array(4) { [0]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "34" ["~IBLOCK_SECTION_ID"]=> string(2) "34" ["ID"]=> string(3) "852" ["~ID"]=> string(3) "852" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["~NAME"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "06/14/2017 01:59:14 pm" ["~TIMESTAMP_X"]=> string(22) "06/14/2017 01:59:14 pm" ["DETAIL_PAGE_URL"]=> string(128) "/en/archive/Volume-1/stati/opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli/" ["~DETAIL_PAGE_URL"]=> string(128) "/en/archive/Volume-1/stati/opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(15807) "

Introduction

Myeloproliferative disorders (MPDs) comprise a group of hematopoietic malignancies that are characterized by enhanced proliferation and survival of one or more myeloid line cells [1]. According to the World Health Organization classification, MPDs include polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IMF) and chronic myeloid leukemia (CML), plus rarer subtypes, such as chronic neutrophilic leukemia, hypereosinophilic syndrome and chronic eosinophilic leukemia [8]. The clinical picture of these disorders has many features: all malignant cells originate from a single, multipotent hematopoietic stem cell that predominates over nontransformed progenitors; hypercellularity of the bone marrow, with apparently unstimulated overproduction of one or more of the blood corpuscles; and increased risk of thrombosis and bleeding, spontaneous transformation into acute leukemia and marrow fibrosis [3]. Until very recently MPDs continued to be separated and diagnosed on the basis of their clinical and laboratory findings [4]. The identification of new genetic markers represents a major advance in the understanding of the molecular pathogenesis of MPDs, which will likely result in new classifications and the development of novel therapeutic strategies for these diseases.

The most extensively studied mutation is BCR/ABL, the pathogenetic mutation in CML [5]. CML was the first leukemia to be described and associated with a consistent cytogenetic abnormality, the Philadelphia chromosome (Ph1). Since then new approaches, based on detection of different mutations, have been effectively developed.

The discovery of the JAK2V617F mutation has already greatly influenced the diagnostic approach for MPDs, as well as research strategies in terms of both molecular pathogenesis and drug development [6].

JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, could be found in nearly all patients with polycythemia vera (PV), in approximately 50% in both essential thrombocythemia (ET) and myelofibrosis (MF) patients, up to 20% of the time in certain subcategories of atypical MPD, in less than 3% in de novo MDS or acute myeloid leukemia patients, and 0% of cases of CML [7].

The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway plays a central role in initiating signal transduction from hematopoietic growth factor receptors. Non-receptor tyrosine kinases JAK2 are normally responsible for signaling from various growth factor receptors, including those for erythropoietin and thrombopoietin. Each JAK protein has two active tyrosine kinase domains and a catalytically inactive pseudokinase domain. Under normal physiological circumstances, the pseudokinase domain prevents the closure of the two tyrosine kinase domains and auto-activation. When a ligand (for example erythropoietin) binds with a receptor, a conformational change occurs. The JAK2 protein then contacts the cytoplasmic domain of the receptor, where it catalyses tyrosine phosphorylation. This primarily leads to the recruitment of STAT (signal transducer and activator of transcription) molecules, which are then phosphorylated, homodimerize and translocate to the nucleus, where they act as transcription factors [8]. These processes are key events in the modification of regulatory pathways for cell proliferation and survival.

The specific genetic mutation G1849T observed in exon 14 results in the substitution of phenylalanine by valine, both hydrophobic nonpolar amino acids, at position 617 of the JAK2 protein within the JH2 pseudokinase domain [9]. Loss of JAK2 auto-inhibition results in constitutive activation of the kinase. It results in deregulation of intracellular signaling and disturbance of cell proliferation, which becomes independent of normal growth factor control. Since the mutation has a high specificity for clonal myeloid diseases, the presence of JAK2 V617F can definitively confirm an MPD diagnosis [10].

The main aim of this study was to develop a routine detection technique for the V617F mutation of the JAK2 gene that will be useful both for primary diagnostics and for semiquantative estimation during treatment.

Patients, materials, and methods

Patient characteristics
Fifty-eight patients from hematological clinics of the Saint Petersburg Pavlov State Medical University were included in the study: 8 patients with PV, 7 with ET, 2 with MF and 35 with primary diagnosed MPD. The median age was 55 years (range 20–86 years). All patients did not receive any specific therapy. The control group included 20 standard blood donors.

Cell line
As a positive control we used cell line UKE1 [11], donated by Professor B. Fehse (Germany). The UKE1 cell line is homozygous for the V617F mutation in the Jak2 gene (G1849T substitution in exon 14) [12].

DNA samples
DNA was isolated from 200 µl of bone marrow or 1 ml whole blood using sorbate methods (DNA Technology, Russia). This procedure regularly results in 3 µg to 8 µg DNA in a final volume of 100 µl. After isolation from blood samples, DNA was stored at -20 °C until analysis.

PCR analysis
PCR was performed on an amplificator “Terzik” (DNA Technology, Russia) with standard PCR mix. The program for PCR includes initial denaturation (3 minutes at 95°C) and 40 cycles at 94°C for 20 seconds; 61°C for 30 seconds and 72°C for 60 seconds. The following primers were used: Jak2-F (forward): 5'-GGGTTTCCTCAGAACGTTGA-3'; Jak2-RW (reverse wild type): 5'-TTTACTTACTCTCGTCTCCACATAC-3'; Jak2-RM (reverse mutated): 5'-TTTACTTACTCTCGTCTCCACATAA-3'. After amplification PCR products were visualized in 2% agarose gel and photographed by means of a "Gel Imager, 08-111" (DNA Technology, Russia).
Real-time PCR was performed on a DT-96 amplificator (DNA Technology, Russia), with standard PCR real time mix SYBR GREEN and the same primers. After initial denaturation (3 minutes at 95°C), PCR was carried out for 40 cycles at standard conditions (94°C for 15 seconds; 61°C for 40 seconds). The estimation of "threshold" was performed automatically; "melting curve" analysis was used for discrimination of the nonspecific results.

Results assessment
To assess the specificity of the method we used the UKE1 cell line and 20 donor samples as negative control.

A)    Quality assessment

Each sample was assessed on two lines: line 1 – PCR specific for the wild- type of the Jak2 gene, and line 2 – specific for the mutated gene. If the mutation-specific signal in line 2 was detected, such samples were considered positive for the V617F mutation in the Jak2 gene (see Figure 1).

B) Semi quantitative assessment

A semi-quantitative assessment was performed by means of the GelPro Analyzer 3.1 computer program. This program allows the quantitative valuation of luminescence levels and assesses those in Relative Units of Luminescence (RU). The sum of RU from two lines (wild and mutated type of gene) was assessed as 100%. Relative intensity of mutant type gene signals thus indicates the number of mutated cells.

Results and discussion

Screening for the JAK2V617F mutation in MPD diagnostics is a predictive and specific approach [13]. In most cases the JAK2 V617F mutation was examined using polymerase chain reaction (PCR)-amplified genomic DNA with two primers (for mutant and wild type gene) [12]. Concerning the results of this study such a method is appropriate for screening the mutation.

As a positive control we used cell line UKE1, which is homozygous for the V617F JAK2 mutation. For negative control we used samples from 20 healthy donors who do not carry this mutation after informed consent. The correlation analysis showed high-level convergence between real time and standard PCR dates. “Melting curve” analysis showed high level specificity and sensitivity.

Prospective evaluation of the V617F JAK2 mutation was implemented at Saint Petersburg Pavlov State Medical University. Fifty-eight patients with a preliminary diagnosis of MPD were examined. The overall mutation frequency was 29.3%. The incidence of different diseases is shown in Table 1.

Table 1. Overall frequency of the V617F JAK2 mutation in 58 patients with different myeloproliferative disorders at the Saint Petersburg Pavlov State Medical University.

Detection of V617F mutation of JAK2 gene in patients with chronic myeloproliferative disorders is a common criterion for diagnosis. For primary diagnostics, screening methods are widely used. Such methods should be quick in performance, rather cheap and reproducible in laboratories with technical equipment of middle level.

For screening methods, qualitative detection of the JAK2 gene mutation without its quantitative assessment is sufficient. Detection of this mutation helps not only in diagnostics, but also in determining the treatment strategy for a concrete patient.

After specific therapy (standard chemotherapy and particularly hematopoietic stem cells transplantation) it is rather important to assess dynamics of reduction of the tumor clone that bears the mutation in the JAK2 gene. Another substantial goal is to follow minimal amounts of tumor cells (“minimal residual disease”) to predict potential recurrence of the disease. For this purpose both semiquantitative and quantitative methods are appropriate. Quantitative methods need verified controls (e.g. cell line or plasmid dilutions) for establishing a calibration curve.

Concerning the abovementioned protocol we have developed a screening method for the detection of the V617F mutation in the JAK2 gene. This method is based on common allele-specific amplification with further detection in agarose gel. Specificity and sensitivity of this method were tested on the cell line UКE1 (data are not presented). Using this protocol we retrospectively investigated 23 patients with clinically verified diagnoses (see Table 1), and performed prospective trial on 35 outpatients with suspected myeloproliferative disorders.

Comparing our results with data from literature we indicated similarity of incidence rates for V617F mutation in JAK2 gene in patients with idiopathic myelofibrosis and essential thrombocythemia. Discrepancy between incidence rates in patients with polycythemia vera and unspecified myeloproliferative disorders and data from literature could be referred to small sample and/or and shortage of clinical criteria for diagnosis verification. Besides specificity we assessed reproducibility of this method on different types of amplificators – «GeneAmp»-9600 (USA), DT-96 (Russia), «Tercic» (Russia). We showed identity of data obtained on different amplificators, which confirms high reproducibility of the proposed method. All samples positive for V617F mutation in JAK2 gene were analyzed with computer program “GelPrо” to determine percentage ratio of tumor and normal cells.

At the second phase of our study we developed a uniform qualitative method for detection of the JAK2V617F mutation using real-time PCR. Therefore we used the same samples as for the standard PCR analysis. Preliminary data of qPCR analysis were in full agreement with those of standard PCR (not shown). Further refinement may be carried out in order to develop a simple quantitative method to assess minimal residual disease after standard treatment and transplantation.

In conclusion the proposed PCR method for the detection of the JAK2 mutation seems to be suitable for the initial evaluation of patients with myeloproliferative disorders.

References

1. Steensma DP. JAK2 V617F in Myeloid Disorders: Molecular Diagnostic Techniques and Their Clinical Utility. JMD. 2006;8(4):397-410.

2. Tefferi А, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22:14-22.

3. Yamaoka K, Saharinen P, Pesu M, Holt VE 3rd, Silvennoinen O, O’Shea JJ. The Janus kinases (Jaks). Genome Biology. 2004;5:253.

4. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6:372-375.

5. Wilson-Rawls J, Xie S, Liu J, Laneuville P, Arlinghaus RB. P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation. Cancer Res. 1996;56:3426-3430.

6. Spivak JL, Barosi G, Tognoni G, Barbui T, Finazzi G, Marchioli R, Marchetti M. Chronic myeloproliferative disorders. Hematology: American Society of Hematology Education Program Book. 2003:200-224.

7. McLornan D, Percy M, McMullin MF. JAK2 V617F: A Single Mutation in the Myeloproliferative Group of Disorders. Ulster Med J. 2006;75(2):112-119.

8. Tefferi А. Classification, Diagnosis and Management of Myeloproliferative Disorders in the JAK2V617F Era. Hematology. 2006;240-245.

9. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2V617F mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131(2):208-13.

10. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247:824-830.

11. Fiedler W, Henke RP, Ergün S, Schumacher U, Gehling UM, Vohwinkel G, Kilic N, Hossfeld DK. Derivation of a new hematopoietic cell line with endothelial features from a patient with transformed myeloproliferative syndrome: a case report. Cancer. 2000 Jan 15;88(2):344-51.

12. Lippert E, Girodon F, Hammond E, et al. Concordance of assays designed for the quantification of JAK2V617F: a multicenter study. Haematologica. 2008 Nov 10. Epub ahead of print.

13. Levine RL, Wernig G. Role of JAK-STAT Signaling in the Pathogenesis of Myeloproliferative Disorders. Hematology. 2006:233-239.

" ["~DETAIL_TEXT"]=> string(15807) "

Introduction

Myeloproliferative disorders (MPDs) comprise a group of hematopoietic malignancies that are characterized by enhanced proliferation and survival of one or more myeloid line cells [1]. According to the World Health Organization classification, MPDs include polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IMF) and chronic myeloid leukemia (CML), plus rarer subtypes, such as chronic neutrophilic leukemia, hypereosinophilic syndrome and chronic eosinophilic leukemia [8]. The clinical picture of these disorders has many features: all malignant cells originate from a single, multipotent hematopoietic stem cell that predominates over nontransformed progenitors; hypercellularity of the bone marrow, with apparently unstimulated overproduction of one or more of the blood corpuscles; and increased risk of thrombosis and bleeding, spontaneous transformation into acute leukemia and marrow fibrosis [3]. Until very recently MPDs continued to be separated and diagnosed on the basis of their clinical and laboratory findings [4]. The identification of new genetic markers represents a major advance in the understanding of the molecular pathogenesis of MPDs, which will likely result in new classifications and the development of novel therapeutic strategies for these diseases.

The most extensively studied mutation is BCR/ABL, the pathogenetic mutation in CML [5]. CML was the first leukemia to be described and associated with a consistent cytogenetic abnormality, the Philadelphia chromosome (Ph1). Since then new approaches, based on detection of different mutations, have been effectively developed.

The discovery of the JAK2V617F mutation has already greatly influenced the diagnostic approach for MPDs, as well as research strategies in terms of both molecular pathogenesis and drug development [6].

JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, could be found in nearly all patients with polycythemia vera (PV), in approximately 50% in both essential thrombocythemia (ET) and myelofibrosis (MF) patients, up to 20% of the time in certain subcategories of atypical MPD, in less than 3% in de novo MDS or acute myeloid leukemia patients, and 0% of cases of CML [7].

The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway plays a central role in initiating signal transduction from hematopoietic growth factor receptors. Non-receptor tyrosine kinases JAK2 are normally responsible for signaling from various growth factor receptors, including those for erythropoietin and thrombopoietin. Each JAK protein has two active tyrosine kinase domains and a catalytically inactive pseudokinase domain. Under normal physiological circumstances, the pseudokinase domain prevents the closure of the two tyrosine kinase domains and auto-activation. When a ligand (for example erythropoietin) binds with a receptor, a conformational change occurs. The JAK2 protein then contacts the cytoplasmic domain of the receptor, where it catalyses tyrosine phosphorylation. This primarily leads to the recruitment of STAT (signal transducer and activator of transcription) molecules, which are then phosphorylated, homodimerize and translocate to the nucleus, where they act as transcription factors [8]. These processes are key events in the modification of regulatory pathways for cell proliferation and survival.

The specific genetic mutation G1849T observed in exon 14 results in the substitution of phenylalanine by valine, both hydrophobic nonpolar amino acids, at position 617 of the JAK2 protein within the JH2 pseudokinase domain [9]. Loss of JAK2 auto-inhibition results in constitutive activation of the kinase. It results in deregulation of intracellular signaling and disturbance of cell proliferation, which becomes independent of normal growth factor control. Since the mutation has a high specificity for clonal myeloid diseases, the presence of JAK2 V617F can definitively confirm an MPD diagnosis [10].

The main aim of this study was to develop a routine detection technique for the V617F mutation of the JAK2 gene that will be useful both for primary diagnostics and for semiquantative estimation during treatment.

Patients, materials, and methods

Patient characteristics
Fifty-eight patients from hematological clinics of the Saint Petersburg Pavlov State Medical University were included in the study: 8 patients with PV, 7 with ET, 2 with MF and 35 with primary diagnosed MPD. The median age was 55 years (range 20–86 years). All patients did not receive any specific therapy. The control group included 20 standard blood donors.

Cell line
As a positive control we used cell line UKE1 [11], donated by Professor B. Fehse (Germany). The UKE1 cell line is homozygous for the V617F mutation in the Jak2 gene (G1849T substitution in exon 14) [12].

DNA samples
DNA was isolated from 200 µl of bone marrow or 1 ml whole blood using sorbate methods (DNA Technology, Russia). This procedure regularly results in 3 µg to 8 µg DNA in a final volume of 100 µl. After isolation from blood samples, DNA was stored at -20 °C until analysis.

PCR analysis
PCR was performed on an amplificator “Terzik” (DNA Technology, Russia) with standard PCR mix. The program for PCR includes initial denaturation (3 minutes at 95°C) and 40 cycles at 94°C for 20 seconds; 61°C for 30 seconds and 72°C for 60 seconds. The following primers were used: Jak2-F (forward): 5'-GGGTTTCCTCAGAACGTTGA-3'; Jak2-RW (reverse wild type): 5'-TTTACTTACTCTCGTCTCCACATAC-3'; Jak2-RM (reverse mutated): 5'-TTTACTTACTCTCGTCTCCACATAA-3'. After amplification PCR products were visualized in 2% agarose gel and photographed by means of a "Gel Imager, 08-111" (DNA Technology, Russia).
Real-time PCR was performed on a DT-96 amplificator (DNA Technology, Russia), with standard PCR real time mix SYBR GREEN and the same primers. After initial denaturation (3 minutes at 95°C), PCR was carried out for 40 cycles at standard conditions (94°C for 15 seconds; 61°C for 40 seconds). The estimation of "threshold" was performed automatically; "melting curve" analysis was used for discrimination of the nonspecific results.

Results assessment
To assess the specificity of the method we used the UKE1 cell line and 20 donor samples as negative control.

A)    Quality assessment

Each sample was assessed on two lines: line 1 – PCR specific for the wild- type of the Jak2 gene, and line 2 – specific for the mutated gene. If the mutation-specific signal in line 2 was detected, such samples were considered positive for the V617F mutation in the Jak2 gene (see Figure 1).

B) Semi quantitative assessment

A semi-quantitative assessment was performed by means of the GelPro Analyzer 3.1 computer program. This program allows the quantitative valuation of luminescence levels and assesses those in Relative Units of Luminescence (RU). The sum of RU from two lines (wild and mutated type of gene) was assessed as 100%. Relative intensity of mutant type gene signals thus indicates the number of mutated cells.

Results and discussion

Screening for the JAK2V617F mutation in MPD diagnostics is a predictive and specific approach [13]. In most cases the JAK2 V617F mutation was examined using polymerase chain reaction (PCR)-amplified genomic DNA with two primers (for mutant and wild type gene) [12]. Concerning the results of this study such a method is appropriate for screening the mutation.

As a positive control we used cell line UKE1, which is homozygous for the V617F JAK2 mutation. For negative control we used samples from 20 healthy donors who do not carry this mutation after informed consent. The correlation analysis showed high-level convergence between real time and standard PCR dates. “Melting curve” analysis showed high level specificity and sensitivity.

Prospective evaluation of the V617F JAK2 mutation was implemented at Saint Petersburg Pavlov State Medical University. Fifty-eight patients with a preliminary diagnosis of MPD were examined. The overall mutation frequency was 29.3%. The incidence of different diseases is shown in Table 1.

Table 1. Overall frequency of the V617F JAK2 mutation in 58 patients with different myeloproliferative disorders at the Saint Petersburg Pavlov State Medical University.

Detection of V617F mutation of JAK2 gene in patients with chronic myeloproliferative disorders is a common criterion for diagnosis. For primary diagnostics, screening methods are widely used. Such methods should be quick in performance, rather cheap and reproducible in laboratories with technical equipment of middle level.

For screening methods, qualitative detection of the JAK2 gene mutation without its quantitative assessment is sufficient. Detection of this mutation helps not only in diagnostics, but also in determining the treatment strategy for a concrete patient.

After specific therapy (standard chemotherapy and particularly hematopoietic stem cells transplantation) it is rather important to assess dynamics of reduction of the tumor clone that bears the mutation in the JAK2 gene. Another substantial goal is to follow minimal amounts of tumor cells (“minimal residual disease”) to predict potential recurrence of the disease. For this purpose both semiquantitative and quantitative methods are appropriate. Quantitative methods need verified controls (e.g. cell line or plasmid dilutions) for establishing a calibration curve.

Concerning the abovementioned protocol we have developed a screening method for the detection of the V617F mutation in the JAK2 gene. This method is based on common allele-specific amplification with further detection in agarose gel. Specificity and sensitivity of this method were tested on the cell line UКE1 (data are not presented). Using this protocol we retrospectively investigated 23 patients with clinically verified diagnoses (see Table 1), and performed prospective trial on 35 outpatients with suspected myeloproliferative disorders.

Comparing our results with data from literature we indicated similarity of incidence rates for V617F mutation in JAK2 gene in patients with idiopathic myelofibrosis and essential thrombocythemia. Discrepancy between incidence rates in patients with polycythemia vera and unspecified myeloproliferative disorders and data from literature could be referred to small sample and/or and shortage of clinical criteria for diagnosis verification. Besides specificity we assessed reproducibility of this method on different types of amplificators – «GeneAmp»-9600 (USA), DT-96 (Russia), «Tercic» (Russia). We showed identity of data obtained on different amplificators, which confirms high reproducibility of the proposed method. All samples positive for V617F mutation in JAK2 gene were analyzed with computer program “GelPrо” to determine percentage ratio of tumor and normal cells.

