Keywords

Metastatic prostate cancer, immunotherapy, chimeric antigen receptor, CAR T cells.

Clinical studies

Nivolumab in pediatric Hodgkin's lymphoma

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Andrey V. Kozlov, Ilya V. Kazantzev, Tatyana V. Iukhta, Polina S. Tolkunova, Darya A. Zvyagintseva, Asmik G. Gevorgian, Anton V. Malorodov, Kirill V. Lepik, Yury R. Zalyalov, Alexander N. Shvetsov, Anna V. Botina, Vadim V. Baykov, Elena V. Morozova, Yury A. Punanov, Natalya B. Mikhailova, Ludmila S. Zubarovskaya, Boris V. Afanasyev

Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia

Immune checkpoint inhibitors (ICIs) are rather efficient in classical Hodgkin's lymphoma (cHL). Pembrolizumab (pembro) is approved in children and demonstrates high response rates with acceptable toxicity. The role of nivolumab (nivo) in pediatric cHL is only to be elucidated. The aim of the presented study was to assess safety and efficiency of nivo in this age group with relapsed or refractory (R-R) cHL. Twenty-one pediatric heavily pre-treated patients 9-18 years old received nivo-based therapy. Overall response was registered in 86% (complete response – 57% and partial response – 29%). Three-year overall survival (OS) and progression free survival (PFS) were 95% and 29%, respectively. Only 1 clinically significant adverse effect (AE) of nivo was registered in the study (autoimmune thyroiditis). We did not observe any unacceptable toxicity of nivo.

Keywords

Children, Hodgkin's lymphoma, relapsed, refractory, nivolumab.

Clinical studies

Efficiency of second allogeneic HSCT in the children with acute leukemias with relapses after first transplantation

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Polina V. Kozhokar1, Olesya V. Paina1, Anastasia S. Frolova1, Zhemal Z. Rakhmanova1, Anastasia S. Borovkova1, Elena V. Semenova1, Anna A. Osipova1, Kirill A. Ekushov1, Olga A. Slesarchuk1, Varvara N. Ovechkina1, Elena V. Babenko1, Alina A. Vitrishchak1, Boris I. Smirnov2, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1

1 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia
2 Saint Petersburg State Electrotechnical University, St. Petersburg, Russia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective treatment in high risk hematological malignancies. Nevertheless, the relapse rates after allo-HSCT range from 10% to 70%.There is no optimal strategy of the relapse therapy after allo-HSCT. Possible therapeutic options include re-induction chemotherapy, immunoadoptive therapy (DLI), target drugs, immunotherapy (CAR-T) and second allo-HSCT. The presented study is a retrospective single-institution experience of second allo-HSCT in the patients (pts) with acute leukemia relapses or graft failure in high-risk cases. The aim of our study was to analyze the outcomes after second allo-HSCT in 50 children with hematological malignancies, i.e., ALL (n=24), AML (n=15), MPDs/MDS (n=11).

Results

Forty-four patients achieved engraftment, with median neutrophil engraftment time of 21 days (12 to 41). Remission was achieved in 44 pts (88%). Median follow-up period was 3 years 7 months. Overall survival (OS), according to Kaplan-Meier method, was 48% in the whole group. Relapse-free survival (RFS) was 60%. The five-year OS in ALL group was 46.2%; in AML group, 53.3%; in MPDs/MDS, 44.4%. Causes of death were as follows: relapse/progression in 65% (n=17), transplant-related mortality (TRM), in 18% (n=9; 95%CI, 8.8%-29.8%); cumulative relapse rate was 34% (95% CI, 21.6%-48%).

Conclusion

Second allo-HSCT is an effective treatment option in cases of relapse after 1st allo-HSCT. The patients that achieved remission or even blast cytoreduction prior to 2nd allo-HSCT had better outcome. Clinical manifestations of acute and chronic GVHD can significantly improve the OS. Results of 2nd allo-HSCT were comparable when using RIC or MAC conditioning regimens. Posttransplant therapy is required to improve results after 2nd HSCT.

Keywords

Leukemia relapse, second allogeneic HSCT, posttransplant therapy, children.