At the second phase of our study we developed a uniform qualitative method for detection of the JAK2V617F mutation using real-time PCR. Therefore we used the same samples as for the standard PCR analysis. Preliminary data of qPCR analysis were in full agreement with those of standard PCR (not shown). Further refinement may be carried out in order to develop a simple quantitative method to assess minimal residual disease after standard treatment and transplantation.

In conclusion the proposed PCR method for the detection of the JAK2 mutation seems to be suitable for the initial evaluation of patients with myeloproliferative disorders.

References

1. Steensma DP. JAK2 V617F in Myeloid Disorders: Molecular Diagnostic Techniques and Their Clinical Utility. JMD. 2006;8(4):397-410.

2. Tefferi А, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22:14-22.

3. Yamaoka K, Saharinen P, Pesu M, Holt VE 3rd, Silvennoinen O, O’Shea JJ. The Janus kinases (Jaks). Genome Biology. 2004;5:253.

4. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6:372-375.

5. Wilson-Rawls J, Xie S, Liu J, Laneuville P, Arlinghaus RB. P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation. Cancer Res. 1996;56:3426-3430.

6. Spivak JL, Barosi G, Tognoni G, Barbui T, Finazzi G, Marchioli R, Marchetti M. Chronic myeloproliferative disorders. Hematology: American Society of Hematology Education Program Book. 2003:200-224.

7. McLornan D, Percy M, McMullin MF. JAK2 V617F: A Single Mutation in the Myeloproliferative Group of Disorders. Ulster Med J. 2006;75(2):112-119.

8. Tefferi А. Classification, Diagnosis and Management of Myeloproliferative Disorders in the JAK2V617F Era. Hematology. 2006;240-245.

9. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2V617F mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131(2):208-13.

10. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247:824-830.

11. Fiedler W, Henke RP, Ergün S, Schumacher U, Gehling UM, Vohwinkel G, Kilic N, Hossfeld DK. Derivation of a new hematopoietic cell line with endothelial features from a patient with transformed myeloproliferative syndrome: a case report. Cancer. 2000 Jan 15;88(2):344-51.

12. Lippert E, Girodon F, Hammond E, et al. Concordance of assays designed for the quantification of JAK2V617F: a multicenter study. Haematologica. 2008 Nov 10. Epub ahead of print.

13. Levine RL, Wernig G. Role of JAK-STAT Signaling in the Pathogenesis of Myeloproliferative Disorders. Hematology. 2006:233-239.

" ["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) "opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli" ["~CODE"]=> string(100) "opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli" ["EXTERNAL_ID"]=> string(3) "852" ["~EXTERNAL_ID"]=> string(3) "852" ["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(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["ELEMENT_META_KEYWORDS"]=> string(163) "миелопролиферативные заболевания мутация V617F в гене JAK2 полимеразная цепная реакция (ПЦР)" ["ELEMENT_META_DESCRIPTION"]=> string(310) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниямиDetecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(2451) "<p class="bodytext">Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.</p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_META_TITLE"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_META_KEYWORDS"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_META_DESCRIPTION"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_PICTURE_FILE_ALT"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_PICTURE_FILE_TITLE"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_PICTURE_FILE_NAME"]=> string(100) "opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli" ["SECTION_DETAIL_PICTURE_FILE_ALT"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_DETAIL_PICTURE_FILE_TITLE"]=> string(219) "Определение мутации V617F в гене JAK2 у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями" ["SECTION_DETAIL_PICTURE_FILE_NAME"]=> string(100) "opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli" ["ELEMENT_PREVIEW_PICTURE_FILE_NAME"]=> string(100) "opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli" ["ELEMENT_DETAIL_PICTURE_FILE_NAME"]=> string(100) "opredelenie-mutatsii-v617f-v-gene-jak2-u-patsientov-s-neverifitsirovannymi-khronicheskimi-mieloproli" } ["FIELDS"]=> array(1) { ["IBLOCK_SECTION_ID"]=> string(2) "34" } ["PROPERTIES"]=> array(18) { ["KEYWORDS"]=> array(36) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(3) { [0]=> string(5) "11700" [1]=> string(5) "11701" [2]=> string(5) "11702" } ["VALUE"]=> array(3) { [0]=> string(3) "850" [1]=> string(3) "851" [2]=> string(3) "711" } ["DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(3) { [0]=> string(3) "850" [1]=> string(3) "851" [2]=> string(3) "711" } ["~DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11658" ["VALUE"]=> string(22) "10/30/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "10/30/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11659" ["VALUE"]=> string(22) "12/11/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/11/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11660" ["VALUE"]=> string(22) "12/17/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/17/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL } ["CONTACT"]=> array(36) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11661" ["VALUE"]=> string(3) "849" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "849" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(5) { [0]=> string(5) "11703" [1]=> string(5) "11704" [2]=> string(5) "11705" [3]=> string(5) "11706" [4]=> string(5) "11707" } ["VALUE"]=> array(5) { [0]=> string(3) "845" [1]=> string(3) "846" [2]=> string(3) "847" [3]=> string(3) "848" [4]=> string(3) "849" } ["DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(5) { [0]=> string(3) "845" [1]=> string(3) "846" [2]=> string(3) "847" [3]=> string(3) "848" [4]=> string(3) "849" } ["~DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "11677" ["VALUE"]=> array(2) { ["TEXT"]=> string(169) "<p class="Autor">Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(147) "

Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.

" ["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) "11678" ["VALUE"]=> array(2) { ["TEXT"]=> string(2451) "<p class="bodytext">Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2429) "

Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11667" ["VALUE"]=> string(29) "10.3205/ctt-2008-en-000018.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2008-en-000018.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "11689" ["VALUE"]=> array(2) { ["TEXT"]=> string(138) "<p class="Autor">Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(116) "

Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "11690" ["VALUE"]=> array(2) { ["TEXT"]=> string(75) "<p>Saint-Petersburg Pavlov State Medical University, Russia</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(63) "

Saint-Petersburg Pavlov State Medical University, Russia

" ["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) "11691" ["VALUE"]=> array(2) { ["TEXT"]=> string(1272) "<p class="bodytext">Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1250) "

Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11668" ["VALUE"]=> string(91) "Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(91) "Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> &array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_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) "42" ["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(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11679" ["VALUE"]=> string(3) "500" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "500" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11680" ["VALUE"]=> string(3) "501" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "501" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["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) "45" ["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(80) } ["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(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(13) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "11689" ["VALUE"]=> array(2) { ["TEXT"]=> string(138) "<p class="Autor">Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(116) "

Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(116) "

Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy

" } ["SUMMARY_EN"]=> array(37) { ["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) "11691" ["VALUE"]=> array(2) { ["TEXT"]=> string(1272) "<p class="bodytext">Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1250) "

Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.

" ["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(1250) "

Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11667" ["VALUE"]=> string(29) "10.3205/ctt-2008-en-000018.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2008-en-000018.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(29) "10.3205/ctt-2008-en-000018.01" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11668" ["VALUE"]=> string(91) "Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(91) "Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(91) "Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "11690" ["VALUE"]=> array(2) { ["TEXT"]=> string(75) "<p>Saint-Petersburg Pavlov State Medical University, Russia</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(63) "

Saint-Petersburg Pavlov State Medical University, Russia

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(63) "

Saint-Petersburg Pavlov State Medical University, Russia

" } ["AUTHORS"]=> array(38) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(5) { [0]=> string(5) "11703" [1]=> string(5) "11704" [2]=> string(5) "11705" [3]=> string(5) "11706" [4]=> string(5) "11707" } ["VALUE"]=> array(5) { [0]=> string(3) "845" [1]=> string(3) "846" [2]=> string(3) "847" [3]=> string(3) "848" [4]=> string(3) "849" } ["DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(5) { [0]=> string(3) "845" [1]=> string(3) "846" [2]=> string(3) "847" [3]=> string(3) "848" [4]=> string(3) "849" } ["~DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(5) { [0]=> string(60) "Irina Y. Saburova" [1]=> string(60) "Yana S.Onikiychuk" [2]=> string(58) "Irina I. Zotova" [3]=> string(60) "Galina N. Sologub" [4]=> string(63) "Mikhail I. Zarayskiy" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "11677" ["VALUE"]=> array(2) { ["TEXT"]=> string(169) "<p class="Autor">Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(147) "

Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(147) "

Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.

" } ["SUBMITTED"]=> array(37) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11658" ["VALUE"]=> string(22) "10/30/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "10/30/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "10/30/2008 12:00:00 am" } ["ACCEPTED"]=> array(37) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11659" ["VALUE"]=> string(22) "12/11/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/11/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "12/11/2008 12:00:00 am" } ["PUBLISHED"]=> array(37) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11660" ["VALUE"]=> string(22) "12/17/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/17/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "12/17/2008 12:00:00 am" } ["KEYWORDS"]=> array(38) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(3) { [0]=> string(5) "11700" [1]=> string(5) "11701" [2]=> string(5) "11702" } ["VALUE"]=> array(3) { [0]=> string(3) "850" [1]=> string(3) "851" [2]=> string(3) "711" } ["DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(3) { [0]=> string(3) "850" [1]=> string(3) "851" [2]=> string(3) "711" } ["~DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(3) { [0]=> string(107) "миелопролиферативные заболевания" [1]=> string(81) "мутация V617F в гене JAK2" [2]=> string(105) "полимеразная цепная реакция (ПЦР)" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["CONTACT"]=> array(38) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11661" ["VALUE"]=> string(3) "849" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "849" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(63) "Mikhail I. Zarayskiy" ["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) "11678" ["VALUE"]=> array(2) { ["TEXT"]=> string(2451) "<p class="bodytext">Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2429) "

Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.

" ["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(2429) "

Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.

" } } } [1]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "34" ["~IBLOCK_SECTION_ID"]=> string(2) "34" ["ID"]=> string(3) "859" ["~ID"]=> string(3) "859" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["~NAME"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "06/15/2017 12:00:18 pm" ["~TIMESTAMP_X"]=> string(22) "06/15/2017 12:00:18 pm" ["DETAIL_PAGE_URL"]=> string(109) "/en/archive/Volume-1/stati/primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom/" ["~DETAIL_PAGE_URL"]=> string(109) "/en/archive/Volume-1/stati/primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(17545) "

Introduction

Chronic myeloid leukaemia (CML) has an annual worldwide incidence of 1/100,000, with a male: female ratio of 1.5:1. The incidence rises slowly with age to reach a median of about 60 years [1]. The median age of patients with CML in Nigeria and other African countries with a similar demographic pattern is 38 years [2, 3]. Fleming and Menendez reported that more native African patients under age 40 years suffer from CML than any other group in the world; this differential age incidence pattern of CML is believed to be due to the age distribution of African populations rather than any inherent biological characteristic [4]. In the USA however, the incidence of CML in the age group under 70 years is higher among the African-Americans than among any other racial/ethnic groups [5]. It is probable that a combination of environment and as yet unknown biological factors may account for the differential age incidence pattern of CML between the Blacks and the other races in USA.  

The advent of Imatinib, an orally available, small molecule signal transduction inhibitor (STI) that specifically targets protein tyrosine kinases (TKIs), in particular, the CML-related bcr-abl, has led to radical changes in the management of CML following the publication of several studies that confirmed superior clinical, haematologic and cytogenetic remissions when the drug was compared to IFN-α and ara-C in all phases of the disease [6-9]. Imatinib has become the first-line therapy for CML in the world,  allogeneic stem cell transplantation now being reserved mainly for younger patients with poor-risk disease or for those who are resistant to Imatinib and/ or second generation TKIs [8, 9]. With the availability of free Imatinib Mesylate in resource-poor countries (through donation from the Glivec international patient-assistance program [GIPAP]; www.maxaid.org), this drug has also become the first-line therapy for CML in Nigeria; a great relief for patients in resource-limited countries.

This report describes the results for patients with newly diagnosed CML in diverse phases of the disease that were treated with Imatinib.

Patients and Methods

Between August 2003 and August 2007, a total of 98 consenting adults and children, who had been diagnosed with CML, were commenced on Imatinib as part of the ongoing GIPAP treatment programme at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria. Eighty-four patients had been exposed to previous single-agent chemotherapy comprising: hydroxyurea (n = 79), busulphan (n = 5) and IFN-alfa (n = 5). Five patients had previously received concurrent multiple chemotherapeutic agents, including Cyclophosphamide, Oncovin, ara-C and prednisolone (COAP; n = 4) and Doxorubicin and ara-c (DA; n = 1). Participants were drawn from all parts of Nigeria. The diagnosis of CML was made according to the WHO standard clinical, haematologic and cytogenetic criteria [10], which has also been applied to the staging of the diseases in Imatinib era [11].

Chromosome analysis was done using cultured bone marrow aspirate samples; Philadelphia chromosome was estimated from at least 20 metaphases and the proportion of Ph+ cells was noted for each patient.

Patients in chronic phase received oral Imatinib: 400mg daily. Those in the accelerated or blastic phase received 600mg daily. Imatinib was continued for as long as there was evidence of continued benefit from therapy. Allopurinol (300 mg daily) was given until leucocyte count fell below 20 x 10⁹/L. Patients with hyperleucocytosis (leucocyte count > 100 x 10⁹/L), and on hydroxyurea, were continued on the latter for another 1-3 weeks, with monitoring of the full blood count before final withdrawal of the drug, when the white cell count fell to less than 100 x 10⁹/L.

In individuals with severe Imatinib-induced myelosuppression, the drug was withheld until the neutrophils rose to 1.5 x 10⁹/L and the platelets to at least 75 x 10⁹/L. Patients with recurrent, therapy-induced myelosuppression had the Imatinib dose reduced to 300mg daily until blood counts normalised (minimum dose for therapeutic blood levels in adults). However, if the myelosuppression was related to blastic transformation, Imatinib was continued with appropriate supportive therapy being given.

Response to therapy was assessed by clinical, haematologic and cytogenetic parameters as recommended by the expert panel of the European LeukemiaNet [12]. Clinical examination and full blood count monitoring were performed every 1-2 weeks for the first three months, until the blood count became stable, or until remission was achieved. Thereafter, patients were monitored every three months. Serum chemistry and cytogenetic analyses were evaluated every six months.

Previously published definitions of CP, AP and BP were used [10, 11]. Overall survival (OS) was the primary end-point and was defined as the interval between the date of commencement of Imatinib and the date of death or loss to follow-up. Secondary end-points were time to complete haematologic remission (CHR) and/or complete cytogenetic remission (CCR). CHR was defined as restoration of a normal blood count, with absence of blasts or promyelocytes, extramedullary deposits, or other signs of the disease. Cytogenetic response was checked every 6 months, by counting proportions of Ph+ cells from among not less than 20 metaphases, whilst definitions of complete, major, minor and no cytogenetic response (CCR (0% Ph+), MCR (1-34% Ph+),  mnCR (35-90 Ph+), and NCR (> 90% Ph+) and those for complete or major molecular response (CMR, MMR) were as previously described [12].

This study was conducted according to the declaration of Helsinki concerning patients' rights and confidentiality. Approval for the study was obtained from the OAUTHC ethical committee. All patients or their parents (in the case of minors) gave written informed consent.

The study is ongoing but for the purpose of this analysis, August 31st 2007 was taken as the cut-off, this being the date on which the first patient has been followed-up for 48 months. Analyses of OS and PFS were performed using the Kaplan-Meier method, by "intention-to-treat". Differences between subgroups of patients receiving Imatinib were analysed using the Log-rank test. SPSS for Windows 11 (SPSS Inc. 1981-2001, USA) and Microsoft Excel were used for all statistical calculations. The following pre-treatment variables were analysed for correlations with achievement of response, OS and PFS: age, gender, time of starting treatment and platelet count prior chemotherapy.

Results

This study was based on 98 patients, their ages ranging from 11 to 65 years (median = 36). There were 56 males and 42 females. The median time from diagnosis to treatment was 14.3 weeks (range 0-239 weeks). Seventy-eight (80%) and 40 (41%) of 98 patients presented with splenomegaly and/ or hepatomegaly, with a median size of 12cm and 7cm below the costal margin, respectively; 85 (86.7%) patients were in CP and 13 (13.2%) in AP/BP (12 and 1 respectively, Table 1).

Table 1. Patients’ characteristics at diagnosis

With a median follow-up of 25 months, 51 patients had repeat chromosome analysis at least 6 months into Glivec therapy; 30 (59%) and 18 (35%) achieved CCR and a MCR, respectively. 

Also notable was the fact that on completion of one and three months of Imatinib therapy, 53/83 (64%) and 58/70 (83%) of patients respectively were in complete haematologic remission (CHR).

Kaplan-Meier analysis of the relevant pre- and post-recruitment variables shows that commencement of Imatinib within 60 days of diagnosis,  and achievement of CHR within one month of commencing therapy were  predictive for achieving a CCR (p = 0.039 and 0.019 respectively; Table 2).

Table 2. Univariate analysis of patients characteristics, survival and cytogenetic remission.

p-Values in bold type are significant, those in regular type are close to significance. *The variables with the better outcomes are written first. Abbreviations: OS, overall survival; PFS, progression-free survival; SE, standard error; BCM, below the costal margin; LFU, last follow-up; ns, not significant; NA, not applicable; CHR, complete haematologic remission; CCR: complete cytogenetic remission; MCR: major cytogenetic remission; mCR: minor cytogenetic remission.

Kaplan-Meier estimates for OS and PFS at one year were 96% and 91%, respectively. At 40 months, the OS and PFS had dropped to 68% and 61%, respectively. Eighty-seven of the 98 patients overall (88.8%) remain alive, and are tolerating the drug well.

Also, achievement of CHR within 3 months or CCR within 6 months of commencing therapy predicted for better OS and PFS (CHR: p = 0.027, 0.011 respectively; CCR: p = 0.043, 0.045 respectively; Table 2). A statistically insignificant trend (p = 0.06) was observed for better OS in patients who did not experience myelosuppression (requiring cessation of the drug for ≥ 2 weeks) during the first 6 months of treatment. Eleven of the 44 patients (25%) who were in MCR/mnCR at six months had improved to CCR at the last follow-up.

Discussion

With a median follow-up of 25 months, these results demonstrate a CCR rate of 59%, which is the same as that reported by Kantarjian et al in a previous study with 18 months' follow-up [13]. The latter group of patients had however previously received IFN-α, whereas most of the Nigerian patients had been treated with hydroxyurea as first-line therapy. Overall, 80% of newly diagnosed patients with CML in chronic phase would be expected to achieve CCR with Imatinib [14]. In this study, relatively shorter survival was to be expected, since 21 patients were not in chronic phase at the time of starting treatment, and responses are known to be less durable in AP and almost always transient in BP [8, 15, 16].

The median time from diagnosis to commencement of Imatinib was relatively long, at 14.3 weeks (range 0-239 weeks) and it is known that this can worsen the prognosis and reduce the probability of response. Nonetheless, the relatively high survival (96%, SE = 0.022) at one year is impressive for an African population of patients, although obviously, this value will fall with longer follow-up, with 68.3% at 40 months. The extended IRIS study has recently reported a 5-year overall survival estimate of 89% [17] and several studies have demonstrated significant survival differences based on the Sokal and/or Hasford risk groups at diagnosis [14, 15, 18-20]. However, these parameters could not be evaluated since initial data (at diagnosis) on the majority of our patients were unavailable.

The survival advantage observed for patients in whom CCR was achieved by six months is an important finding since it confirms the efficacy of Imatinib, an observation that has not been reported in native sub-Saharan Africans before. This pioneering work has shown that outcome of Imatinib therapy for Ph+ CML in native Nigerians is no different from reports in the Western populations.

We conclude that Imatinib in Nigerian patients with CML is very promising with the additional advantages of oral availability and tolerability, both of which make the drug highly acceptable.

Acknowledgements

We are grateful to Novartis for providing Imatinib mesylate (Glivec), to the Max Foundation and Axios International for facilitating the delivery of the drug, to the Federal Government and NAFDAC for facilitating customs clearance of the drug. We are also indebted to all the faculty and staff of the Department of Haematology, Obafemi Awolowo University (OAU) and OAU Teaching Hospitals Complex, Ile-Ife for the care of the patients involved in this study. We are especially grateful to the nursing staff. Professor Ama Rohatiner of the St. Baths Hospital, London, kindly reviewed the manuscript.

References

1. Deninger MWN, Druker BJ. Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib. Pharmacol Rev. 2003;55:401-423.

2. Boma PO, Durosinmi MA, Adediran IA, Akinola NO, Salawu L. Clinical and prognostic features of Nigerians with chronic myeloid leukemia. Niger Postgrad Med J. 2006;13:47-52.

3. Okanny CC, Akinyanju OO. Chronic leukaemia: an African experience. Med Oncol Tumor Pharmacother. 1989;6:189-194.

4. Fleming AF, Menendez C. Blood. In: Parry E, Godfrey R, Mabey D, Gill G, eds. Principles of Medicine in Africa. Vol. 78. Cambridge, United Kingdom; 2004:961.