Clinical studies

Intrathecal enzyme replacement therapy for CLN2 disease

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Alfried Kohlschütter

University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Neuronal сeroid-lipofuscinosis 2 (CLN2) is a genetic, rapidly progressive brain disorder of young humans. It leads to dementia, dramatic loss of all abilities and early death. It is caused by the deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) in the nervous system. This article is an overview of the development of replacing the deficient enzyme by repeated infusion of recombinant TPP1 in a brain ventricle, shown to be effective in halting the rapid progression of the disease.

Keywords

Neuronal сeroid-lipofuscinosis 2, tripeptidyl peptidase 1, deficiency, dementia, recombinant enzyme, local infusion, clinical effect.

Clinical studies

Common bacterial cultures from oral mucosa after hematopoietic stem cell transplantation: dependence on the patient characteristics and therapeutic factors

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Alexei B. Chukhlovin1, Anna A. Spiridonova2, Irina B. Baranova3, Artur P. Grigoriants3, Maria D. Vladovskaya1, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1

1 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, St. Petersburg, Russia
2 Department of Clinical Microbiology, Pavlov University, St. Petersburg, Russia
3 Department of Orofacial Surgery, Pavlov University, St. Petersburg, Russia

Normal aerobic and facultative anaerobic microbiota colonizing oral mucosa is usually identified at clinical laboratories. Its composition may be important index of immunocompromised conditions. These parameters are scarcely studied in patients undergoing hematopoietic stem cell transplantation (HSCT). The aim of this work was to evaluate incidence of common aerobic and facultative anaerobic microbiota cultured from oral samples taken before HSCT and, by clinical indications, within 4 months after the treatment.

Patients and methods

We evaluated results of bacterial cultures from oral smears taken in 202 patients with oncohematological and inborn diseases at the age ranging from 1 to 69 years subjected to allogeneic HSCT. The analysis was performed for 3 age groups: 1-5, 6-14, 15-21, and >22 years old.

Results

In total observation group of 630 oral samples, the bacterial cultures proved to be positive in 61.8% of specimens. The most common microorganisms were as follows: S.viridans 245/630 (38.9%); K.pneumoniae 42/630 (6.7%); S.epidermidis 120/630 (19.1%); Neisseria spp. 66/630 (10.5%); Corynebacterium spp. 78/630 (12.4%). The incidence of microbial detection was time-dependent, with significant decrease in S.epidermidis, Corynebacterium spp. and Klebsiella spp. during 1st month posttransplant which could be explained by early effective antibacterial decontamination since the time of conditioning in early posttransplant period. We have shown that the frequency of positive tests for S.viridans and K.pneumoniae in these samples were different for distinct age groups, i.e., the positivity rates were significantly higher in youngest children (up to 5 years old) and in adult patients (>22 years old), as compared with elder children and adolesсents. Incidence of K.pneumoniae in oral samples was found to be sufficiently increased 2-3 months after HSCT, being associated with severe infectious complications, with broad antibiotic resistance in most culturable Klebsiella isolates from the patients. For clinical indications, teeth extraction was made in 10 cases during 1st month after HSCT, with Pseudomonas aeruginosa in 3 samples, S.viridans in 2 cases isolated from the local gum wounds. In conclusion, the immunotoxic effects of cytostatic therapy and microbiota analysis post-HSCT deserve further studies, including biodiversity analysis of oral microbiota by means of 16S rRNA gene sequencing. These results may represent a basis for rational antibacterial therapy in HSCT.

Keywords

Oncohematology, children, chemotherapy, hematopoietic stem cell transplantation, bacterial cultures, risk factors.

Clinical case

Haemorrhagic enteritis associated with parvovirus B19 following hematopoietic stem cell transplantation: a case report and literature data

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Oleg V. Goloshchapov1, Natalia D. Ventslovayte1, Ruslana V. Klementeva1, Alexander N. Shvetsov1, Aleksandr A. Shcherbakov1, Maria O. Goloshchapova1, Vadim E. Karev2, Boris V. Afanasyev1

1 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia
2 Federal Pediatric Research Center of Infectious Diseases, St. Petersburg, Russia

Parvovirus (PV) B19 infection is rather spread worldwide and manifests with a range of clinical symptoms. The aim of our report was to demonstrate a rare case of haemorrhagic enteritis associated with parvovirus B19 in the patient after allogeneic hematopoietic stem cell transplantation (allo-HSCT).We present here a clinical case of PV infection which proceeded as acute haemorrhagic enteritis in 52-year male patient who underwent HSCT. Distinct expression of antigens specific for PV B19 was revealed on autopsy by means of immunohistochemical testing, along with PVB19 DNA found in stomach, small intestine tissues and myocardial samples by means of PCR technique.