5. Groves FD, Linet MS, Devesa SS. Patterns of occurrence of the leukaemias. Eur J Cancer. 1995;31A:941-994.

6. Deininger MWN, O'Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving Imatinib. J Clin Oncol. 2003;21:1637-1647.

7. Melo JV, Hughes TP, Apperley JF. Chronic myeloid leukemia. ASH Hematology. 2003:132-152.

8. Shah NP. Loss of Response to Imatinib: Mechanisms and Management. Hematology. 2005;2005:183-187.

9. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor. Science. 2004;305:399-401.

10. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–2302.

11. Cortes JE, Talpaz M, O’Brien S, et al. Staging of Chronic Myeloid Leukemia in the Imatinib Era: An Evaluation of the World Health Organization Proposal. Cancer. 2006;106:1306–1315.

12. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809–1820.

13. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645-652.

14. Deininger MWN. Chronic myeloid leukemia: Management of Early Stage Disease. ASH Hematology. 2005:174-182.

15. Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876-880.

16. O'Brien S, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994-1008.

17. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99:1928-1937.

18. Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850-858.

19. Sneed TB, Kantarjian HM, Talpaz M, et al. The Significance of Myelosuppression during Therapy with Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia in Chronic Phase. Cancer. 2004;100:116–121.

20. Sokal JE, Cox EB, Baccarani M, et al. Prognostic Discrimination in “Good Risk” Chronic Granulocytic Leukemia. Blood. 1984;63:789-799.

" ["~DETAIL_TEXT"]=> string(17545) "

Introduction

Chronic myeloid leukaemia (CML) has an annual worldwide incidence of 1/100,000, with a male: female ratio of 1.5:1. The incidence rises slowly with age to reach a median of about 60 years [1]. The median age of patients with CML in Nigeria and other African countries with a similar demographic pattern is 38 years [2, 3]. Fleming and Menendez reported that more native African patients under age 40 years suffer from CML than any other group in the world; this differential age incidence pattern of CML is believed to be due to the age distribution of African populations rather than any inherent biological characteristic [4]. In the USA however, the incidence of CML in the age group under 70 years is higher among the African-Americans than among any other racial/ethnic groups [5]. It is probable that a combination of environment and as yet unknown biological factors may account for the differential age incidence pattern of CML between the Blacks and the other races in USA.  

The advent of Imatinib, an orally available, small molecule signal transduction inhibitor (STI) that specifically targets protein tyrosine kinases (TKIs), in particular, the CML-related bcr-abl, has led to radical changes in the management of CML following the publication of several studies that confirmed superior clinical, haematologic and cytogenetic remissions when the drug was compared to IFN-α and ara-C in all phases of the disease [6-9]. Imatinib has become the first-line therapy for CML in the world,  allogeneic stem cell transplantation now being reserved mainly for younger patients with poor-risk disease or for those who are resistant to Imatinib and/ or second generation TKIs [8, 9]. With the availability of free Imatinib Mesylate in resource-poor countries (through donation from the Glivec international patient-assistance program [GIPAP]; www.maxaid.org), this drug has also become the first-line therapy for CML in Nigeria; a great relief for patients in resource-limited countries.

This report describes the results for patients with newly diagnosed CML in diverse phases of the disease that were treated with Imatinib.

Patients and Methods

Between August 2003 and August 2007, a total of 98 consenting adults and children, who had been diagnosed with CML, were commenced on Imatinib as part of the ongoing GIPAP treatment programme at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria. Eighty-four patients had been exposed to previous single-agent chemotherapy comprising: hydroxyurea (n = 79), busulphan (n = 5) and IFN-alfa (n = 5). Five patients had previously received concurrent multiple chemotherapeutic agents, including Cyclophosphamide, Oncovin, ara-C and prednisolone (COAP; n = 4) and Doxorubicin and ara-c (DA; n = 1). Participants were drawn from all parts of Nigeria. The diagnosis of CML was made according to the WHO standard clinical, haematologic and cytogenetic criteria [10], which has also been applied to the staging of the diseases in Imatinib era [11].

Chromosome analysis was done using cultured bone marrow aspirate samples; Philadelphia chromosome was estimated from at least 20 metaphases and the proportion of Ph+ cells was noted for each patient.

Patients in chronic phase received oral Imatinib: 400mg daily. Those in the accelerated or blastic phase received 600mg daily. Imatinib was continued for as long as there was evidence of continued benefit from therapy. Allopurinol (300 mg daily) was given until leucocyte count fell below 20 x 10⁹/L. Patients with hyperleucocytosis (leucocyte count > 100 x 10⁹/L), and on hydroxyurea, were continued on the latter for another 1-3 weeks, with monitoring of the full blood count before final withdrawal of the drug, when the white cell count fell to less than 100 x 10⁹/L.

In individuals with severe Imatinib-induced myelosuppression, the drug was withheld until the neutrophils rose to 1.5 x 10⁹/L and the platelets to at least 75 x 10⁹/L. Patients with recurrent, therapy-induced myelosuppression had the Imatinib dose reduced to 300mg daily until blood counts normalised (minimum dose for therapeutic blood levels in adults). However, if the myelosuppression was related to blastic transformation, Imatinib was continued with appropriate supportive therapy being given.

Response to therapy was assessed by clinical, haematologic and cytogenetic parameters as recommended by the expert panel of the European LeukemiaNet [12]. Clinical examination and full blood count monitoring were performed every 1-2 weeks for the first three months, until the blood count became stable, or until remission was achieved. Thereafter, patients were monitored every three months. Serum chemistry and cytogenetic analyses were evaluated every six months.

Previously published definitions of CP, AP and BP were used [10, 11]. Overall survival (OS) was the primary end-point and was defined as the interval between the date of commencement of Imatinib and the date of death or loss to follow-up. Secondary end-points were time to complete haematologic remission (CHR) and/or complete cytogenetic remission (CCR). CHR was defined as restoration of a normal blood count, with absence of blasts or promyelocytes, extramedullary deposits, or other signs of the disease. Cytogenetic response was checked every 6 months, by counting proportions of Ph+ cells from among not less than 20 metaphases, whilst definitions of complete, major, minor and no cytogenetic response (CCR (0% Ph+), MCR (1-34% Ph+),  mnCR (35-90 Ph+), and NCR (> 90% Ph+) and those for complete or major molecular response (CMR, MMR) were as previously described [12].

This study was conducted according to the declaration of Helsinki concerning patients' rights and confidentiality. Approval for the study was obtained from the OAUTHC ethical committee. All patients or their parents (in the case of minors) gave written informed consent.

The study is ongoing but for the purpose of this analysis, August 31st 2007 was taken as the cut-off, this being the date on which the first patient has been followed-up for 48 months. Analyses of OS and PFS were performed using the Kaplan-Meier method, by "intention-to-treat". Differences between subgroups of patients receiving Imatinib were analysed using the Log-rank test. SPSS for Windows 11 (SPSS Inc. 1981-2001, USA) and Microsoft Excel were used for all statistical calculations. The following pre-treatment variables were analysed for correlations with achievement of response, OS and PFS: age, gender, time of starting treatment and platelet count prior chemotherapy.

Results

This study was based on 98 patients, their ages ranging from 11 to 65 years (median = 36). There were 56 males and 42 females. The median time from diagnosis to treatment was 14.3 weeks (range 0-239 weeks). Seventy-eight (80%) and 40 (41%) of 98 patients presented with splenomegaly and/ or hepatomegaly, with a median size of 12cm and 7cm below the costal margin, respectively; 85 (86.7%) patients were in CP and 13 (13.2%) in AP/BP (12 and 1 respectively, Table 1).

Table 1. Patients’ characteristics at diagnosis

With a median follow-up of 25 months, 51 patients had repeat chromosome analysis at least 6 months into Glivec therapy; 30 (59%) and 18 (35%) achieved CCR and a MCR, respectively. 

Also notable was the fact that on completion of one and three months of Imatinib therapy, 53/83 (64%) and 58/70 (83%) of patients respectively were in complete haematologic remission (CHR).

Kaplan-Meier analysis of the relevant pre- and post-recruitment variables shows that commencement of Imatinib within 60 days of diagnosis,  and achievement of CHR within one month of commencing therapy were  predictive for achieving a CCR (p = 0.039 and 0.019 respectively; Table 2).

Table 2. Univariate analysis of patients characteristics, survival and cytogenetic remission.

p-Values in bold type are significant, those in regular type are close to significance. *The variables with the better outcomes are written first. Abbreviations: OS, overall survival; PFS, progression-free survival; SE, standard error; BCM, below the costal margin; LFU, last follow-up; ns, not significant; NA, not applicable; CHR, complete haematologic remission; CCR: complete cytogenetic remission; MCR: major cytogenetic remission; mCR: minor cytogenetic remission.

Kaplan-Meier estimates for OS and PFS at one year were 96% and 91%, respectively. At 40 months, the OS and PFS had dropped to 68% and 61%, respectively. Eighty-seven of the 98 patients overall (88.8%) remain alive, and are tolerating the drug well.

Also, achievement of CHR within 3 months or CCR within 6 months of commencing therapy predicted for better OS and PFS (CHR: p = 0.027, 0.011 respectively; CCR: p = 0.043, 0.045 respectively; Table 2). A statistically insignificant trend (p = 0.06) was observed for better OS in patients who did not experience myelosuppression (requiring cessation of the drug for ≥ 2 weeks) during the first 6 months of treatment. Eleven of the 44 patients (25%) who were in MCR/mnCR at six months had improved to CCR at the last follow-up.

Discussion

With a median follow-up of 25 months, these results demonstrate a CCR rate of 59%, which is the same as that reported by Kantarjian et al in a previous study with 18 months' follow-up [13]. The latter group of patients had however previously received IFN-α, whereas most of the Nigerian patients had been treated with hydroxyurea as first-line therapy. Overall, 80% of newly diagnosed patients with CML in chronic phase would be expected to achieve CCR with Imatinib [14]. In this study, relatively shorter survival was to be expected, since 21 patients were not in chronic phase at the time of starting treatment, and responses are known to be less durable in AP and almost always transient in BP [8, 15, 16].

The median time from diagnosis to commencement of Imatinib was relatively long, at 14.3 weeks (range 0-239 weeks) and it is known that this can worsen the prognosis and reduce the probability of response. Nonetheless, the relatively high survival (96%, SE = 0.022) at one year is impressive for an African population of patients, although obviously, this value will fall with longer follow-up, with 68.3% at 40 months. The extended IRIS study has recently reported a 5-year overall survival estimate of 89% [17] and several studies have demonstrated significant survival differences based on the Sokal and/or Hasford risk groups at diagnosis [14, 15, 18-20]. However, these parameters could not be evaluated since initial data (at diagnosis) on the majority of our patients were unavailable.

The survival advantage observed for patients in whom CCR was achieved by six months is an important finding since it confirms the efficacy of Imatinib, an observation that has not been reported in native sub-Saharan Africans before. This pioneering work has shown that outcome of Imatinib therapy for Ph+ CML in native Nigerians is no different from reports in the Western populations.

We conclude that Imatinib in Nigerian patients with CML is very promising with the additional advantages of oral availability and tolerability, both of which make the drug highly acceptable.

Acknowledgements

We are grateful to Novartis for providing Imatinib mesylate (Glivec), to the Max Foundation and Axios International for facilitating the delivery of the drug, to the Federal Government and NAFDAC for facilitating customs clearance of the drug. We are also indebted to all the faculty and staff of the Department of Haematology, Obafemi Awolowo University (OAU) and OAU Teaching Hospitals Complex, Ile-Ife for the care of the patients involved in this study. We are especially grateful to the nursing staff. Professor Ama Rohatiner of the St. Baths Hospital, London, kindly reviewed the manuscript.

References

1. Deninger MWN, Druker BJ. Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib. Pharmacol Rev. 2003;55:401-423.

2. Boma PO, Durosinmi MA, Adediran IA, Akinola NO, Salawu L. Clinical and prognostic features of Nigerians with chronic myeloid leukemia. Niger Postgrad Med J. 2006;13:47-52.

3. Okanny CC, Akinyanju OO. Chronic leukaemia: an African experience. Med Oncol Tumor Pharmacother. 1989;6:189-194.

4. Fleming AF, Menendez C. Blood. In: Parry E, Godfrey R, Mabey D, Gill G, eds. Principles of Medicine in Africa. Vol. 78. Cambridge, United Kingdom; 2004:961.

5. Groves FD, Linet MS, Devesa SS. Patterns of occurrence of the leukaemias. Eur J Cancer. 1995;31A:941-994.

6. Deininger MWN, O'Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving Imatinib. J Clin Oncol. 2003;21:1637-1647.

7. Melo JV, Hughes TP, Apperley JF. Chronic myeloid leukemia. ASH Hematology. 2003:132-152.

8. Shah NP. Loss of Response to Imatinib: Mechanisms and Management. Hematology. 2005;2005:183-187.

9. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor. Science. 2004;305:399-401.

10. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–2302.

11. Cortes JE, Talpaz M, O’Brien S, et al. Staging of Chronic Myeloid Leukemia in the Imatinib Era: An Evaluation of the World Health Organization Proposal. Cancer. 2006;106:1306–1315.

12. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809–1820.

13. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645-652.

14. Deininger MWN. Chronic myeloid leukemia: Management of Early Stage Disease. ASH Hematology. 2005:174-182.

15. Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876-880.

16. O'Brien S, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994-1008.

17. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99:1928-1937.

18. Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850-858.

19. Sneed TB, Kantarjian HM, Talpaz M, et al. The Significance of Myelosuppression during Therapy with Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia in Chronic Phase. Cancer. 2004;100:116–121.

20. Sokal JE, Cox EB, Baccarani M, et al. Prognostic Discrimination in “Good Risk” Chronic Granulocytic Leukemia. Blood. 1984;63:789-799.

" ["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(81) "primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom" ["~CODE"]=> string(81) "primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom" ["EXTERNAL_ID"]=> string(3) "859" ["~EXTERNAL_ID"]=> string(3) "859" ["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(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["ELEMENT_META_KEYWORDS"]=> string(142) "иматиниб мезилат хронический миелолейкоз цитогенетическая ремиссия Нигерия" ["ELEMENT_META_DESCRIPTION"]=> string(221) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозомThe use of Imatinib mesylate in Nigerians with chronic myeloid leukemia" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(3404) "<h3>Цель работы</h3> <p>Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).</p> <h3> Методы и клинический материал</h3> <p> С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток). <br /> <h3>Результаты</h3> <p> После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043). <br /><h3>Выводы</h3> <p>В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях. </p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_META_TITLE"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_META_KEYWORDS"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_META_DESCRIPTION"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_PICTURE_FILE_ALT"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_PICTURE_FILE_TITLE"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_PICTURE_FILE_NAME"]=> string(85) "primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom-img" ["SECTION_DETAIL_PICTURE_FILE_ALT"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_DETAIL_PICTURE_FILE_TITLE"]=> string(150) "Применение Иматиниба мезилата (Гливека) у нигерийцев с хроническим миелолейкозом" ["SECTION_DETAIL_PICTURE_FILE_NAME"]=> string(85) "primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom-img" ["ELEMENT_PREVIEW_PICTURE_FILE_NAME"]=> string(85) "primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom-img" ["ELEMENT_DETAIL_PICTURE_FILE_NAME"]=> string(85) "primenenie-imatiniba-mezilata-gliveka-u-nigeriytsev-s-khronicheskim-mieloleykozom-img" } ["FIELDS"]=> array(1) { ["IBLOCK_SECTION_ID"]=> string(2) "34" } ["PROPERTIES"]=> array(18) { ["KEYWORDS"]=> array(36) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(4) { [0]=> string(5) "11914" [1]=> string(5) "11915" [2]=> string(5) "11916" [3]=> string(5) "11917" } ["VALUE"]=> array(4) { [0]=> string(3) "856" [1]=> string(3) "163" [2]=> string(3) "857" [3]=> string(3) "858" } ["DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(4) { [0]=> string(3) "856" [1]=> string(3) "163" [2]=> string(3) "857" [3]=> string(3) "858" } ["~DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11742" ["VALUE"]=> string(22) "08/28/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "08/28/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11743" ["VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11744" ["VALUE"]=> string(22) "12/15/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/15/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL } ["CONTACT"]=> array(36) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11745" ["VALUE"]=> string(3) "853" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "853" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(3) { [0]=> string(5) "11918" [1]=> string(5) "11919" [2]=> string(5) "11920" } ["VALUE"]=> array(3) { [0]=> string(3) "853" [1]=> string(3) "854" [2]=> string(3) "855" } ["DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(3) { [0]=> string(3) "853" [1]=> string(3) "854" [2]=> string(3) "855" } ["~DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "11758" ["VALUE"]=> array(2) { ["TEXT"]=> string(134) "<p class="Autor">Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(112) "

Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.

" ["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) "11759" ["VALUE"]=> array(2) { ["TEXT"]=> string(3404) "<h3>Цель работы</h3> <p>Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).</p> <h3> Методы и клинический материал</h3> <p> С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток). <br /> <h3>Результаты</h3> <p> После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043). <br /><h3>Выводы</h3> <p>В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3308) "

Цель работы

Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).

Методы и клинический материал

С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток).

Результаты

После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043).

Выводы

В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11749" ["VALUE"]=> string(29) "10.3205/ctt-2008-en-000027.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2008-en-000027.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "11769" ["VALUE"]=> array(2) { ["TEXT"]=> string(1495) "<p class="Autor">Prof. Muheez A. Durosinmi¹, Prof. Julius O. Faluyi², Dr. Anthony A. Oyekunle¹, Dr. Lateef Salawu¹, Dr. Ismail A. Adediran¹, Dr. Norah O. Akinola¹, Oluwakemi O. Bamgbade³, Dr. Charles C. Okanny⁴, Dr. Sulaiman Akanmu⁴, Dr. Oche P. Ogbe⁵, Dr. Tambi T. Wakama⁵, Dr. Chijoke A. Nwauche⁶, Dr. Matthew E. Enosolease⁷, Dr. Daye N.K. Halim⁷, Dr. Godwin N. Bazuaye⁷, Dr. Chide E. Okocha⁸, Dr. J. A. Olaniyi⁹, Dr. Titi S. Akingbola⁹, Dr. Victor O. Mabayoje¹⁰, Dr. Ajani A. Raji¹⁰, Dr. Aisha Mamman¹¹, Dr. Aisha Kuliya-Gwarzo¹², Dr. Obike G. Ibegbulam¹³, Dr. Sunday Ocheni¹³, Dr. Yohanna Tanko¹⁴, Dr. Oladimeji P. Arewa¹, Dr. Rahman A.A. Bolarinwa¹, Dr. Davidson O. Kassim¹, Dr. Mohammed A. Ndakotsu¹, Dr. Omotilewa A. Amusu¹⁵, Prof. O. O. Akinyanju¹⁶</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1101) "

Prof. Muheez A. Durosinmi¹, Prof. Julius O. Faluyi², Dr. Anthony A. Oyekunle¹, Dr. Lateef Salawu¹, Dr. Ismail A. Adediran¹, Dr. Norah O. Akinola¹, Oluwakemi O. Bamgbade³, Dr. Charles C. Okanny⁴, Dr. Sulaiman Akanmu⁴, Dr. Oche P. Ogbe⁵, Dr. Tambi T. Wakama⁵, Dr. Chijoke A. Nwauche⁶, Dr. Matthew E. Enosolease⁷, Dr. Daye N.K. Halim⁷, Dr. Godwin N. Bazuaye⁷, Dr. Chide E. Okocha⁸, Dr. J. A. Olaniyi⁹, Dr. Titi S. Akingbola⁹, Dr. Victor O. Mabayoje¹⁰, Dr. Ajani A. Raji¹⁰, Dr. Aisha Mamman¹¹, Dr. Aisha Kuliya-Gwarzo¹², Dr. Obike G. Ibegbulam¹³, Dr. Sunday Ocheni¹³, Dr. Yohanna Tanko¹⁴, Dr. Oladimeji P. Arewa¹, Dr. Rahman A.A. Bolarinwa¹, Dr. Davidson O. Kassim¹, Dr. Mohammed A. Ndakotsu¹, Dr. Omotilewa A. Amusu¹⁵, Prof. O. O. Akinyanju¹⁶

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "11770" ["VALUE"]=> array(2) { ["TEXT"]=> string(1583) "<p class="bodytext">¹Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; ²Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; ³Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; ⁴Department of Haematology, University of Lagos, Nigeria; ⁵Department of Haematology, National Hospital, Abuja, Nigeria; ⁶Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; ⁷Department of Haematology, University of Benin, Nigeria; ⁸Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; ⁹Department of Haematology, University College Hospital, Ibadan, Nigeria; ¹⁰Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; ¹¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, ¹²Department of Haematology, Bayero University,  Kano, Nigeria; ¹³Department of Haematology, University of Nigeria, Enugu, Nigeria; ¹⁴Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; ¹⁵Department of Haematology, Army Reference Hospital, Lagos, Nigeria; ¹⁶Asaju Medical Clinic, Victoria Island, Lagos, Nigeria</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1369) "

¹Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; ²Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; ³Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; ⁴Department of Haematology, University of Lagos, Nigeria; ⁵Department of Haematology, National Hospital, Abuja, Nigeria; ⁶Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; ⁷Department of Haematology, University of Benin, Nigeria; ⁸Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; ⁹Department of Haematology, University College Hospital, Ibadan, Nigeria; ¹⁰Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; ¹¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, ¹²Department of Haematology, Bayero University,  Kano, Nigeria; ¹³Department of Haematology, University of Nigeria, Enugu, Nigeria; ¹⁴Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; ¹⁵Department of Haematology, Army Reference Hospital, Lagos, Nigeria; ¹⁶Asaju Medical Clinic, Victoria Island, Lagos, Nigeria

" ["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) "11778" ["VALUE"]=> array(2) { ["TEXT"]=> string(1642) "<h3>Objectives</h3> <p>To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia. <br /></p> <h3>Methods</h3> <p>From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  </p> <h3>Results</h3> <p>Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043). </p> <h3>Conclusions</h3> <p>Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1540) "

Objectives

To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia.

Methods

From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  

Results

Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043).

Conclusions

Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11750" ["VALUE"]=> string(71) "The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(71) "The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_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) "42" ["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(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11760" ["VALUE"]=> string(3) "504" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "504" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11761" ["VALUE"]=> string(3) "505" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "505" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["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) "45" ["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(80) } ["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(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(13) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "11769" ["VALUE"]=> array(2) { ["TEXT"]=> string(1495) "<p class="Autor">Prof. Muheez A. Durosinmi¹, Prof. Julius O. Faluyi², Dr. Anthony A. Oyekunle¹, Dr. Lateef Salawu¹, Dr. Ismail A. Adediran¹, Dr. Norah O. Akinola¹, Oluwakemi O. Bamgbade³, Dr. Charles C. Okanny⁴, Dr. Sulaiman Akanmu⁴, Dr. Oche P. Ogbe⁵, Dr. Tambi T. Wakama⁵, Dr. Chijoke A. Nwauche⁶, Dr. Matthew E. Enosolease⁷, Dr. Daye N.K. Halim⁷, Dr. Godwin N. Bazuaye⁷, Dr. Chide E. Okocha⁸, Dr. J. A. Olaniyi⁹, Dr. Titi S. Akingbola⁹, Dr. Victor O. Mabayoje¹⁰, Dr. Ajani A. Raji¹⁰, Dr. Aisha Mamman¹¹, Dr. Aisha Kuliya-Gwarzo¹², Dr. Obike G. Ibegbulam¹³, Dr. Sunday Ocheni¹³, Dr. Yohanna Tanko¹⁴, Dr. Oladimeji P. Arewa¹, Dr. Rahman A.A. Bolarinwa¹, Dr. Davidson O. Kassim¹, Dr. Mohammed A. Ndakotsu¹, Dr. Omotilewa A. Amusu¹⁵, Prof. O. O. Akinyanju¹⁶</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1101) "

Prof. Muheez A. Durosinmi¹, Prof. Julius O. Faluyi², Dr. Anthony A. Oyekunle¹, Dr. Lateef Salawu¹, Dr. Ismail A. Adediran¹, Dr. Norah O. Akinola¹, Oluwakemi O. Bamgbade³, Dr. Charles C. Okanny⁴, Dr. Sulaiman Akanmu⁴, Dr. Oche P. Ogbe⁵, Dr. Tambi T. Wakama⁵, Dr. Chijoke A. Nwauche⁶, Dr. Matthew E. Enosolease⁷, Dr. Daye N.K. Halim⁷, Dr. Godwin N. Bazuaye⁷, Dr. Chide E. Okocha⁸, Dr. J. A. Olaniyi⁹, Dr. Titi S. Akingbola⁹, Dr. Victor O. Mabayoje¹⁰, Dr. Ajani A. Raji¹⁰, Dr. Aisha Mamman¹¹, Dr. Aisha Kuliya-Gwarzo¹², Dr. Obike G. Ibegbulam¹³, Dr. Sunday Ocheni¹³, Dr. Yohanna Tanko¹⁴, Dr. Oladimeji P. Arewa¹, Dr. Rahman A.A. Bolarinwa¹, Dr. Davidson O. Kassim¹, Dr. Mohammed A. Ndakotsu¹, Dr. Omotilewa A. Amusu¹⁵, Prof. O. O. Akinyanju¹⁶

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(1101) "

Prof. Muheez A. Durosinmi¹, Prof. Julius O. Faluyi², Dr. Anthony A. Oyekunle¹, Dr. Lateef Salawu¹, Dr. Ismail A. Adediran¹, Dr. Norah O. Akinola¹, Oluwakemi O. Bamgbade³, Dr. Charles C. Okanny⁴, Dr. Sulaiman Akanmu⁴, Dr. Oche P. Ogbe⁵, Dr. Tambi T. Wakama⁵, Dr. Chijoke A. Nwauche⁶, Dr. Matthew E. Enosolease⁷, Dr. Daye N.K. Halim⁷, Dr. Godwin N. Bazuaye⁷, Dr. Chide E. Okocha⁸, Dr. J. A. Olaniyi⁹, Dr. Titi S. Akingbola⁹, Dr. Victor O. Mabayoje¹⁰, Dr. Ajani A. Raji¹⁰, Dr. Aisha Mamman¹¹, Dr. Aisha Kuliya-Gwarzo¹², Dr. Obike G. Ibegbulam¹³, Dr. Sunday Ocheni¹³, Dr. Yohanna Tanko¹⁴, Dr. Oladimeji P. Arewa¹, Dr. Rahman A.A. Bolarinwa¹, Dr. Davidson O. Kassim¹, Dr. Mohammed A. Ndakotsu¹, Dr. Omotilewa A. Amusu¹⁵, Prof. O. O. Akinyanju¹⁶

" } ["SUMMARY_EN"]=> array(37) { ["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) "11778" ["VALUE"]=> array(2) { ["TEXT"]=> string(1642) "<h3>Objectives</h3> <p>To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia. <br /></p> <h3>Methods</h3> <p>From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  </p> <h3>Results</h3> <p>Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043). </p> <h3>Conclusions</h3> <p>Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1540) "

Objectives

To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia.

Methods

From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  

Results

Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043).

Conclusions

Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.

" ["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(1540) "

Objectives

To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia.

Methods

From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  

Results

Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043).

Conclusions

Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11749" ["VALUE"]=> string(29) "10.3205/ctt-2008-en-000027.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2008-en-000027.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(29) "10.3205/ctt-2008-en-000027.01" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11750" ["VALUE"]=> string(71) "The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(71) "The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(71) "The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "11770" ["VALUE"]=> array(2) { ["TEXT"]=> string(1583) "<p class="bodytext">¹Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; ²Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; ³Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; ⁴Department of Haematology, University of Lagos, Nigeria; ⁵Department of Haematology, National Hospital, Abuja, Nigeria; ⁶Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; ⁷Department of Haematology, University of Benin, Nigeria; ⁸Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; ⁹Department of Haematology, University College Hospital, Ibadan, Nigeria; ¹⁰Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; ¹¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, ¹²Department of Haematology, Bayero University,  Kano, Nigeria; ¹³Department of Haematology, University of Nigeria, Enugu, Nigeria; ¹⁴Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; ¹⁵Department of Haematology, Army Reference Hospital, Lagos, Nigeria; ¹⁶Asaju Medical Clinic, Victoria Island, Lagos, Nigeria</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1369) "

¹Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; ²Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; ³Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; ⁴Department of Haematology, University of Lagos, Nigeria; ⁵Department of Haematology, National Hospital, Abuja, Nigeria; ⁶Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; ⁷Department of Haematology, University of Benin, Nigeria; ⁸Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; ⁹Department of Haematology, University College Hospital, Ibadan, Nigeria; ¹⁰Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; ¹¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, ¹²Department of Haematology, Bayero University,  Kano, Nigeria; ¹³Department of Haematology, University of Nigeria, Enugu, Nigeria; ¹⁴Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; ¹⁵Department of Haematology, Army Reference Hospital, Lagos, Nigeria; ¹⁶Asaju Medical Clinic, Victoria Island, Lagos, Nigeria

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(1369) "

¹Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; ²Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; ³Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; ⁴Department of Haematology, University of Lagos, Nigeria; ⁵Department of Haematology, National Hospital, Abuja, Nigeria; ⁶Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; ⁷Department of Haematology, University of Benin, Nigeria; ⁸Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; ⁹Department of Haematology, University College Hospital, Ibadan, Nigeria; ¹⁰Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; ¹¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, ¹²Department of Haematology, Bayero University,  Kano, Nigeria; ¹³Department of Haematology, University of Nigeria, Enugu, Nigeria; ¹⁴Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; ¹⁵Department of Haematology, Army Reference Hospital, Lagos, Nigeria; ¹⁶Asaju Medical Clinic, Victoria Island, Lagos, Nigeria

" } ["AUTHORS"]=> array(38) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(3) { [0]=> string(5) "11918" [1]=> string(5) "11919" [2]=> string(5) "11920" } ["VALUE"]=> array(3) { [0]=> string(3) "853" [1]=> string(3) "854" [2]=> string(3) "855" } ["DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(3) { [0]=> string(3) "853" [1]=> string(3) "854" [2]=> string(3) "855" } ["~DESCRIPTION"]=> array(3) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(3) { [0]=> string(62) "Muheez A. Durosinmi" [1]=> string(59) "Julius O. Faluyi" [2]=> string(62) "Anthony A. Oyekunle" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "11758" ["VALUE"]=> array(2) { ["TEXT"]=> string(134) "<p class="Autor">Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(112) "

Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(112) "

Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.

" } ["SUBMITTED"]=> array(37) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11742" ["VALUE"]=> string(22) "08/28/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "08/28/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "08/28/2008 12:00:00 am" } ["ACCEPTED"]=> array(37) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11743" ["VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "11/21/2008 12:00:00 am" } ["PUBLISHED"]=> array(37) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11744" ["VALUE"]=> string(22) "12/15/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/15/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "12/15/2008 12:00:00 am" } ["KEYWORDS"]=> array(38) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(4) { [0]=> string(5) "11914" [1]=> string(5) "11915" [2]=> string(5) "11916" [3]=> string(5) "11917" } ["VALUE"]=> array(4) { [0]=> string(3) "856" [1]=> string(3) "163" [2]=> string(3) "857" [3]=> string(3) "858" } ["DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(4) { [0]=> string(3) "856" [1]=> string(3) "163" [2]=> string(3) "857" [3]=> string(3) "858" } ["~DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(4) { [0]=> string(75) "иматиниб мезилат" [1]=> string(89) "хронический миелолейкоз" [2]=> string(93) "цитогенетическая ремиссия" [3]=> string(58) "Нигерия" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["CONTACT"]=> array(38) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11745" ["VALUE"]=> string(3) "853" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "853" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(62) "Muheez A. Durosinmi" ["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) "11759" ["VALUE"]=> array(2) { ["TEXT"]=> string(3404) "<h3>Цель работы</h3> <p>Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).</p> <h3> Методы и клинический материал</h3> <p> С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток). <br /> <h3>Результаты</h3> <p> После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043). <br /><h3>Выводы</h3> <p>В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3308) "

Цель работы

Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).

Методы и клинический материал

С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток).

Результаты

После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043).

Выводы

В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях.

" ["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(3308) "

Цель работы

Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).

Методы и клинический материал

С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток).

Результаты

После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043).

Выводы

В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях.

" } } } [2]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "34" ["~IBLOCK_SECTION_ID"]=> string(2) "34" ["ID"]=> string(3) "866" ["~ID"]=> string(3) "866" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["~NAME"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "06/14/2017 03:47:24 pm" ["~TIMESTAMP_X"]=> string(22) "06/14/2017 03:47:24 pm" ["DETAIL_PAGE_URL"]=> string(111) "/en/archive/Volume-1/stati/vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer/" ["~DETAIL_PAGE_URL"]=> string(111) "/en/archive/Volume-1/stati/vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(24192) "

Introduction

The hematopoietic system is one of the most dynamic and stable systems in the organism. Hematopoiesis originates in single, pluripotent, hematopoietic stem cells (HSCs) that are capable of differentiation and self-renewal. The ability of HSCs to differentiate into all eight hematopoietic lineages has been confirmed in previous research [1], but further studies are needed to measure the upper limit of the self-renewal potential of HSCs. Prior research shows that hematopoiesis in mice reconstituted with retrovirally-marked HSC is caused by multiple mainly short-lived clones.  These results were obtained by the analysis of the retroviral insertion sites of individual colonies derived from the spleen colony-forming unit (CFU-S) [2]. Polyclonal hematopoiesis was also observed in other animals [3, 4]. The developmental fate of individual, marked clones was studied during the lifespan of several animals. The results revealed that 1) hematopoiesis is mainly the product of the small clones of hematopoietic cells; 2) the lifespan of the majority of clones is only 1 to 2 months; 3) the clones usually function locally; and 4) the vast majority of the clones replace one another sequentially. Primitive HSCs, capable of producing long-lived clones that exist during the entire lifespan of a mouse (constituting approximately 10% of all clones), were detected by the radiation-marker technique [5]. Such clonal kinetics suggests the exhaustion of hematopoietic clones followed by subsequent recruiting of new clones via proliferation (clonal succession).  This also suggests the ability of the HSCs to proliferate and then return to a quiescent status.

Granulocyte colony-stimulating factor (G-CSF) induces the separation of the HSCs from their stromal niches, resulting in their mobilization into the circulation of the body [6]. Repeated injections of G-CSF may induce the proliferation of clones, leading to increased exhaustion of the hematopoietic system. At the same time, mobilized HSCs that have dissociated with their niche might not return to a quiescent state efficiently. Analysis of the influence of G-CSF on the clonal composition in chimeras could validate the stability of the hematopoietic system after such treatment and clarify the mechanisms of clonal hematopoiesis.

In this study, clonal hematopoiesis was demonstrated by using mice that were reconstituted with bone marrow cells expressing the human adenosine deaminase (hADA) gene while undergoing repeated G-CSF treatment. The dosage of 25 μg/kg is considered insufficient for HSC mobilization in mice [7], although it is approximately five times greater than the dosage used for the mobilization of HSCs in humans [6].

Materials and methods

Mice
Twelve to thirty-week-old male and female CBF1 (C57Bl/6xCBA) F1 mice were used as donors and recipients, respectively. Recipient mice were exposed to 1000 cGy ¹³⁷Cs irradiation divided into two sessions, each exposure three hours apart. Donor mice were injected intravenously with 5-Fluorouracil (5-FU, Sigma, USA, 150 mg/kg body weight) two days before bone marrow (BM) aspiration. For the CFU-S assay [8], irradiated female mice were injected i.v. with 1-3x10⁵ bone marrow cells from reconstituted animals and 10-day-old spleen colonies were isolated for DNA analysis.

Transduction of hematopoietic cells with recombinant virus
Donor bone marrow cells from male mice were pre-stimulated for two days by placing the cells on the irradiated (40 Gy) stroma of three-week-old long-term bone marrow cultures, incubated at 37^oC in Fisher medium (ICN, USA), and supplemented with 20% fetal calf serum (Hyclone, USA). Pre-stimulated bone marrow cells were transferred onto the irradiated (40 Gy) monolayer of PGK-hADA cells that produce a retrovirus containing the human ADA gene [9].  The bone marrow cells were incubated in the full media containing 4 μg/ml polybrene (Sigma, USA) for 48 hours, as described [2]. Immediately after, infected cells were injected into irradiated female recipients (1.2 x 10⁶ cells/mouse) for the long-term reconstitution assay. To determine gene transfer efficiency, a small aliquot of cells was injected for CFU-S assay. Transduction efficiency was 90 % (30 CFU-S were analyzed).

Analysis of the recipient animals
Bone marrow samples were collected under light anesthesia from the femurs of individual reconstituted mice before G-CSF treatment. At the same moment the peripheral blood of each mouse was analyzed. The procedure was carried out monthly, ranging from three to eight months after transplantation [2]. In brief, bone marrow was aspirated repeatedly from the left and the right femurs alternatively by puncturing through the knee joint with a 22-gauge needle. Aliquots of bone marrow from each mouse (1-3 x 10⁵ cells) were injected into seven irradiated female recipients for CFU-S (day 10) analysis and the rest of the bone marrow cells were used for DNA isolation. For identification of CFU-S origin, PCR analysis of Smc gene located both on X and Y chromosomes had been used:
5’- CTGAACTATTTGGATCAGATTGC-3’(exon 3) (sense) and 5’-CACCGACGGTCCTTGCAGAT-3’ (exon 4) (antisense) (Surin V.L., unpublished). By using these primers it is possible to synthesize the  391 bp fragment from the gene copy localized on the Y chromosome, and to synthesize the 429 bp fragment from the gene copy localized on the X chromosome. The difference in the fragment length reflects the difference in the intron length on different chromosomes. Thirty-two cycles of PCR were performed: denaturation 94⁰С – 1 min, annealing 62⁰С – 1 min, synthesis 72⁰С – 2 min. Fragments were analyzed in a 2% agarose gel.

PCR and Southern blot analysis of CFU-S-derived colonies
DNA from total bone marrow and individual spleen colonies was extracted and the PGK-hADA provirus was detected by PCR [2]. DNA samples proven to be positive for hADA underwent the standard Southern blotting technique [10]. The samples were digested with the restriction enzyme EcoRI, then analyzed by electrophoresis using a 1% agarose gel. Subsequently, they were transferred to the Hybond N+ filter and hybridized with an hADA cDNA probe, prepared from a 418 bp fragment of hADA gene amplified by PCR [10]. Digestion with EcoRI permits analysis of individual clones, since only one EcoRI restriction site is present within the vector used. The alignment of bands was based on molecular weight standards (phage λ DNA digested with HindIII).

G-CSF treatment
G-CSF (Neupogen 48 Mio U, F.Hoffmann-La Roche) was dissolved in 0.85% NaCl solution with 0,1% bovine serum albumin (Sigma) and injected subcutaneously according to the dosage of 25 μg/kg in 0.2 ml for 4 days per course. The mice received six courses of G-CSF monthly, starting from three months after reconstitution. The last course was performed eight months after reconstitution.
The scheme of the experiments is represented in Fig. 1.

Statistics

Statistical analysis was done using Student's t-test.

Results and discussion

The number of leukocytes and the proportion of granulocytes in the peripheral blood of the reconstituted mice did not change significantly after repeated G-CSF treatment (Fig. 2 A, B). The fluctuation of leukocytes numbers was due to seasonal variations rather than constrained by G-CSF treatment; the frequency of fluctuations was the same for the animals treated with G-CSF as with the placebo animals. There was no influence of the low dose of G-CSF on the mature blood cells, thus supporting the data obtained from non-irradiated mice [11, 12].

The concentration of CFU-S in the bone marrow of the reconstituted mice did not change after G-CSF treatment (Fig. 3 A). Only once after the second course of G-CSF did the concentration of CFU-S increase in the bone marrow of treated mice. Later on such changes were not observed in the bone marrow of those animals.

Among reconstituted mice, 100% donor chimerism is rare; a partial reversal to the hematopoiesis recipient marrow is usually observed. This occurs because of the survival of the recipients’ HSCs even after high doses of irradiation. The ratio of donor and recipient CFU-S were analyzed in the bone marrow of all experimental animals. The dynamics of the changes in donor CFU-S concentration is shown on Fig. 3 B. The proportion of donor CFU-S varied from month to month from 35 to 88%. In the group of reconstituted mice that were not treated with G-CSF, the proportion of donor CFU-S was significantly higher than in the groups that were treated (71.2±6.9% versus 56.5±5.3%, р<0.05). Such differences could be explained by the dual influence of G-CSF on hematopoiesis in chimeras. G-CSF can activate quiescent recipient HSCs that survived after irradiation. Perhaps without G-CSF stimulation such cells would have entered the cycle much later. The reversion to recipients’ hematopoiesis also increased in the old animals [13]. On the other hand, G-CSF could have induced the donor pre-stimulated early HSCs to proliferate and differentiate, thus exhausting CFU-S with their high proliferative potential.

Significant differences (р<0.05) were observed in the proportion of marked CFU-S in reconstituted mice (Fig. 3 С). The proportion of transdused CFU-S in the G-CSF treated group was lower and more stable than the non-treated ones (20.6±7.1% versus 45.7±6.3%). Cells were marked due to their proliferation at the moment of viral infection so they had divided at least once more than the non–marked ones, thereby diminishing their proportion two-fold. Such precursor cells could be more sensitive to G-CSF treatment and exhausted by differentiation sooner than similar cells in non-treated animals. This data suggest that G-CSF can selectively affect different hematopoietic precursor cells, changing their developmental fate and, as a consequence, inducing significant disturbance in the hematopoietic system.

Analysis of individual clones in untreated and treated animals did not reveal significant differences in their average number (Fig. 4 А). It was shown earlier that the number of clones observed depends on the frequency of analysis and the method of pre-stimulation of HSCs before marking them with the retroviral vector [2, 5, 14]. This work revealed that the clonal composition of hematopoietic tissue is not sensitive to extrinsic factors and probably depends on intrinsic regulation.  The tissue is not connected with local stromal or distantly regulated by hematopoietic growth factors [15]. Thus, the hematopoietic system is one of the most stable systems in the organism and also very well protected from external actions (i.e., bleeding and other stresses).