Keywords

Parvovirus B19, allogeneic hematopoietic stem cell transplantation, clinical infection, haemorrhagic enteritis, myocarditis, intestinal bleeding.

Rehabilitation

Effects of motor exercises upon life quality of adolescents subjected to hematopoietic stem cell transplantation

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Alla A. Potapchuk1, Alisa G. Volkova1, Fedor V. Terentiev2, Irina G. Terentieva2, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1

1 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University,
St. Petersburg, Russia
2 National State P. F. Lesgaft University of Physical Culture, Sports and Health, St. Petersburg, Russia

The present article is evaluating the effects of physical rehabilitation upon the quality of life (QoL) indexes in adolescents (12 to 17 y.o.) with oncological diseases following hematopoietic stem cell transplantation (HSCT). The proprietary technique of physical rehabilitation includes 3 stages with nine complexes of physical exercises, dependent on their age and regimen of motor activities. We have evaluated QoL, and anxiety/depressive conditions in adolescents at three stages of the study: HSCT, after it, and following rehabilitation. The data obtained confirm a positive effect of the physical rehabilitation upon QoL in the adolescents with cancer subjected to hematopoietic stem cell transplantation.

Keywords

Physical rehabilitation, oncology, children, hematopoietic stem cell transplantation, depression, anxiety, emotional state.

Rehabilitation

Sensory conflict as a possible reason for disturbed postural stability in the children treated for cancer

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Serafima M. Chechelnitskaia, Vladimir N. Kasatkin, Marina A. Shurupova, Irina D. Borodina, Yurij V. Sarajkin, Aleksandr F. Karelin, Dmitrij V. Skvorcov, Aleksandra V. Baerbakh, Daria V. Zhuk, Vladislav A. Nikulin

Medical Rehabilitation Research Center "Russkoe Pole", Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

Disorders of postural resistance are widespread among the patients treated for cancer. The question of the mechanism of this phenomenon is under the study. The aim of our retrospective study was to clarify the relationship of postural instability in cancer patients with oculomotor muscle dysfunction.

Patients and methods

The study involved 291 children 5-18 years old who had cancer and were in remission state or stable clinical condition. The control group included 182 healthy children. The quality of postural balance was evaluated by stabilometric method using a computer-assisted stabilizer (Stabilan 01-2 model). The eye movements were recorded by videoculography using the Arrington eye-tracker. Regression analysis was used to assess relationships of the analyzed parameters. For explicit asymmetric distributions, we used conversion of initial values to logarithmic form and the Box-Cox transformation.

Results

The main stabilometric indicators in the position with open eyes confirmed impaired postural balance in the children who survived cancer. We have substantiated a high probability of correlation between the postural imbalance and disease factor. Improvement in stabilometric indexes with eyes closed was detected for both groups. However, this phenomenon proved to be significant and was more common among the children who survived cancer.

Conclusion

A stable relationship was found between the postural instability and altered functioning of oculomotor muscles.

Keywords

Childhood cancer, postural control, anticancer therapy, toxic effects, oculomotor muscles.

Experimental studies

Game of genomes: to be continued

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Kristina A. Zakurdaeva

Foundation for Cancer Research Support (RakFond), Moscow, Russia

The landscape of genome editing has dramatically changed over the recent five years, and evolved from scientific ideas and laboratory research to multiple clinical applications changing patients’ lives, creating new commercial opportunities with substantial investments in the field and notable deals, and societal dilemmas raising many discussion items for the medical community and general public. Today, many of the cutting-edge R&D efforts, investments, regulatory initiatives, and ethical discussions occur in this field. In what way can the market and society keep up with the latest scientific discoveries, and what is the next big thing to come?

In this essay, I will discuss the opportunities and challenges of current cell and gene therapy market, recent approvals and their clinical and economic impact, novel technologies that are entering clinical trials, and ethical considerations that some of these technologies and/or their applications provoke.

Keywords

Genome editing, investments, market, research & development, ethics.

Experimental studies

Adipose-derived mesenchymal stem cells (ASCs) transplantation restored olfactory function in anosmic rats

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Bijan Khademi1,2, Zohreh Zandifar2, Ahmad Monabati3, Nooshafarin Chenari4, Abbas Ghaderi4,5, Mahboobeh Razmkhah4

1 Research Center of Otolaryngology Head and Neck Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Otorhinolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Olfactory dysfunction is a major challenge in medicine and there is no absolute treatment for anosmic patients. Adipose-derived mesenchymal stem cells (ASCs) are multipotent cells capable of differentiating into several cell lineages. The aim of present study was to assess effects of ASCs upon restoration of the olfactory function in anosmic rats.

Materials and methods

ASCs were isolated from the periuterine fat tissue of rats using collagenase type I. Anosmia was induced by intraperitoneal injection of 3-methylindole. Further on, 5×105 ASCs were transnasally transferred into the case group one day after the induction of anosmia. The control group included anosmic rats that were injected with culture media without ASCs. The olfactory function was evaluated weekly by a food-finding test. Olfactory neuroepithelium and bulb were harvested for histopathologic study at 4 and 8 weeks.

Results

Injection of ASCs caused about seven- and six-fold statistically significant reduction in the food-finding time in the case group of rats when compared to the control group tested, respectively, 4 and 8 weeks after injection of ASCs (P-value= 0.00 and =0.035, respectively). Histopathological findings showed reconstruction of olfactory neuroepithelium in 93% of the cases while it was detected in 50% of control rats. The olfactory bulb was detectable in 60% of the case group rats, compared with 20% of the control rats.

Conclusion

Our present results show that regeneration of olfactory epithelium may be accelerated using local ASCs treatment. These data suggest that ASCs might be a promising source for the treatment of olfactory dysfunction in the future.

Keywords

Anosmia, experimental, mesenchymal stem cells, adipose-derived, differentiation, neural cells.

Experimental studies

Experimental study of polymer-based scaffolds promoting bone tissue repair in oroantral communication

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Аndrey I. Yaremenko1, Anna V. Lysenko1, Elizaveta A. Ivanova1, Galina U. Ukina4, Alexander D. Vilesov3, Marina A. Chibisova5, Anna A. Zubareva2, Оleg V. Galibin3

1 Department of Maxillofacial Surgery, Pavlov University, St. Petersburg, Russia
2 Department of Otorhinolaryngology, Pavlov University, St. Petersburg, Russia
3 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, St. Petersburg, Russia
4 Research Center, Pavlov University, St. Petersburg, Russia
5 Saint Petersburg Stomatology Institute of Postgraduate Education, St. Petersburg, Russia

Odontogenic maxillary sinusitis (OMS) takes one of the leading position among the paranasal sinus diseases. According to current reviews, the number of patients with OMS is increasing every year, and makes up from 4 to 7% of the maxillofacial diseases. Recently, a perforating form of OMS becomes more common in practice of maxillofacial surgery. Perforative sinusitis occurs due to break of mucoperiosteum in response to some pathological conditions, most frequently, following extraction of a superior tooth. Therefore, improvement of existing approaches and development of new affordable and less traumatic methods for treatment of sinusitis remains quite relevant. Over last years, usage of polymer materials (both natural and artificial products) has become increasingly popular in maxillofacial and dental surgery. Such materials should have several favorable properties: lack of cytotoxicity, biocompatibility, resorbability and good handling characteristics. The synthetic polymer polycaprolactone (PCL) meets these requirements to a greater extent. Due to its three-dimensional porous structure, these polymers are actively used in tissue engineering. Available data on the opportunity of bone tissue regeneration by the polymer structures suggest that they can be used to stimulate osteogenesis and maintain the height of the alveolar process of the upper jaw in cases of oroantral communication (OAC) occurring after tooth extraction. Of note, PCL is a safe material approved by the FDA for use in drug delivery devices and implantation scaffolds. Considering these data, it is of great interest to evaluate the opportunity of its application in the sites of inflammation, e.c., for elimination of OAC defect in presence of developing sinusitis. The aim of our study was to evaluate the opportunity of using a PCL matrix in order to close the OAC using an in vivo experimental model.