However, G-CSF treatment affects the size of the clones (measured by the number of colonies representing one clone) and their longevity in the bone marrow. The size of the clones significantly decreased upon treatment, as clones were represented by fewer colonies (Fig. 4 B). The period through which those clones were detected was also noticeably shortened (Fig. 4 C). Relatively long-lived clones (detected for more than 3 months) were not observed after G-CSF treatment. Even relatively low doses of G-CSF treatment led to the disconnection of HSCs with the hematopoietic stroma [16]. It was shown previously that the dissociation of HSCs from the stromal microenvironment resulted in the very rare detection of long-living marked clones that function during the lifespan of the organism. Long-living clones were produced only in experiments not involving bone marrow transplantation – the procedure was based on the dissociation of bone marrow cells toward single-cell suspension [5]. Mobilized HSCs differ from their non-mobilized analogues in the bone marrow. The comparison of the mobilized non-differentiated HSC CD34+Lin- or CD34+CD38- from the peripheral blood, along with the bone marrow of donors in xenogeneic (NOD/SCID mice and sheep, revealed that the ability of the mobilized HSCs to maintain hematopoiesis was worse than that of the HSCs from the bone marrow [17, 18]. The proportion of non-dividing cells is higher in the mobilized population [19], however, it was suggested that only cells after mitosis are able mobilize [20]. Each course of mobilization triggers the divided HSCs to leave the niche thus impairing their proliferative potential and shifting their early stem cells’ status toward more mature progenitors. The proliferative potential of HSCs returning to their niches after rounds of G-CSF injections decreased and, as a consequence, they formed clones of diminished numbers of CFU-S and shortened periods of detection in the bone marrow.

Thus, repeated injections of G-CSF in pharmacological concentrations lead to the destabilization of the hematopoietic system. Long-term consequences of HSCs mobilization by means of G-CSF need to be carefully monitored in donors.

Acknowledgements

This study was supported by grants from the Russian Fund of Fundamental Investigation 07-04-00290-а and President of RF МК-3265.2007.4.

References

1. Dick JE, Magli MC, Huszar D, Phillips RA, and Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985;42:71-79.

2. Drize NJ, Keller JR, and Chertkov JL. Local clonal analysis of the hematopoietic system shows that multiple small short-living clones maintain life-long hematopoiesis in reconstituted mice. Blood. 1996;88:2927-2938.

3. Kuramoto K, Follmann DA, Hematti P, Sellers S, Agricola BA, Metzger ME, Donahue RE, von Kalle C, and Dunbar CE. Effect of chronic cytokine therapy on clonal dynamics in nonhuman primates. Blood. 2004;103:4070-4077.

4. Abkowitz JL, Golinelli D, Harrison DE, and Guttorp P. In vivo kinetics of murine hemopoietic stem cells [In Process Citation]. Blood. 2000;96:3399-3405.

5. Drize NJ., Olshanskaya YV, Gerasimova LP, Manakova TE, Samoylina NL, Todria TV, and Chertkov JL. Lifelong hematopoiesis in both reconstituted and sublethally irradiated mice is provided by multiple sequentially recruited stem cells. Exp Hematol. 2001;29:786-794.

6. Morstyn G, Foote MA, Walker T, and Molineux G. Filgrastim (r-metHuG-CSF) in the 21st century: SD/01. Acta Haematol. 2001;105:151-155.

7. Molineux G, Pojda Z, Hampson IN, Lord, BI, and Dexter TM. Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor. Blood. 1990;76:2153-2158.

8. Till JEMEA. A direct measurement of radiation sencitivity of normal mouse bone marrow. Radiation Research. 1961;14:213-221.

9. Luskey BD, Rosenblatt M, Zsebo K, and Williams DA. Stem cell factor, interleukin-3, and interleukin-6 promote retroviral- mediated gene transfer into murine hematopoietic stem cells. Blood. 1992;80:396-402.

10. Maniatis T, Fritsch EF, and Sambrook J. Molecular Cloning, A Laboratory Manual. Cold Spring Harbor Laboratory). 1982.

11. Drize N, Chertkov J, Samoilina N, and Zander A. Effect of cytokine treatment (granulocyte colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice. Exp Hematol. 1996;24:816-822.

12. Nifontova I, Svinareva D, Chertkov JL, Drize N, and Savchenko V. Late consequence of long-term treatment of mice with G-CSF. Bull Exp Biol Med. 2008;145:568-573.

13. Drize N, Chertkov J, Sadovnikova E, Tiessen S, and Zander A. Long-term maintenance of hematopoiesis in irradiated mice by retrovirally transduced peripheral blood stem cells. Blood. 1997;89:1811-1817.

14. Drize NI and Chertkov IL. Clone-Forming Activity of Embryonal Stem Hemopoietic Cells after Transplantation to Newborn or Adult Sublethally Irradiated Mice. Biull Eksp Biol. Med. 2000;130:110-112.

15. Metcalf D. Lineage commitment and maturation in hematopoietic cells: the case for extrinsic regulation. Blood. 1998;92:345-347.

16. Drize N, Gan O, and Zander A. Effect of recombinant human granulocyte colony-stimulating factor treatment of mice on spleen colony-forming unit number and self-renewal capacity. Exp Hematol. 1993;21:1289-1293.

17. Verfaillie CM. Hematopoietic stem cells for transplantation. Nat Immunol. 2002;3:314-317.

18. Korbling M, Anderlini P, and Hematology TA. Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood. 2001;98:2900-2908.

19. Uchida N, He D, Friera AM, Reitsma M, Sasaki D, Chen B, and Tsukamoto A. The unexpected G0/G1 cell cycle status of mobilized hematopoietic stem cells from peripheral blood. Blood. 1997;89:465-472.

20. Wright DE, Cheshier SH, Wagers AJ, Randall TD, Christensen JL, and Weissman IL. Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle. Blood. 2001;97:2278-2285.

" ["~DETAIL_TEXT"]=> string(24192) "

Introduction

The hematopoietic system is one of the most dynamic and stable systems in the organism. Hematopoiesis originates in single, pluripotent, hematopoietic stem cells (HSCs) that are capable of differentiation and self-renewal. The ability of HSCs to differentiate into all eight hematopoietic lineages has been confirmed in previous research [1], but further studies are needed to measure the upper limit of the self-renewal potential of HSCs. Prior research shows that hematopoiesis in mice reconstituted with retrovirally-marked HSC is caused by multiple mainly short-lived clones.  These results were obtained by the analysis of the retroviral insertion sites of individual colonies derived from the spleen colony-forming unit (CFU-S) [2]. Polyclonal hematopoiesis was also observed in other animals [3, 4]. The developmental fate of individual, marked clones was studied during the lifespan of several animals. The results revealed that 1) hematopoiesis is mainly the product of the small clones of hematopoietic cells; 2) the lifespan of the majority of clones is only 1 to 2 months; 3) the clones usually function locally; and 4) the vast majority of the clones replace one another sequentially. Primitive HSCs, capable of producing long-lived clones that exist during the entire lifespan of a mouse (constituting approximately 10% of all clones), were detected by the radiation-marker technique [5]. Such clonal kinetics suggests the exhaustion of hematopoietic clones followed by subsequent recruiting of new clones via proliferation (clonal succession).  This also suggests the ability of the HSCs to proliferate and then return to a quiescent status.

Granulocyte colony-stimulating factor (G-CSF) induces the separation of the HSCs from their stromal niches, resulting in their mobilization into the circulation of the body [6]. Repeated injections of G-CSF may induce the proliferation of clones, leading to increased exhaustion of the hematopoietic system. At the same time, mobilized HSCs that have dissociated with their niche might not return to a quiescent state efficiently. Analysis of the influence of G-CSF on the clonal composition in chimeras could validate the stability of the hematopoietic system after such treatment and clarify the mechanisms of clonal hematopoiesis.

In this study, clonal hematopoiesis was demonstrated by using mice that were reconstituted with bone marrow cells expressing the human adenosine deaminase (hADA) gene while undergoing repeated G-CSF treatment. The dosage of 25 μg/kg is considered insufficient for HSC mobilization in mice [7], although it is approximately five times greater than the dosage used for the mobilization of HSCs in humans [6].

Materials and methods

Mice
Twelve to thirty-week-old male and female CBF1 (C57Bl/6xCBA) F1 mice were used as donors and recipients, respectively. Recipient mice were exposed to 1000 cGy ¹³⁷Cs irradiation divided into two sessions, each exposure three hours apart. Donor mice were injected intravenously with 5-Fluorouracil (5-FU, Sigma, USA, 150 mg/kg body weight) two days before bone marrow (BM) aspiration. For the CFU-S assay [8], irradiated female mice were injected i.v. with 1-3x10⁵ bone marrow cells from reconstituted animals and 10-day-old spleen colonies were isolated for DNA analysis.

Transduction of hematopoietic cells with recombinant virus
Donor bone marrow cells from male mice were pre-stimulated for two days by placing the cells on the irradiated (40 Gy) stroma of three-week-old long-term bone marrow cultures, incubated at 37^oC in Fisher medium (ICN, USA), and supplemented with 20% fetal calf serum (Hyclone, USA). Pre-stimulated bone marrow cells were transferred onto the irradiated (40 Gy) monolayer of PGK-hADA cells that produce a retrovirus containing the human ADA gene [9].  The bone marrow cells were incubated in the full media containing 4 μg/ml polybrene (Sigma, USA) for 48 hours, as described [2]. Immediately after, infected cells were injected into irradiated female recipients (1.2 x 10⁶ cells/mouse) for the long-term reconstitution assay. To determine gene transfer efficiency, a small aliquot of cells was injected for CFU-S assay. Transduction efficiency was 90 % (30 CFU-S were analyzed).

Analysis of the recipient animals
Bone marrow samples were collected under light anesthesia from the femurs of individual reconstituted mice before G-CSF treatment. At the same moment the peripheral blood of each mouse was analyzed. The procedure was carried out monthly, ranging from three to eight months after transplantation [2]. In brief, bone marrow was aspirated repeatedly from the left and the right femurs alternatively by puncturing through the knee joint with a 22-gauge needle. Aliquots of bone marrow from each mouse (1-3 x 10⁵ cells) were injected into seven irradiated female recipients for CFU-S (day 10) analysis and the rest of the bone marrow cells were used for DNA isolation. For identification of CFU-S origin, PCR analysis of Smc gene located both on X and Y chromosomes had been used:
5’- CTGAACTATTTGGATCAGATTGC-3’(exon 3) (sense) and 5’-CACCGACGGTCCTTGCAGAT-3’ (exon 4) (antisense) (Surin V.L., unpublished). By using these primers it is possible to synthesize the  391 bp fragment from the gene copy localized on the Y chromosome, and to synthesize the 429 bp fragment from the gene copy localized on the X chromosome. The difference in the fragment length reflects the difference in the intron length on different chromosomes. Thirty-two cycles of PCR were performed: denaturation 94⁰С – 1 min, annealing 62⁰С – 1 min, synthesis 72⁰С – 2 min. Fragments were analyzed in a 2% agarose gel.

PCR and Southern blot analysis of CFU-S-derived colonies
DNA from total bone marrow and individual spleen colonies was extracted and the PGK-hADA provirus was detected by PCR [2]. DNA samples proven to be positive for hADA underwent the standard Southern blotting technique [10]. The samples were digested with the restriction enzyme EcoRI, then analyzed by electrophoresis using a 1% agarose gel. Subsequently, they were transferred to the Hybond N+ filter and hybridized with an hADA cDNA probe, prepared from a 418 bp fragment of hADA gene amplified by PCR [10]. Digestion with EcoRI permits analysis of individual clones, since only one EcoRI restriction site is present within the vector used. The alignment of bands was based on molecular weight standards (phage λ DNA digested with HindIII).

G-CSF treatment
G-CSF (Neupogen 48 Mio U, F.Hoffmann-La Roche) was dissolved in 0.85% NaCl solution with 0,1% bovine serum albumin (Sigma) and injected subcutaneously according to the dosage of 25 μg/kg in 0.2 ml for 4 days per course. The mice received six courses of G-CSF monthly, starting from three months after reconstitution. The last course was performed eight months after reconstitution.
The scheme of the experiments is represented in Fig. 1.

Statistics

Statistical analysis was done using Student's t-test.

Results and discussion

The number of leukocytes and the proportion of granulocytes in the peripheral blood of the reconstituted mice did not change significantly after repeated G-CSF treatment (Fig. 2 A, B). The fluctuation of leukocytes numbers was due to seasonal variations rather than constrained by G-CSF treatment; the frequency of fluctuations was the same for the animals treated with G-CSF as with the placebo animals. There was no influence of the low dose of G-CSF on the mature blood cells, thus supporting the data obtained from non-irradiated mice [11, 12].

The concentration of CFU-S in the bone marrow of the reconstituted mice did not change after G-CSF treatment (Fig. 3 A). Only once after the second course of G-CSF did the concentration of CFU-S increase in the bone marrow of treated mice. Later on such changes were not observed in the bone marrow of those animals.

Among reconstituted mice, 100% donor chimerism is rare; a partial reversal to the hematopoiesis recipient marrow is usually observed. This occurs because of the survival of the recipients’ HSCs even after high doses of irradiation. The ratio of donor and recipient CFU-S were analyzed in the bone marrow of all experimental animals. The dynamics of the changes in donor CFU-S concentration is shown on Fig. 3 B. The proportion of donor CFU-S varied from month to month from 35 to 88%. In the group of reconstituted mice that were not treated with G-CSF, the proportion of donor CFU-S was significantly higher than in the groups that were treated (71.2±6.9% versus 56.5±5.3%, р<0.05). Such differences could be explained by the dual influence of G-CSF on hematopoiesis in chimeras. G-CSF can activate quiescent recipient HSCs that survived after irradiation. Perhaps without G-CSF stimulation such cells would have entered the cycle much later. The reversion to recipients’ hematopoiesis also increased in the old animals [13]. On the other hand, G-CSF could have induced the donor pre-stimulated early HSCs to proliferate and differentiate, thus exhausting CFU-S with their high proliferative potential.

Significant differences (р<0.05) were observed in the proportion of marked CFU-S in reconstituted mice (Fig. 3 С). The proportion of transdused CFU-S in the G-CSF treated group was lower and more stable than the non-treated ones (20.6±7.1% versus 45.7±6.3%). Cells were marked due to their proliferation at the moment of viral infection so they had divided at least once more than the non–marked ones, thereby diminishing their proportion two-fold. Such precursor cells could be more sensitive to G-CSF treatment and exhausted by differentiation sooner than similar cells in non-treated animals. This data suggest that G-CSF can selectively affect different hematopoietic precursor cells, changing their developmental fate and, as a consequence, inducing significant disturbance in the hematopoietic system.

Analysis of individual clones in untreated and treated animals did not reveal significant differences in their average number (Fig. 4 А). It was shown earlier that the number of clones observed depends on the frequency of analysis and the method of pre-stimulation of HSCs before marking them with the retroviral vector [2, 5, 14]. This work revealed that the clonal composition of hematopoietic tissue is not sensitive to extrinsic factors and probably depends on intrinsic regulation.  The tissue is not connected with local stromal or distantly regulated by hematopoietic growth factors [15]. Thus, the hematopoietic system is one of the most stable systems in the organism and also very well protected from external actions (i.e., bleeding and other stresses).

However, G-CSF treatment affects the size of the clones (measured by the number of colonies representing one clone) and their longevity in the bone marrow. The size of the clones significantly decreased upon treatment, as clones were represented by fewer colonies (Fig. 4 B). The period through which those clones were detected was also noticeably shortened (Fig. 4 C). Relatively long-lived clones (detected for more than 3 months) were not observed after G-CSF treatment. Even relatively low doses of G-CSF treatment led to the disconnection of HSCs with the hematopoietic stroma [16]. It was shown previously that the dissociation of HSCs from the stromal microenvironment resulted in the very rare detection of long-living marked clones that function during the lifespan of the organism. Long-living clones were produced only in experiments not involving bone marrow transplantation – the procedure was based on the dissociation of bone marrow cells toward single-cell suspension [5]. Mobilized HSCs differ from their non-mobilized analogues in the bone marrow. The comparison of the mobilized non-differentiated HSC CD34+Lin- or CD34+CD38- from the peripheral blood, along with the bone marrow of donors in xenogeneic (NOD/SCID mice and sheep, revealed that the ability of the mobilized HSCs to maintain hematopoiesis was worse than that of the HSCs from the bone marrow [17, 18]. The proportion of non-dividing cells is higher in the mobilized population [19], however, it was suggested that only cells after mitosis are able mobilize [20]. Each course of mobilization triggers the divided HSCs to leave the niche thus impairing their proliferative potential and shifting their early stem cells’ status toward more mature progenitors. The proliferative potential of HSCs returning to their niches after rounds of G-CSF injections decreased and, as a consequence, they formed clones of diminished numbers of CFU-S and shortened periods of detection in the bone marrow.

Thus, repeated injections of G-CSF in pharmacological concentrations lead to the destabilization of the hematopoietic system. Long-term consequences of HSCs mobilization by means of G-CSF need to be carefully monitored in donors.

Acknowledgements

This study was supported by grants from the Russian Fund of Fundamental Investigation 07-04-00290-а and President of RF МК-3265.2007.4.

References

1. Dick JE, Magli MC, Huszar D, Phillips RA, and Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985;42:71-79.

2. Drize NJ, Keller JR, and Chertkov JL. Local clonal analysis of the hematopoietic system shows that multiple small short-living clones maintain life-long hematopoiesis in reconstituted mice. Blood. 1996;88:2927-2938.

3. Kuramoto K, Follmann DA, Hematti P, Sellers S, Agricola BA, Metzger ME, Donahue RE, von Kalle C, and Dunbar CE. Effect of chronic cytokine therapy on clonal dynamics in nonhuman primates. Blood. 2004;103:4070-4077.

4. Abkowitz JL, Golinelli D, Harrison DE, and Guttorp P. In vivo kinetics of murine hemopoietic stem cells [In Process Citation]. Blood. 2000;96:3399-3405.

5. Drize NJ., Olshanskaya YV, Gerasimova LP, Manakova TE, Samoylina NL, Todria TV, and Chertkov JL. Lifelong hematopoiesis in both reconstituted and sublethally irradiated mice is provided by multiple sequentially recruited stem cells. Exp Hematol. 2001;29:786-794.

6. Morstyn G, Foote MA, Walker T, and Molineux G. Filgrastim (r-metHuG-CSF) in the 21st century: SD/01. Acta Haematol. 2001;105:151-155.

7. Molineux G, Pojda Z, Hampson IN, Lord, BI, and Dexter TM. Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor. Blood. 1990;76:2153-2158.

8. Till JEMEA. A direct measurement of radiation sencitivity of normal mouse bone marrow. Radiation Research. 1961;14:213-221.

9. Luskey BD, Rosenblatt M, Zsebo K, and Williams DA. Stem cell factor, interleukin-3, and interleukin-6 promote retroviral- mediated gene transfer into murine hematopoietic stem cells. Blood. 1992;80:396-402.

10. Maniatis T, Fritsch EF, and Sambrook J. Molecular Cloning, A Laboratory Manual. Cold Spring Harbor Laboratory). 1982.

11. Drize N, Chertkov J, Samoilina N, and Zander A. Effect of cytokine treatment (granulocyte colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice. Exp Hematol. 1996;24:816-822.

12. Nifontova I, Svinareva D, Chertkov JL, Drize N, and Savchenko V. Late consequence of long-term treatment of mice with G-CSF. Bull Exp Biol Med. 2008;145:568-573.

13. Drize N, Chertkov J, Sadovnikova E, Tiessen S, and Zander A. Long-term maintenance of hematopoiesis in irradiated mice by retrovirally transduced peripheral blood stem cells. Blood. 1997;89:1811-1817.

14. Drize NI and Chertkov IL. Clone-Forming Activity of Embryonal Stem Hemopoietic Cells after Transplantation to Newborn or Adult Sublethally Irradiated Mice. Biull Eksp Biol. Med. 2000;130:110-112.

15. Metcalf D. Lineage commitment and maturation in hematopoietic cells: the case for extrinsic regulation. Blood. 1998;92:345-347.

16. Drize N, Gan O, and Zander A. Effect of recombinant human granulocyte colony-stimulating factor treatment of mice on spleen colony-forming unit number and self-renewal capacity. Exp Hematol. 1993;21:1289-1293.

17. Verfaillie CM. Hematopoietic stem cells for transplantation. Nat Immunol. 2002;3:314-317.

18. Korbling M, Anderlini P, and Hematology TA. Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood. 2001;98:2900-2908.

19. Uchida N, He D, Friera AM, Reitsma M, Sasaki D, Chen B, and Tsukamoto A. The unexpected G0/G1 cell cycle status of mobilized hematopoietic stem cells from peripheral blood. Blood. 1997;89:465-472.

20. Wright DE, Cheshier SH, Wagers AJ, Randall TD, Christensen JL, and Weissman IL. Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle. Blood. 2001;97:2278-2285.

" ["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(83) "vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer" ["~CODE"]=> string(83) "vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer" ["EXTERNAL_ID"]=> string(3) "866" ["~EXTERNAL_ID"]=> string(3) "866" ["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(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["ELEMENT_META_KEYWORDS"]=> string(212) "гемопоэтические стволовые клетки колониеобразующая селезеночная единица (КОЕ-с) ретровирусный перенос генов Г-КСФ" ["ELEMENT_META_DESCRIPTION"]=> string(253) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химерClonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(4613) "<h3>Введение</h3> <p>Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).</p> <h3>Материалы и методы</h3> <p> В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену <em>smc</em>, сцепленному с полом, или по маркеру <em>hADA</em>, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода.  <br /></p> <h3>Результаты</h3> <p>Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р&lt;0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ. <br /></p><h3>Заключение</h3> <p>Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.</p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_META_TITLE"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_META_KEYWORDS"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_META_DESCRIPTION"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_PICTURE_FILE_ALT"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_PICTURE_FILE_TITLE"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_PICTURE_FILE_NAME"]=> string(87) "vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer-img" ["SECTION_DETAIL_PICTURE_FILE_ALT"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_DETAIL_PICTURE_FILE_TITLE"]=> string(153) "Влияние длительного введения Г-КСФ на клональный состав кроветворной ткани у химер" ["SECTION_DETAIL_PICTURE_FILE_NAME"]=> string(87) "vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer-img" ["ELEMENT_PREVIEW_PICTURE_FILE_NAME"]=> string(87) "vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer-img" ["ELEMENT_DETAIL_PICTURE_FILE_NAME"]=> string(87) "vliyanie-dlitelnogo-vvedeniya-g-ksf-na-klonalnyy-sostav-krovetvornoy-tkani-u-khimer-img" } ["FIELDS"]=> array(1) { ["IBLOCK_SECTION_ID"]=> string(2) "34" } ["PROPERTIES"]=> array(18) { ["KEYWORDS"]=> array(36) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(4) { [0]=> string(5) "11904" [1]=> string(5) "11905" [2]=> string(5) "11906" [3]=> string(5) "11907" } ["VALUE"]=> array(4) { [0]=> string(3) "686" [1]=> string(3) "863" [2]=> string(3) "864" [3]=> string(3) "865" } ["DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(4) { [0]=> string(3) "686" [1]=> string(3) "863" [2]=> string(3) "864" [3]=> string(3) "865" } ["~DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11825" ["VALUE"]=> string(22) "10/10/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "10/10/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11826" ["VALUE"]=> string(22) "11/13/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/13/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11827" ["VALUE"]=> string(22) "12/10/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/10/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL } ["CONTACT"]=> array(36) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11828" ["VALUE"]=> string(3) "833" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "833" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(6) { [0]=> string(5) "11908" [1]=> string(5) "11909" [2]=> string(5) "11910" [3]=> string(5) "11911" [4]=> string(5) "11912" [5]=> string(5) "11913" } ["VALUE"]=> array(6) { [0]=> string(3) "830" [1]=> string(3) "860" [2]=> string(3) "831" [3]=> string(3) "861" [4]=> string(3) "833" [5]=> string(3) "862" } ["DESCRIPTION"]=> array(6) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(6) { [0]=> string(3) "830" [1]=> string(3) "860" [2]=> string(3) "831" [3]=> string(3) "861" [4]=> string(3) "833" [5]=> string(3) "862" } ["~DESCRIPTION"]=> array(6) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "11847" ["VALUE"]=> array(2) { ["TEXT"]=> string(202) "<p class="Autor">Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(180) "

Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.

" ["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) "11848" ["VALUE"]=> array(2) { ["TEXT"]=> string(4613) "<h3>Введение</h3> <p>Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).</p> <h3>Материалы и методы</h3> <p> В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену <em>smc</em>, сцепленному с полом, или по маркеру <em>hADA</em>, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода.  <br /></p> <h3>Результаты</h3> <p>Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р&lt;0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ. <br /></p><h3>Заключение</h3> <p>Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(4477) "

Введение

Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).

Материалы и методы

В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену smc, сцепленному с полом, или по маркеру hADA, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода. 

Результаты

Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р<0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ.

Заключение

Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11835" ["VALUE"]=> string(30) "10.3205/ctt-2008-en-000017.01 " ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(30) "10.3205/ctt-2008-en-000017.01 " ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "11871" ["VALUE"]=> array(2) { ["TEXT"]=> string(150) "<p class="Autor">Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(128) "

Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "11872" ["VALUE"]=> array(2) { ["TEXT"]=> string(106) "<p>National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(94) "

National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia

" ["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) "11873" ["VALUE"]=> array(2) { ["TEXT"]=> string(702) "<p class="bodytext">The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses<br> of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(674) "

The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses
of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11836" ["VALUE"]=> string(100) "Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(100) "Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_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) "42" ["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(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11849" ["VALUE"]=> string(3) "509" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "509" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11850" ["VALUE"]=> string(3) "510" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "510" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["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) "45" ["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(80) } ["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(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(13) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "11871" ["VALUE"]=> array(2) { ["TEXT"]=> string(150) "<p class="Autor">Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(128) "

Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(128) "

Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko

" } ["SUMMARY_EN"]=> array(37) { ["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) "11873" ["VALUE"]=> array(2) { ["TEXT"]=> string(702) "<p class="bodytext">The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses<br> of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(674) "

The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses
of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system.

" ["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(674) "

The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses
of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11835" ["VALUE"]=> string(30) "10.3205/ctt-2008-en-000017.01 " ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(30) "10.3205/ctt-2008-en-000017.01 " ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(30) "10.3205/ctt-2008-en-000017.01 " } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11836" ["VALUE"]=> string(100) "Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(100) "Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(100) "Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "11872" ["VALUE"]=> array(2) { ["TEXT"]=> string(106) "<p>National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(94) "

National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(94) "

National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia

" } ["AUTHORS"]=> array(38) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(6) { [0]=> string(5) "11908" [1]=> string(5) "11909" [2]=> string(5) "11910" [3]=> string(5) "11911" [4]=> string(5) "11912" [5]=> string(5) "11913" } ["VALUE"]=> array(6) { [0]=> string(3) "830" [1]=> string(3) "860" [2]=> string(3) "831" [3]=> string(3) "861" [4]=> string(3) "833" [5]=> string(3) "862" } ["DESCRIPTION"]=> array(6) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(6) { [0]=> string(3) "830" [1]=> string(3) "860" [2]=> string(3) "831" [3]=> string(3) "861" [4]=> string(3) "833" [5]=> string(3) "862" } ["~DESCRIPTION"]=> array(6) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(6) { [0]=> string(71) "Irina Shipounova (Nifontova)" [1]=> string(55) "Natalia Sats" [2]=> string(58) "Daria Svinareva" [3]=> string(58) "Tatiana Petrova" [4]=> string(53) "Nina Drize" [5]=> string(60) "Valeriy Savchenko" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "11847" ["VALUE"]=> array(2) { ["TEXT"]=> string(202) "<p class="Autor">Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(180) "

Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(180) "

Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.

" } ["SUBMITTED"]=> array(37) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11825" ["VALUE"]=> string(22) "10/10/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "10/10/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "10/10/2008 12:00:00 am" } ["ACCEPTED"]=> array(37) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11826" ["VALUE"]=> string(22) "11/13/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/13/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "11/13/2008 12:00:00 am" } ["PUBLISHED"]=> array(37) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11827" ["VALUE"]=> string(22) "12/10/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/10/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "12/10/2008 12:00:00 am" } ["KEYWORDS"]=> array(38) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(4) { [0]=> string(5) "11904" [1]=> string(5) "11905" [2]=> string(5) "11906" [3]=> string(5) "11907" } ["VALUE"]=> array(4) { [0]=> string(3) "686" [1]=> string(3) "863" [2]=> string(3) "864" [3]=> string(3) "865" } ["DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(4) { [0]=> string(3) "686" [1]=> string(3) "863" [2]=> string(3) "864" [3]=> string(3) "865" } ["~DESCRIPTION"]=> array(4) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(4) { [0]=> string(106) "гемопоэтические стволовые клетки" [1]=> string(130) "колониеобразующая селезеночная единица (КОЕ-с)" [2]=> string(96) "ретровирусный перенос генов" [3]=> string(53) "Г-КСФ" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["CONTACT"]=> array(38) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11828" ["VALUE"]=> string(3) "833" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "833" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(53) "Nina Drize" ["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) "11848" ["VALUE"]=> array(2) { ["TEXT"]=> string(4613) "<h3>Введение</h3> <p>Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).</p> <h3>Материалы и методы</h3> <p> В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену <em>smc</em>, сцепленному с полом, или по маркеру <em>hADA</em>, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода.  <br /></p> <h3>Результаты</h3> <p>Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р&lt;0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ. <br /></p><h3>Заключение</h3> <p>Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(4477) "

Введение

Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).

Материалы и методы

В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену smc, сцепленному с полом, или по маркеру hADA, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода. 

Результаты

Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р<0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ.

Заключение

Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.

" ["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(4477) "

Введение

Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).

Материалы и методы

В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену smc, сцепленному с полом, или по маркеру hADA, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода. 

Результаты

Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р<0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ.

Заключение

Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.

" } } } [3]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "34" ["~IBLOCK_SECTION_ID"]=> string(2) "34" ["ID"]=> string(3) "881" ["~ID"]=> string(3) "881" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["~NAME"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "06/15/2017 01:24:13 pm" ["~TIMESTAMP_X"]=> string(22) "06/15/2017 01:24:13 pm" ["DETAIL_PAGE_URL"]=> string(128) "/en/archive/Volume-1/stati/kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii/" ["~DETAIL_PAGE_URL"]=> string(128) "/en/archive/Volume-1/stati/kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(31982) "

Introduction

Fungal infections with Aspergillus or Candida, mainly of the lung, are a major cause of treatment-related mortality in allogeneic stem cell transplantation (SCT) [1, 2]. Invasive Aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients was associated with case-fatality rates of 87% [3], and an overall 1-year survival rate of only 20% [4]. Patients with a history of systemic or invasive fungal infection (IFI) who undergo allogeneic transplantation are considered to be at high risk of disease reactivation or progression leading to a high mortality. More recently, leukemias and other malignancies have been treated with more intensive induction therapies up front, resulting in a higher incidence of fungal infections before receiving a stem cell transplant. 

Primary antifungal prophylaxis is given routinely in patients with no prior IFI who undergo allogeneic stem cell transplantation [5-9], whereas secondary prophylaxis is given in patients with prior IFI. Up to now, for those patients with a history of IFI who undergo allogeneic SCT, no prospective study of secondary antifungal prophylaxis in a larger series of these high-risk patients exists. More recently, several retrospective studies indicate that bone marrow transplantation (BMT) in patients with a history of IA is feasible [10-12]. Apart from that, the only case reports that can be found in the literature concern patients with fungal disease who underwent SCT and were successfully treated with fluconazole, itraconazole, surgical resection, amphotericin B, and voriconazole [13-15].

We therefore conducted a prospective single-center study to evaluate the efficacy and safety of caspofungin as secondary prophylaxis or therapy, in order to prevent recurrence or progression of systemic or invasive fungal infections in patients with a history of IFI who underwent allogeneic SCT. 
Caspofungin is an echinocandin, which interferes with fungal cell wall assembly by inhibition of  β(1,3)-D-glucan synthase, an enzyme not present in mammalian cells [16]. It shows no signs of nephrotoxicity and has only modest side effects, such as chills and fever, in very few patients (1-3 %). Caspofungin has proven to be effective and well-tolerated in the treatment of infections caused by Aspergillus and Candida species in clinical trials [17-24].

Patients and methods

Study design
Patients included in our study had a history of proven or probable IFI according to modified EORTC criteria for diagnosis of invasive fungal infection. Proven IFI requires histo- or cytopathology positive for hyphae with evidence of associated tissue damage or a positive culture for mold species from a normally sterile site consistent with infection. Probable IFI included cases with one host criterion plus one microbial criterion and one major or two minor clinical criteria, or a patient with recent neutropenia or an allogeneic SCT patient with a chest CT scan positive for "halo" or "air crescent" signs [25-28]. The patients included were scheduled to undergo an allogeneic bone marrow or stem cell transplantation and needed to have sufficient organ function.

The primary efficacy endpoint was the incidence of clinically manifest mycoses under the prophylactic use of caspofungin (development of breakthrough IFI) or response thereof, in case of florid infections at start of conditioning. The secondary endpoints were the evaluation of toxicity and overall survival until day +365. Failure was defined as suspected or documented fungal infection (failure to prevent a new IFI), or a progressive fungal infection in case of prior florid activity (failure to improve a partially treated IFI). Secondary endpoints were evaluated descriptively. All patients included were evaluated on an intent-to-treat basis.

Modified EORTC criteria for diagnosis of IFI are more clinically oriented than the strict EORTC-IFICG/MSG criteria (European Organization for Research and Treatment of Cancer - IFI Cooperative Group & Mycoses Study Group). These criteria were specifically developed for use in large clinical trials on the efficacy of antifungals and should not be used to guide clinical decisions [25]. This approach is reflected by the clinical practice in BMT, where proven and even probable IFI with direct microbiological evidence are diagnosed in only a minority of high risk patients, and diagnosis of fungal infection is often made on clinical and radiological grounds alone.

Prior to study entry, we performed a chest CT scan, a bronchoalveolar lavage (BAL), and an abdominal ultrasound. We also carried out a high-resolution chest CT scan at the end of the caspofungin prophylaxis or in case of fever. Weekly controls of circulating Aspergillus galactomannan antigen (Platelia^® Aspergillus EIA, index used for cut-off was 1.0, BioRad Laboratories, Hercules, CA, USA) and Candida antibody titer (Cand-Tec^® latex agglutination test for heat-labile antigen, Ramco Laboratories, Stafford, TX, USA) were performed in all patients. To measure potential side effects we conducted daily blood counts and clinical chemistry analyses.

Patients
Successive patients with a history of systemic or invasive fungal infection in the past who underwent allogeneic BMT were included in this prospective study. 
Conditioning was performed with myeloablative regimens. In unrelated donors and mismatched family donors, we added anti-thymocyte globulin (ATG Fresenius, 30-90 mg/kg intravenously (i.v.)) to the conditioning in order to minimize the risk of graft-versus-host disease (GvHD). Cyclosporin A (CSA) for immunosuppression was given to all patients post-transplant with a target level of 200-300 µg/L. The local ethics committee approved the study and all patients gave prior written informed consent.

Treatment plan & response assessment
Patients were given 50 mg caspofungin i.v. daily over one hour, following a 70 mg loading dose from start of conditioning until stable engraftment. No other systemic antifungal was given. All patients were nursed in reversed isolation in conventional or laminar airflow rooms. Antibiotic prophylaxis consisted of ciprofloxacin, local antifungals, and acyclovir. Prophylaxis against pneumocystis carinii was carried out with cotrimoxazole (or pentamidine inhalation). CMV-negative patients received only CMV-negative blood products. All blood products were irradiated at 25 Gy. CMV-positive patients were monitored weekly for CMV infection by PCR and/or antigenemia-assay for pp65. Preemptive therapy was started with 10 mg/kg gancyclovir after two consecutive positive PCR or one positive antigenemia-assay. In the case of neutropenic fever during transplantation, ceftazidime and vancomycin were given; if fever or signs of infection persisted, tobramycin was added after two days. In patients without signs of fungal infection after engraftment, antimycotic prophylaxis was switched to itraconazole 200 mg twice daily until day +100.An experienced clinician and radiologist performed the mycological response assessment according to EORTC criteria. Radiographic criteria for complete response (CR) required a > 90% clearing of CT scan abnormalities associated with active fungal infection or persistent residual scarring only. Partial response (PR) required a > 50% improvement in radiographic abnormalities on relevant scans, as compared to baseline. Stable response was diagnosed if minor or no improvement occurred and there was no worsening of attributable radiographic signs of the IFI. Failure included worsening CT scan abnormalities consistent with progressive infection or, clinically, an increase in the number and/or severity of clinical signs and symptoms attributable to the IFI.

Results

Patients' characteristics
Twenty-eight successive patients from one center, all of whom happened to have acute leukemias, were included in this prospective study from July 2001 to September 2003 (details of patients are given in Table 1). Patients included in this study had a history of probable (n=26) or proven (n=2) systemic or invasive fungal infection in the past according to modified EORTC criteria, which include typical signs of fungal infection on a CT scan closely related to neutropenia. 
Prior fungal infection was diagnosed by a CT scan of the lungs (n=27) and liver, spleen or kidneys (n=9) at a median of 3 months before transplant (range 1 week – 3 years).

Table 1. Patients' characteristics

At the beginning of transplantation, 12 patients (often unexpectedly) had florid infections by CT scan criteria, 10 had residuals and 6 were in CR. A bronchoscopy (BAL) and an abdominal ultrasound were performed prior to conditioning in most patients, but were not as informative as high resolution CT scans. However, in two patients with residual disease, we isolated Candida albicans via BAL in one, and Candida glabrata in the other.

Conditioning was performed with myeloablative regimens. Median duration of neutropenia was 18 days (range 7-47). Transplants were from unrelated (n=19) and related (n=9) donors, 6 of whom had a mismatch.

Side effects and toxicity of caspofungin
Caspofungin was given over a median duration of 27 days (range 15-47), which was similar in patients with and without active signs of IFI at the start of caspofungin. It was not necessary to discontinue caspofungin due to side effects in any patient. Median toxicity of conditioning, immunosuppression and supportive therapy according to Bearman was comparable to historic controls: mouth: grade 2, liver: grade 1, kidney: grade 0, and gut: grade 0. Maximal laboratory values (median and range) for liver and renal toxicity during caspofungin prophylaxis or therapy were: total bilirubin 2.7 mg/dL (range 1.2-22.2, normal ≤ 1.0), AST 36 U/L (range 6-215, normal ≤ 18), ALT 46 U/L (range 9-299, normal ≤ 22), and creatinine 1.1 mg/dL (range 0.7-3.0, normal ≤ 1.2). When maximal bilirubin was > 6 (n=4) mg/dL it was either due to liver toxicity (n=3), not related to any particular drug, or suspected hepatic veno-occlusive disease (n=1). When maximal creatinine was > 2 mg/dL (n=6) it was usually due to the nephrotoxic side effects of antibiotics given for fever and CSA. It is noteworthy that caspofungin was well tolerated in all 28 patients who received CSA for immunosuppression post-transplant without any associated renal or hepatic problems. No CSA dosage adaptation was required due to liver toxicity potentially related to caspofungin. Ten out of 28 patients experienced acute GvHD ≥ grade 2 after engraftment and prior to day +100 and needed additional immunosuppression.

Response to caspofungin
Importantly, in 10 out of 12 cases (83%) a florid fungal infection with a positive CT scan at start of transplantation responded to caspofungin alone, with 4 CR and 6 PR despite severe immunosuppression (Table 2).

Two case reports are shown for illustration (Figure 1). Four out of 12 patients received additional granulocyte transfusions during aplasia, and one patient with prolonged aplasia of 29 days nevertheless developed a fungal infection. In 14 out of 16 patients (88 %) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. Only 2 out of 16 patients developed a fungal infection under caspofungin despite additional granulocyte transfusions. Both patients had prolonged aplasia for 40 and 47 days, respectively.

Figure 1. Case reports of responses to caspofungin. Shown are chest CT scans of patients undergoing stem cell transplantation prior conditioning and after engraftment.

Treatment failure was defined as documented or suspected progressive fungal infection.

In 4 out of 28 patients (1 CR, 1 residual and 2 florid states prior to transplantation) anti-mycotic treatment was, therefore, changed from caspofungin to second-line agents such as voriconazole, amphotericin B or AmBisome^® i.v. (= 14% failure rate). Three out of four patients who developed a fungal infection following HSCT despite prophylaxis or therapy with caspofungin had delayed engraftment or primary graft failure with 29, 40 and 47 days of aplasia with leucocytes <1000 /µl.

The four patients who failed on caspofungin had suspected or documented progressive fungal infection until engraftment. All four had a positive chest CT scan with worsening of radiographic signs and only one had positive antigen tests for IFI. Patient 1 had increasing CRP, a positive test for Aspergillus antigen, and 40 days of aplasia due to primary graft failure. She received granulocytes and her autologous backup, responded to voriconazole and amphotericin B (PR), but still had residuals at day +100 and developed new infiltrates later. Patient 2 was BAL negative. She responded to voriconazole initially (PR) but died before day +100 from alveolar hemorrhage with pancytopenia and suspected fungal pneumonia. Patient 3 had a fever, Aspergillus fumigatus in BAL, and a normal antifungal serology (failure of secondary prophylaxis with fungal breakthrough infection). He had 47 days of aplasia, received granulocytes, and had grade 2 toxicity of mouth, liver, and kidney. He was treated with amphotericin B and had a CR from his fungal disease by day +100. However, he later died from a relapse of his leukemia. Patient 4 had 29 days of aplasia. She was given AmBisome^®, responded with a CR, but died of multi-organ failure prior to day +100.

One patient with florid nodular infiltrates responded to caspofungin initially (PR), but received high dose steroids because of severe acute skin GvHD after engraftment, and later died of systemic Scedosporium prolificans resistant to caspofungin.