Materials and methods

In an experimental study, xenogeneic transplantation of polycaprolactone matrix was performed into the lower wall of maxillary sinus after the OAC development in rabbits. Nine animals were sacrificed after 4, 8 and 24 weeks. The maxillary bones were dissected, cut into smaller blocks, and the specimens were immediately placed in formalin. Serial sections were stained and examined using light microscope.

Results

The morphological study showed that there are early signs of connective tissue ingrowth to the matrix mesh 1 month after implantation. The surrounding capsule was thin and showed minimal signs of inflammation, which completely disappeared by the second month after the intervention. Over the next 4 months, the capsule becomes thinner, the matrix was totally penetrated by connective tissue and blood vessels. It helped to retain the height of alveolar process in the upper jaw at the site of tooth extraction. In conclusion, the proposed method for OAC closure by means of the PCL scaffold system can retain the space of the lost maxillary bone fragment for up to 6 months being able to stimulate osteogenesis, as shown by our animal experiments.

Keywords

Oroantral communication, maxillary sinus, polycaprolactone, polymer scaffolds, bone regeneration.

Supplement 1

Indications for hematopoietic stem cell transplantation

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Editor: Prof. Dr. Boris V. Afanasyev

Ksenia S. Afanasyeva, Maria V. Barabanshchikova, Sergey N. Bondarenko, Tatyana A. Bykova, Julia Yu. Vlasova, Asmik G. Gevorgian, Irina K. Golubovskaya, Elena I. Darskaya, Yury R. Zalyalov, Darya A. Zvyagintseva, Ludmila S. Zubarovskaya, Maria O. Ivanova, Ilya V. Kazantsev, Olga B. Kalashnikova, Andrey V. Kozlov, Elena V. Kondakova, Vladislav O. Korolenko, Olga V. Kudyasheva, Alexander D. Kulagin, Elena E. Lepik, Kirill V. Lepik, Inna V. Markova, Irina A. Mikhailova, Natalya B. Mikhailova, Ivan S. Moiseev, Elena V. Morozova, Anna A. Osipova, Olesya V. Paina, Olga V. Pirogova, Alexey Yu. Polushin, Marina O. Popova, Valentina V. Porunova, Yury A. Punanov, Elena V. Semenova, Anna G. Smirnova, Olesya V. Smykova, Polina S. Tolkunova, Lyudmila V. Fedorova, Nikolay Yu. Tcvetkov, Ivan V. Tsygankov, Tatyana V. Yukhta

Dear colleagues,
We are glad to welcome you again at the XIII R. Gorbacheva Memorial Symposium Hematopoietic Stem Cell Transplantation. Gene and Cellular Therapy in Saint Petersburg.

Our annual forum invites specialists who are focused on scientific and practical issues of hematopoietic stem cell transplantation (HSCT). The lectures presented by leading experts, quite recent data in the field of clinical studies, discussions and sharing experience in this area allow to extend knowledge and to increase professional level of the specialists participating at the Symposium.

Intending for better information in the field and pursuing educational aims, we are bringing to your notice the second edition of our booklet Indications for Hematopoietic Stem Cell Transplantation which contains the main indications for HSCT, brought into compliance with updated guidelines from European Society for Blood and Marrow Transplantation (EBMT) published in the official journal Bone Marrow Transplantation (published April 5, 2019): Duarte RF, Labopin M, Bader P, Basak GW, Bonini C, Chabannon C, Corbacioglu S, Dreger P, Dufour C, Gennery AR, Kuball J, Lankester AC, Lanza F, Montoto S, Nagler A, Peffault de Latour R, Snowden JA, Styczynski J, Yakoub-Agha I, Kröger N, Mohty M; for the European Society for Blood and Marrow Transplantation (EBMT). Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. (2019). 10.1038/s41409-019-0516-2.

We express a hope that this publication will be manageable and user-friendly to Russian-speaking readers.

Professor Boris V. AFANASYEV
Pavlov University, St. Petersburg, Russia