1 Year outcome
Overall mortality at one year was as high as expected. 11 out of 28 patients (39%) had died with overall survival of 61%. Causes of death were: pneumonia with sepsis (n=3) with suspected fungal pneumonia in two cases, systemic fungal sepsis with Scedosporium (n=1), sepsis of unknown etiology (n=1), alveolar hemorrhage (n=1), multi-organ failure (n=2), and relapse of leukemia (n=3). Five deaths were associated with pancytopenia or secondary graft failure and five fatalities with severe GvHD. Transplant-related mortality (TRM) was 8 out of 28 patients (29%) and no death was attributed to caspofungin. Six out of 8 patients who died due to TRM within the first year had signs of pulmonary infiltrates at time of death, and in 2 cases these were indicative of active IFI (patients A and B, see below). Only 1 out of 17 patients still alive at 1 year had signs of residual fungal disease (patient C, see below).

Relapse IFI of the lung in the first year post transplant after the initial phase of caspofungin prophylaxis or therapy was suspected in 3 patients (patients who had a relapse of their leukemia prior to developing signs of IFI are not included): At 1.5 months after transplant, patient A, after being treated with steroids for skin and gut GvHD, still under itraconazole prophylaxis, developed atypical infiltrates on chest CT scan. He was treated with antibiotics and voriconazole, and died of pneumonia shortly thereafter. Eight months after transplant, patient B, after a cholecystitis and colitis, showed a positive chest X-ray and voriconazole treatment was initiated; he developed an ileus and died shortly thereafter of multi-organ failure. After 8 and 10 months, patient C (caspofungin-failure patient 1), after a relapse of her leukemia and another SCT with primary graft failure, developed new round infiltrates on chest CT scan, which regressed under therapy with voriconazole.

Six out of 28 patients (21%) experienced a relapse of their leukemia in the first year after transplant. Three patients underwent a second SCT and achieved a complete remission of their leukemia. One patient progressed despite reinduction therapy and two patients received palliative therapy only. At one year, all 17 patients alive were in complete remission with regard to their underlying disease.

Discussion

This is the first prospective, non-controlled, single-center study of secondary antifungal prophylaxis or therapy in allogeneic SCT in high-risk patients with prior systemic or invasive fungal infections. Caspofungin is effective for secondary prophylaxis and in those patients with an active infection at time of SCT. In 88% of patients (n=16) without active signs of infection at start of transplantation, secondary prophylaxis with caspofungin was successful, and in 83% of patients (n=12), a florid fungal infection at the time of transplantation responded to caspofungin despite aplasia and additional immunosuppression. Scheduled transplantations were not delayed until fungal infections resolved, for this may have had major implications for prognosis.

Six patients received 1 to 6 granulocyte transfusions (median 3) before engraftment, which could also attribute to the resolution of fungal infection. Three patients failed on caspofungin despite receiving granulocytes. Each of these patients had prolonged aplasia >4 weeks (one had signs of florid infection, one had residuals, and one was in CR at the start of transplantation).

Retrospective studies had indicated that BMT in patients with a history of IA is feasible. Offner et al. performed a multicenter retrospective analysis of 48 patients with documented or probable IA prior to BMT using various antifungals for secondary prophylaxis. The overall incidence of relapse IA was lower than expected (33%), but the mortality rate among relapsed patients was 88% [10]. Fukuda et al. described a 10-year experience at a single transplant center and included 45 patients with a known history of IA before HSCT. Post-transplantation IA occurred in 13 of these patients, 9 infections were considered recurrent. Compared with other patients who received allogeneic HSCT during the same period, patients with histories of IA had a lower overall survival of 56% and a higher TRM of 38% at 100 days after BMT [11].

Post-transplantation IA occurred more frequently in patients who received < 1 month of antifungal therapy prior to BMT. Patients receiving >1 month of antifungal therapy and who had a resolution of radiographic abnormalities did better. Recently, Cordonnier et al. have shown that voriconazole may be useful to prevent reactivation of prior fungal disease in a retrospective study of 9 patients undergoing allogeneic HSCT [12]. These included 5 proven and 4 probable cases of IA according to EORTC criteria and at time of transplant, 3 patients had residual fungal disease. Voriconazole 400 mg/day i.v. or p.o. was given from start of conditioning until end of immunosuppression. None of the patients experienced fungal relapse or new fungal disease and scheduled treatment was not delayed. Voriconazole was well tolerated, except in one patient who had abnormal liver tests secondary to GvHD, and one who had transient visual disturbances.

Caspofungin was chosen in our prospective study as secondary prophylaxis or therapy because of its high efficacy in Aspergillus and Candida infections and its low side effects [22]. Caspofungin is active in vitro against Candida spp., including C. krusei, C. glabrata and C. tropicalis, as well as Aspergillus spp., such as A. fumigatus, A. flavus and A. niger. Caspofungin is resistant, however, against Fusarium, Rhizopus, Cryptococcus and Scedosporium prolificans [22]. Caspofungin has shown high efficacy in clinical trials in esophageal candidiasis, refractory invasive aspergillosis, candidemia, and empiric antifungal therapy. It has been approved for first-line therapy of candidemia and second-line therapy of aspergillosis [17-23].

Sable et al. analyzed the safety and tolerability of caspofungin, which was generally well tolerated; caspofungin was discontinued only in 2% of patients due to adverse events [24]. Drug-related adverse events were fever, local phlebitis at the infusion-site, headache and nausea. Renal tolerability was excellent and transient mild-to-moderate elevations in ALT, AST and alkaline phosphatase levels were observed. In our study, caspofungin was well tolerated and did not have to be discontinued due to side effects in a single patient. It is of note that caspofungin was safe in all 28 patients who received cyclosporin A (CSA) for immunosuppression post-transplant without any liver or renal problems due to CSA. Similar results have been found by Sanz-Rodriguez et al. recently in 13 patients who received CSA concomitantly [29]. The incidence of liver and renal toxicity and acute GvHD ≥ grade 2 was comparable to historic controls without caspofungin.

Long-term aplasia is a high risk factor for fungal (breakthrough) infection. Chest CT scans prior to transplantation and frequently thereafter, e.g. once weekly, are likely to benefit this high-risk group of patients. In our study, in 12 out of 28 cases chest CT scans revealed a florid infection at start of transplantation despite a lack of clinical signs and symptoms.

A limitation of our study was that no control group existed; therefore conclusions about toxicity and efficacy are based on clinical experience and should be handled with caution. There also was a tendency to declare failure in neutropenic patients who had increasing infiltrates on CT scan, and to discontinue caspofungin early despite the lack of concrete evidence of IFI (this was possibly relevant in 3 out of 4 patients).

In conclusion, the use of caspofungin as secondary prophylaxis or therapy in high-risk patients with a history or persistence of IFI undergoing allogeneic SCT is safe and effective. It does not result in a high toxicity and shows a low incidence of breakthrough infections. This allows SCT to proceed as scheduled, even if signs of florid fungal disease are still evident at time of transplant.

Acknowledgements

We thank the staff of the BMT unit for providing excellent care of our patients, the radiologists for their cooperation, and the medical technicians for their excellent work in the BMT laboratory.

References

1. Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, et al. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood. 2003;102(3):827-833.

2. Wingard JR. Antifungal chemoprophylaxis after blood and marrow transplantation. Clin Infect Dis. 2002;34(10):1386-1390.

3. Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32(3):358-366.

4. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34(7):909-917.

5. Hamza NS, Ghannoum MA, Lazarus HM. Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2004;34(5):377-389.

6. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326(13):845-851.

7. Slavin MA, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation - a prospective, randomized, double-blind study. J Infect Dis. 1995;171(6):1545-1552.

8. Marr KA, Seidel K, Slavin MA, Bowden RA, Schoch HG, Flowers ME, et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood. 2000;96(6):2055-2061.

9. Dykewicz CA. Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2001;33(2):139-144.

10. Offner F, Cordonnier C, Ljungman P, Prentice HG, Engelhard D, De Bacquer D, et al. Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis. 1998;26(5):1098-1103.

11. Fukuda T, Boeckh M, Guthrie KA, Mattson DK, Owens S, Wald A, et al. Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center. Biol Blood Marrow Transplant. 2004;10(7):494-503.

12. Cordonnier C, Maury S, Pautas C, Bastie JN, Chehata S, Castaigne S, et al. Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients. Bone Marrow Transplant. 2004;33(9):943-948.

13. Martino R, Nomdedeu J, Altes A, Sureda A, Brunet S, Martinez C, et al. Successful bone marrow transplantation in patients with previous invasive fungal infections: report of four cases. Bone Marrow Transplant. 1994;13(3):265-269.

14. Richard C, Romon I, Baro J, Insunza A, Loyola I, Zurbano F, et al. Invasive pulmonary aspergillosis prior to BMT in acute leukemia patients does not predict a poor outcome. Bone Marrow Transplant. 1993;12(3):237-241.

15. Mattei D, Mordini N, Lo NC, Ghirardo D, Ferrua MT, Osenda M, et al. Voriconazole in the management of invasive aspergillosis in two patients with acute myeloid leukemia undergoing stem cell transplantation. Bone Marrow Transplant. 2002;30(12):967-970.

16. Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362(9390):1142-1151.

17. Villanueva A, Arathoon EG, Gotuzzo E, Berman RS, DiNubile MJ, Sable CA. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 2001;33(9):1529-1535.

18. Villanueva A, Gotuzzo E, Arathoon EG, Noriega LM, Kartsonis NA, Lupinacci RJ, et al. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med. 2002;113(4):294-299.

19. Arathoon EG, Gotuzzo E, Noriega LM, Berman RS, DiNubile MJ, Sable CA. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother. 2002;46(2):451-457.

20. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020-2029.

21. Maertens J, Boogaerts M. Caspofungin in the treatment of candidosis and aspergillosis. Int J Infect Dis. 2003;7(2):94-101.

22. Letscher-Bru V, Herbrecht R. Caspofungin: the first representative of a new antifungal class. J Antimicrob Chemother. 2003;51(3):513-521.

23. Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351(14):1391-1402.

24. Sable CA, Nguyen BY, Chodakewitz JA, DiNubile MJ. Safety and tolerability of caspofungin acetate in the treatment of fungal infections. Transpl Infect Dis. 2002;4(1):25-30.

25. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34(1):7-14.

26. Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol. 2001;19(1):253-259.

27. Kuhlman JE, Fishman EK, Burch PA, Karp JE, Zerhouni EA, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management. Chest. 1987;92(1):95-99.

28. Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology. 1985;157(3):611-614.

29. Sanz-Rodriguez C, Lopez-Duarte M, Jurado M, Lopez J, Arranz R, Cisneros JM, et al. Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections. Bone Marrow Transplant. 2004.

" ["~DETAIL_TEXT"]=> string(31982) "

Introduction

Fungal infections with Aspergillus or Candida, mainly of the lung, are a major cause of treatment-related mortality in allogeneic stem cell transplantation (SCT) [1, 2]. Invasive Aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients was associated with case-fatality rates of 87% [3], and an overall 1-year survival rate of only 20% [4]. Patients with a history of systemic or invasive fungal infection (IFI) who undergo allogeneic transplantation are considered to be at high risk of disease reactivation or progression leading to a high mortality. More recently, leukemias and other malignancies have been treated with more intensive induction therapies up front, resulting in a higher incidence of fungal infections before receiving a stem cell transplant. 

Primary antifungal prophylaxis is given routinely in patients with no prior IFI who undergo allogeneic stem cell transplantation [5-9], whereas secondary prophylaxis is given in patients with prior IFI. Up to now, for those patients with a history of IFI who undergo allogeneic SCT, no prospective study of secondary antifungal prophylaxis in a larger series of these high-risk patients exists. More recently, several retrospective studies indicate that bone marrow transplantation (BMT) in patients with a history of IA is feasible [10-12]. Apart from that, the only case reports that can be found in the literature concern patients with fungal disease who underwent SCT and were successfully treated with fluconazole, itraconazole, surgical resection, amphotericin B, and voriconazole [13-15].

We therefore conducted a prospective single-center study to evaluate the efficacy and safety of caspofungin as secondary prophylaxis or therapy, in order to prevent recurrence or progression of systemic or invasive fungal infections in patients with a history of IFI who underwent allogeneic SCT. 
Caspofungin is an echinocandin, which interferes with fungal cell wall assembly by inhibition of  β(1,3)-D-glucan synthase, an enzyme not present in mammalian cells [16]. It shows no signs of nephrotoxicity and has only modest side effects, such as chills and fever, in very few patients (1-3 %). Caspofungin has proven to be effective and well-tolerated in the treatment of infections caused by Aspergillus and Candida species in clinical trials [17-24].

Patients and methods

Study design
Patients included in our study had a history of proven or probable IFI according to modified EORTC criteria for diagnosis of invasive fungal infection. Proven IFI requires histo- or cytopathology positive for hyphae with evidence of associated tissue damage or a positive culture for mold species from a normally sterile site consistent with infection. Probable IFI included cases with one host criterion plus one microbial criterion and one major or two minor clinical criteria, or a patient with recent neutropenia or an allogeneic SCT patient with a chest CT scan positive for "halo" or "air crescent" signs [25-28]. The patients included were scheduled to undergo an allogeneic bone marrow or stem cell transplantation and needed to have sufficient organ function.

The primary efficacy endpoint was the incidence of clinically manifest mycoses under the prophylactic use of caspofungin (development of breakthrough IFI) or response thereof, in case of florid infections at start of conditioning. The secondary endpoints were the evaluation of toxicity and overall survival until day +365. Failure was defined as suspected or documented fungal infection (failure to prevent a new IFI), or a progressive fungal infection in case of prior florid activity (failure to improve a partially treated IFI). Secondary endpoints were evaluated descriptively. All patients included were evaluated on an intent-to-treat basis.

Modified EORTC criteria for diagnosis of IFI are more clinically oriented than the strict EORTC-IFICG/MSG criteria (European Organization for Research and Treatment of Cancer - IFI Cooperative Group & Mycoses Study Group). These criteria were specifically developed for use in large clinical trials on the efficacy of antifungals and should not be used to guide clinical decisions [25]. This approach is reflected by the clinical practice in BMT, where proven and even probable IFI with direct microbiological evidence are diagnosed in only a minority of high risk patients, and diagnosis of fungal infection is often made on clinical and radiological grounds alone.

Prior to study entry, we performed a chest CT scan, a bronchoalveolar lavage (BAL), and an abdominal ultrasound. We also carried out a high-resolution chest CT scan at the end of the caspofungin prophylaxis or in case of fever. Weekly controls of circulating Aspergillus galactomannan antigen (Platelia^® Aspergillus EIA, index used for cut-off was 1.0, BioRad Laboratories, Hercules, CA, USA) and Candida antibody titer (Cand-Tec^® latex agglutination test for heat-labile antigen, Ramco Laboratories, Stafford, TX, USA) were performed in all patients. To measure potential side effects we conducted daily blood counts and clinical chemistry analyses.

Patients
Successive patients with a history of systemic or invasive fungal infection in the past who underwent allogeneic BMT were included in this prospective study. 
Conditioning was performed with myeloablative regimens. In unrelated donors and mismatched family donors, we added anti-thymocyte globulin (ATG Fresenius, 30-90 mg/kg intravenously (i.v.)) to the conditioning in order to minimize the risk of graft-versus-host disease (GvHD). Cyclosporin A (CSA) for immunosuppression was given to all patients post-transplant with a target level of 200-300 µg/L. The local ethics committee approved the study and all patients gave prior written informed consent.

Treatment plan & response assessment
Patients were given 50 mg caspofungin i.v. daily over one hour, following a 70 mg loading dose from start of conditioning until stable engraftment. No other systemic antifungal was given. All patients were nursed in reversed isolation in conventional or laminar airflow rooms. Antibiotic prophylaxis consisted of ciprofloxacin, local antifungals, and acyclovir. Prophylaxis against pneumocystis carinii was carried out with cotrimoxazole (or pentamidine inhalation). CMV-negative patients received only CMV-negative blood products. All blood products were irradiated at 25 Gy. CMV-positive patients were monitored weekly for CMV infection by PCR and/or antigenemia-assay for pp65. Preemptive therapy was started with 10 mg/kg gancyclovir after two consecutive positive PCR or one positive antigenemia-assay. In the case of neutropenic fever during transplantation, ceftazidime and vancomycin were given; if fever or signs of infection persisted, tobramycin was added after two days. In patients without signs of fungal infection after engraftment, antimycotic prophylaxis was switched to itraconazole 200 mg twice daily until day +100.An experienced clinician and radiologist performed the mycological response assessment according to EORTC criteria. Radiographic criteria for complete response (CR) required a > 90% clearing of CT scan abnormalities associated with active fungal infection or persistent residual scarring only. Partial response (PR) required a > 50% improvement in radiographic abnormalities on relevant scans, as compared to baseline. Stable response was diagnosed if minor or no improvement occurred and there was no worsening of attributable radiographic signs of the IFI. Failure included worsening CT scan abnormalities consistent with progressive infection or, clinically, an increase in the number and/or severity of clinical signs and symptoms attributable to the IFI.

Results

Patients' characteristics
Twenty-eight successive patients from one center, all of whom happened to have acute leukemias, were included in this prospective study from July 2001 to September 2003 (details of patients are given in Table 1). Patients included in this study had a history of probable (n=26) or proven (n=2) systemic or invasive fungal infection in the past according to modified EORTC criteria, which include typical signs of fungal infection on a CT scan closely related to neutropenia. 
Prior fungal infection was diagnosed by a CT scan of the lungs (n=27) and liver, spleen or kidneys (n=9) at a median of 3 months before transplant (range 1 week – 3 years).

Table 1. Patients' characteristics

At the beginning of transplantation, 12 patients (often unexpectedly) had florid infections by CT scan criteria, 10 had residuals and 6 were in CR. A bronchoscopy (BAL) and an abdominal ultrasound were performed prior to conditioning in most patients, but were not as informative as high resolution CT scans. However, in two patients with residual disease, we isolated Candida albicans via BAL in one, and Candida glabrata in the other.

Conditioning was performed with myeloablative regimens. Median duration of neutropenia was 18 days (range 7-47). Transplants were from unrelated (n=19) and related (n=9) donors, 6 of whom had a mismatch.

Side effects and toxicity of caspofungin
Caspofungin was given over a median duration of 27 days (range 15-47), which was similar in patients with and without active signs of IFI at the start of caspofungin. It was not necessary to discontinue caspofungin due to side effects in any patient. Median toxicity of conditioning, immunosuppression and supportive therapy according to Bearman was comparable to historic controls: mouth: grade 2, liver: grade 1, kidney: grade 0, and gut: grade 0. Maximal laboratory values (median and range) for liver and renal toxicity during caspofungin prophylaxis or therapy were: total bilirubin 2.7 mg/dL (range 1.2-22.2, normal ≤ 1.0), AST 36 U/L (range 6-215, normal ≤ 18), ALT 46 U/L (range 9-299, normal ≤ 22), and creatinine 1.1 mg/dL (range 0.7-3.0, normal ≤ 1.2). When maximal bilirubin was > 6 (n=4) mg/dL it was either due to liver toxicity (n=3), not related to any particular drug, or suspected hepatic veno-occlusive disease (n=1). When maximal creatinine was > 2 mg/dL (n=6) it was usually due to the nephrotoxic side effects of antibiotics given for fever and CSA. It is noteworthy that caspofungin was well tolerated in all 28 patients who received CSA for immunosuppression post-transplant without any associated renal or hepatic problems. No CSA dosage adaptation was required due to liver toxicity potentially related to caspofungin. Ten out of 28 patients experienced acute GvHD ≥ grade 2 after engraftment and prior to day +100 and needed additional immunosuppression.

Response to caspofungin
Importantly, in 10 out of 12 cases (83%) a florid fungal infection with a positive CT scan at start of transplantation responded to caspofungin alone, with 4 CR and 6 PR despite severe immunosuppression (Table 2).

Two case reports are shown for illustration (Figure 1). Four out of 12 patients received additional granulocyte transfusions during aplasia, and one patient with prolonged aplasia of 29 days nevertheless developed a fungal infection. In 14 out of 16 patients (88 %) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. Only 2 out of 16 patients developed a fungal infection under caspofungin despite additional granulocyte transfusions. Both patients had prolonged aplasia for 40 and 47 days, respectively.

Figure 1. Case reports of responses to caspofungin. Shown are chest CT scans of patients undergoing stem cell transplantation prior conditioning and after engraftment.

Treatment failure was defined as documented or suspected progressive fungal infection.

In 4 out of 28 patients (1 CR, 1 residual and 2 florid states prior to transplantation) anti-mycotic treatment was, therefore, changed from caspofungin to second-line agents such as voriconazole, amphotericin B or AmBisome^® i.v. (= 14% failure rate). Three out of four patients who developed a fungal infection following HSCT despite prophylaxis or therapy with caspofungin had delayed engraftment or primary graft failure with 29, 40 and 47 days of aplasia with leucocytes <1000 /µl.

The four patients who failed on caspofungin had suspected or documented progressive fungal infection until engraftment. All four had a positive chest CT scan with worsening of radiographic signs and only one had positive antigen tests for IFI. Patient 1 had increasing CRP, a positive test for Aspergillus antigen, and 40 days of aplasia due to primary graft failure. She received granulocytes and her autologous backup, responded to voriconazole and amphotericin B (PR), but still had residuals at day +100 and developed new infiltrates later. Patient 2 was BAL negative. She responded to voriconazole initially (PR) but died before day +100 from alveolar hemorrhage with pancytopenia and suspected fungal pneumonia. Patient 3 had a fever, Aspergillus fumigatus in BAL, and a normal antifungal serology (failure of secondary prophylaxis with fungal breakthrough infection). He had 47 days of aplasia, received granulocytes, and had grade 2 toxicity of mouth, liver, and kidney. He was treated with amphotericin B and had a CR from his fungal disease by day +100. However, he later died from a relapse of his leukemia. Patient 4 had 29 days of aplasia. She was given AmBisome^®, responded with a CR, but died of multi-organ failure prior to day +100.

One patient with florid nodular infiltrates responded to caspofungin initially (PR), but received high dose steroids because of severe acute skin GvHD after engraftment, and later died of systemic Scedosporium prolificans resistant to caspofungin.

1 Year outcome
Overall mortality at one year was as high as expected. 11 out of 28 patients (39%) had died with overall survival of 61%. Causes of death were: pneumonia with sepsis (n=3) with suspected fungal pneumonia in two cases, systemic fungal sepsis with Scedosporium (n=1), sepsis of unknown etiology (n=1), alveolar hemorrhage (n=1), multi-organ failure (n=2), and relapse of leukemia (n=3). Five deaths were associated with pancytopenia or secondary graft failure and five fatalities with severe GvHD. Transplant-related mortality (TRM) was 8 out of 28 patients (29%) and no death was attributed to caspofungin. Six out of 8 patients who died due to TRM within the first year had signs of pulmonary infiltrates at time of death, and in 2 cases these were indicative of active IFI (patients A and B, see below). Only 1 out of 17 patients still alive at 1 year had signs of residual fungal disease (patient C, see below).

Relapse IFI of the lung in the first year post transplant after the initial phase of caspofungin prophylaxis or therapy was suspected in 3 patients (patients who had a relapse of their leukemia prior to developing signs of IFI are not included): At 1.5 months after transplant, patient A, after being treated with steroids for skin and gut GvHD, still under itraconazole prophylaxis, developed atypical infiltrates on chest CT scan. He was treated with antibiotics and voriconazole, and died of pneumonia shortly thereafter. Eight months after transplant, patient B, after a cholecystitis and colitis, showed a positive chest X-ray and voriconazole treatment was initiated; he developed an ileus and died shortly thereafter of multi-organ failure. After 8 and 10 months, patient C (caspofungin-failure patient 1), after a relapse of her leukemia and another SCT with primary graft failure, developed new round infiltrates on chest CT scan, which regressed under therapy with voriconazole.

Six out of 28 patients (21%) experienced a relapse of their leukemia in the first year after transplant. Three patients underwent a second SCT and achieved a complete remission of their leukemia. One patient progressed despite reinduction therapy and two patients received palliative therapy only. At one year, all 17 patients alive were in complete remission with regard to their underlying disease.

Discussion

This is the first prospective, non-controlled, single-center study of secondary antifungal prophylaxis or therapy in allogeneic SCT in high-risk patients with prior systemic or invasive fungal infections. Caspofungin is effective for secondary prophylaxis and in those patients with an active infection at time of SCT. In 88% of patients (n=16) without active signs of infection at start of transplantation, secondary prophylaxis with caspofungin was successful, and in 83% of patients (n=12), a florid fungal infection at the time of transplantation responded to caspofungin despite aplasia and additional immunosuppression. Scheduled transplantations were not delayed until fungal infections resolved, for this may have had major implications for prognosis.

Six patients received 1 to 6 granulocyte transfusions (median 3) before engraftment, which could also attribute to the resolution of fungal infection. Three patients failed on caspofungin despite receiving granulocytes. Each of these patients had prolonged aplasia >4 weeks (one had signs of florid infection, one had residuals, and one was in CR at the start of transplantation).

Retrospective studies had indicated that BMT in patients with a history of IA is feasible. Offner et al. performed a multicenter retrospective analysis of 48 patients with documented or probable IA prior to BMT using various antifungals for secondary prophylaxis. The overall incidence of relapse IA was lower than expected (33%), but the mortality rate among relapsed patients was 88% [10]. Fukuda et al. described a 10-year experience at a single transplant center and included 45 patients with a known history of IA before HSCT. Post-transplantation IA occurred in 13 of these patients, 9 infections were considered recurrent. Compared with other patients who received allogeneic HSCT during the same period, patients with histories of IA had a lower overall survival of 56% and a higher TRM of 38% at 100 days after BMT [11].

Post-transplantation IA occurred more frequently in patients who received < 1 month of antifungal therapy prior to BMT. Patients receiving >1 month of antifungal therapy and who had a resolution of radiographic abnormalities did better. Recently, Cordonnier et al. have shown that voriconazole may be useful to prevent reactivation of prior fungal disease in a retrospective study of 9 patients undergoing allogeneic HSCT [12]. These included 5 proven and 4 probable cases of IA according to EORTC criteria and at time of transplant, 3 patients had residual fungal disease. Voriconazole 400 mg/day i.v. or p.o. was given from start of conditioning until end of immunosuppression. None of the patients experienced fungal relapse or new fungal disease and scheduled treatment was not delayed. Voriconazole was well tolerated, except in one patient who had abnormal liver tests secondary to GvHD, and one who had transient visual disturbances.

Caspofungin was chosen in our prospective study as secondary prophylaxis or therapy because of its high efficacy in Aspergillus and Candida infections and its low side effects [22]. Caspofungin is active in vitro against Candida spp., including C. krusei, C. glabrata and C. tropicalis, as well as Aspergillus spp., such as A. fumigatus, A. flavus and A. niger. Caspofungin is resistant, however, against Fusarium, Rhizopus, Cryptococcus and Scedosporium prolificans [22]. Caspofungin has shown high efficacy in clinical trials in esophageal candidiasis, refractory invasive aspergillosis, candidemia, and empiric antifungal therapy. It has been approved for first-line therapy of candidemia and second-line therapy of aspergillosis [17-23].

Sable et al. analyzed the safety and tolerability of caspofungin, which was generally well tolerated; caspofungin was discontinued only in 2% of patients due to adverse events [24]. Drug-related adverse events were fever, local phlebitis at the infusion-site, headache and nausea. Renal tolerability was excellent and transient mild-to-moderate elevations in ALT, AST and alkaline phosphatase levels were observed. In our study, caspofungin was well tolerated and did not have to be discontinued due to side effects in a single patient. It is of note that caspofungin was safe in all 28 patients who received cyclosporin A (CSA) for immunosuppression post-transplant without any liver or renal problems due to CSA. Similar results have been found by Sanz-Rodriguez et al. recently in 13 patients who received CSA concomitantly [29]. The incidence of liver and renal toxicity and acute GvHD ≥ grade 2 was comparable to historic controls without caspofungin.

Long-term aplasia is a high risk factor for fungal (breakthrough) infection. Chest CT scans prior to transplantation and frequently thereafter, e.g. once weekly, are likely to benefit this high-risk group of patients. In our study, in 12 out of 28 cases chest CT scans revealed a florid infection at start of transplantation despite a lack of clinical signs and symptoms.

A limitation of our study was that no control group existed; therefore conclusions about toxicity and efficacy are based on clinical experience and should be handled with caution. There also was a tendency to declare failure in neutropenic patients who had increasing infiltrates on CT scan, and to discontinue caspofungin early despite the lack of concrete evidence of IFI (this was possibly relevant in 3 out of 4 patients).

In conclusion, the use of caspofungin as secondary prophylaxis or therapy in high-risk patients with a history or persistence of IFI undergoing allogeneic SCT is safe and effective. It does not result in a high toxicity and shows a low incidence of breakthrough infections. This allows SCT to proceed as scheduled, even if signs of florid fungal disease are still evident at time of transplant.

Acknowledgements

We thank the staff of the BMT unit for providing excellent care of our patients, the radiologists for their cooperation, and the medical technicians for their excellent work in the BMT laboratory.

References

1. Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, et al. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood. 2003;102(3):827-833.

2. Wingard JR. Antifungal chemoprophylaxis after blood and marrow transplantation. Clin Infect Dis. 2002;34(10):1386-1390.

3. Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32(3):358-366.

4. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34(7):909-917.

5. Hamza NS, Ghannoum MA, Lazarus HM. Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2004;34(5):377-389.

6. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326(13):845-851.

7. Slavin MA, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation - a prospective, randomized, double-blind study. J Infect Dis. 1995;171(6):1545-1552.

8. Marr KA, Seidel K, Slavin MA, Bowden RA, Schoch HG, Flowers ME, et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood. 2000;96(6):2055-2061.

9. Dykewicz CA. Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2001;33(2):139-144.

10. Offner F, Cordonnier C, Ljungman P, Prentice HG, Engelhard D, De Bacquer D, et al. Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis. 1998;26(5):1098-1103.

11. Fukuda T, Boeckh M, Guthrie KA, Mattson DK, Owens S, Wald A, et al. Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center. Biol Blood Marrow Transplant. 2004;10(7):494-503.

12. Cordonnier C, Maury S, Pautas C, Bastie JN, Chehata S, Castaigne S, et al. Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients. Bone Marrow Transplant. 2004;33(9):943-948.

13. Martino R, Nomdedeu J, Altes A, Sureda A, Brunet S, Martinez C, et al. Successful bone marrow transplantation in patients with previous invasive fungal infections: report of four cases. Bone Marrow Transplant. 1994;13(3):265-269.

14. Richard C, Romon I, Baro J, Insunza A, Loyola I, Zurbano F, et al. Invasive pulmonary aspergillosis prior to BMT in acute leukemia patients does not predict a poor outcome. Bone Marrow Transplant. 1993;12(3):237-241.

15. Mattei D, Mordini N, Lo NC, Ghirardo D, Ferrua MT, Osenda M, et al. Voriconazole in the management of invasive aspergillosis in two patients with acute myeloid leukemia undergoing stem cell transplantation. Bone Marrow Transplant. 2002;30(12):967-970.

16. Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362(9390):1142-1151.

17. Villanueva A, Arathoon EG, Gotuzzo E, Berman RS, DiNubile MJ, Sable CA. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 2001;33(9):1529-1535.

18. Villanueva A, Gotuzzo E, Arathoon EG, Noriega LM, Kartsonis NA, Lupinacci RJ, et al. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med. 2002;113(4):294-299.

19. Arathoon EG, Gotuzzo E, Noriega LM, Berman RS, DiNubile MJ, Sable CA. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother. 2002;46(2):451-457.

20. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020-2029.

21. Maertens J, Boogaerts M. Caspofungin in the treatment of candidosis and aspergillosis. Int J Infect Dis. 2003;7(2):94-101.

22. Letscher-Bru V, Herbrecht R. Caspofungin: the first representative of a new antifungal class. J Antimicrob Chemother. 2003;51(3):513-521.

23. Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351(14):1391-1402.

24. Sable CA, Nguyen BY, Chodakewitz JA, DiNubile MJ. Safety and tolerability of caspofungin acetate in the treatment of fungal infections. Transpl Infect Dis. 2002;4(1):25-30.

25. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34(1):7-14.

26. Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol. 2001;19(1):253-259.

27. Kuhlman JE, Fishman EK, Burch PA, Karp JE, Zerhouni EA, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management. Chest. 1987;92(1):95-99.

28. Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology. 1985;157(3):611-614.

29. Sanz-Rodriguez C, Lopez-Duarte M, Jurado M, Lopez J, Arranz R, Cisneros JM, et al. Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections. Bone Marrow Transplant. 2004.

" ["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) "kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii" ["~CODE"]=> string(100) "kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii" ["EXTERNAL_ID"]=> string(3) "881" ["~EXTERNAL_ID"]=> string(3) "881" ["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(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["ELEMENT_META_KEYWORDS"]=> string(241) "аллогенная трансплантация стволовых клеток инвазивные грибковые инфекции (ИГИ) профилактика инфекционные осложнения каспофунгин" ["ELEMENT_META_DESCRIPTION"]=> string(521) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекцийCaspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(3471) "<h3>Состояние вопроса</h3> <p> Грибковые инфекции, вызванные <em>Aspergillus</em> or <em>Candida</em>, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы. </p> <h3>Методы</h3> <p>Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана <em>Aspergillus</em> и антител к <em>Candida</em> проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата. </p> <h3>Результаты</h3> <p>Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином. </p> <h3>Выводы</h3> <p>Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.</p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_META_TITLE"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_META_KEYWORDS"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_META_DESCRIPTION"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_PICTURE_FILE_ALT"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_PICTURE_FILE_TITLE"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_PICTURE_FILE_NAME"]=> string(100) "kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii" ["SECTION_DETAIL_PICTURE_FILE_ALT"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_DETAIL_PICTURE_FILE_TITLE"]=> string(340) "Каспофунгин в качестве вторичной профилактики или терапии у больных при аллогенной трансплантации стволовых клеток с предыдущей историей или риском системных или инвазивных инфекций" ["SECTION_DETAIL_PICTURE_FILE_NAME"]=> string(100) "kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii" ["ELEMENT_PREVIEW_PICTURE_FILE_NAME"]=> string(100) "kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii" ["ELEMENT_DETAIL_PICTURE_FILE_NAME"]=> string(100) "kaspofungin-v-kachestve-vtorichnoy-profilaktiki-ili-terapii-u-bolnykh-pri-allogennoy-transplantatsii" } ["FIELDS"]=> array(1) { ["IBLOCK_SECTION_ID"]=> string(2) "34" } ["PROPERTIES"]=> array(18) { ["KEYWORDS"]=> array(36) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(5) { [0]=> string(5) "12220" [1]=> string(5) "12221" [2]=> string(5) "12222" [3]=> string(5) "12223" [4]=> string(5) "12224" } ["VALUE"]=> array(5) { [0]=> string(3) "625" [1]=> string(3) "878" [2]=> string(3) "287" [3]=> string(3) "879" [4]=> string(3) "880" } ["DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(5) { [0]=> string(3) "625" [1]=> string(3) "878" [2]=> string(3) "287" [3]=> string(3) "879" [4]=> string(3) "880" } ["~DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11984" ["VALUE"]=> string(22) "10/17/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "10/17/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11985" ["VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11986" ["VALUE"]=> string(22) "11/28/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/28/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL } ["CONTACT"]=> array(36) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11987" ["VALUE"]=> string(3) "707" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "707" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(14) { [0]=> string(5) "12225" [1]=> string(5) "12226" [2]=> string(5) "12227" [3]=> string(5) "12228" [4]=> string(5) "12229" [5]=> string(5) "12230" [6]=> string(5) "12231" [7]=> string(5) "12232" [8]=> string(5) "12233" [9]=> string(5) "12234" [10]=> string(5) "12235" [11]=> string(5) "12236" [12]=> string(5) "12237" [13]=> string(5) "12238" } ["VALUE"]=> array(14) { [0]=> string(3) "867" [1]=> string(3) "868" [2]=> string(2) "41" [3]=> string(3) "869" [4]=> string(3) "870" [5]=> string(3) "871" [6]=> string(3) "872" [7]=> string(3) "873" [8]=> string(3) "874" [9]=> string(3) "875" [10]=> string(3) "876" [11]=> string(3) "877" [12]=> string(2) "11" [13]=> string(3) "707" } ["DESCRIPTION"]=> array(14) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" [6]=> string(0) "" [7]=> string(0) "" [8]=> string(0) "" [9]=> string(0) "" [10]=> string(0) "" [11]=> string(0) "" [12]=> string(0) "" [13]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(14) { [0]=> string(3) "867" [1]=> string(3) "868" [2]=> string(2) "41" [3]=> string(3) "869" [4]=> string(3) "870" [5]=> string(3) "871" [6]=> string(3) "872" [7]=> string(3) "873" [8]=> string(3) "874" [9]=> string(3) "875" [10]=> string(3) "876" [11]=> string(3) "877" [12]=> string(2) "11" [13]=> string(3) "707" } ["~DESCRIPTION"]=> array(14) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" [6]=> string(0) "" [7]=> string(0) "" [8]=> string(0) "" [9]=> string(0) "" [10]=> string(0) "" [11]=> string(0) "" [12]=> string(0) "" [13]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "12002" ["VALUE"]=> array(2) { ["TEXT"]=> string(329) "<p class="Autor">Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,<br> фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(301) "

Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,
фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.

" ["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) "12003" ["VALUE"]=> array(2) { ["TEXT"]=> string(3471) "<h3>Состояние вопроса</h3> <p> Грибковые инфекции, вызванные <em>Aspergillus</em> or <em>Candida</em>, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы. </p> <h3>Методы</h3> <p>Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана <em>Aspergillus</em> и антител к <em>Candida</em> проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата. </p> <h3>Результаты</h3> <p>Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином. </p> <h3>Выводы</h3> <p>Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3327) "

Состояние вопроса

Грибковые инфекции, вызванные Aspergillus or Candida, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы.

Методы

Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана Aspergillus и антител к Candida проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата.

Результаты

Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином.

Выводы

Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "12004" ["VALUE"]=> string(29) "10.3205/ctt-2008-en-000021.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2008-en-000021.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "12046" ["VALUE"]=> array(2) { ["TEXT"]=> string(218) "<p class="Autor">N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(196) "

N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "12047" ["VALUE"]=> array(2) { ["TEXT"]=> string(684) "<p class="bodytext">Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany </p> <br> <p class="bodytext"><b>Correspondence:</b><br> Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.rovsikivDyoi2yrm1leqfyvk2hi');" class="mail">nkroeger@<span style="display:none;">spam is bad</span>uke.uni-hamburg.de</a> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(562) "

Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany

Correspondence:
Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: nkroeger@spam is baduke.uni-hamburg.de

" ["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) "12048" ["VALUE"]=> array(2) { ["TEXT"]=> string(1424) "<h3>Background</h3> <p>Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.</p> <h3>Methods</h3> <p>Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. </p> <h3>Results</h3> <p>No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. </p><h3>Conclusions</h3> <p>The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.</p> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1322) "

Background

Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.

Methods

Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. 

Results

No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. 

Conclusions

The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "12005" ["VALUE"]=> string(181) "Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(181) "Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_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) "42" ["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(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "12025" ["VALUE"]=> string(3) "521" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "521" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "12026" ["VALUE"]=> string(3) "522" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "522" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["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) "45" ["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(80) } ["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(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(13) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "37" ["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) "12046" ["VALUE"]=> array(2) { ["TEXT"]=> string(218) "<p class="Autor">N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(196) "

N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(196) "

N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger

" } ["SUMMARY_EN"]=> array(37) { ["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) "12048" ["VALUE"]=> array(2) { ["TEXT"]=> string(1424) "<h3>Background</h3> <p>Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.</p> <h3>Methods</h3> <p>Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. </p> <h3>Results</h3> <p>No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. </p><h3>Conclusions</h3> <p>The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.</p> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1322) "

Background

Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.

Methods

Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. 

Results

No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. 

Conclusions

The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.

" ["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(1322) "

Background

Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.

Methods

Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. 

Results

No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. 

Conclusions

The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["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"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "12004" ["VALUE"]=> string(29) "10.3205/ctt-2008-en-000021.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2008-en-000021.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(29) "10.3205/ctt-2008-en-000021.01" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["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) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "12005" ["VALUE"]=> string(181) "Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(181) "Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(181) "Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_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) "38" ["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) "12047" ["VALUE"]=> array(2) { ["TEXT"]=> string(684) "<p class="bodytext">Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany </p> <br> <p class="bodytext"><b>Correspondence:</b><br> Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.rovsikivDyoi2yrm1leqfyvk2hi');" class="mail">nkroeger@<span style="display:none;">spam is bad</span>uke.uni-hamburg.de</a> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(562) "

Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany

Correspondence:
Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: nkroeger@spam is baduke.uni-hamburg.de

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(562) "

Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany

Correspondence:
Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: nkroeger@spam is baduke.uni-hamburg.de

" } ["AUTHORS"]=> array(38) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(14) { [0]=> string(5) "12225" [1]=> string(5) "12226" [2]=> string(5) "12227" [3]=> string(5) "12228" [4]=> string(5) "12229" [5]=> string(5) "12230" [6]=> string(5) "12231" [7]=> string(5) "12232" [8]=> string(5) "12233" [9]=> string(5) "12234" [10]=> string(5) "12235" [11]=> string(5) "12236" [12]=> string(5) "12237" [13]=> string(5) "12238" } ["VALUE"]=> array(14) { [0]=> string(3) "867" [1]=> string(3) "868" [2]=> string(2) "41" [3]=> string(3) "869" [4]=> string(3) "870" [5]=> string(3) "871" [6]=> string(3) "872" [7]=> string(3) "873" [8]=> string(3) "874" [9]=> string(3) "875" [10]=> string(3) "876" [11]=> string(3) "877" [12]=> string(2) "11" [13]=> string(3) "707" } ["DESCRIPTION"]=> array(14) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" [6]=> string(0) "" [7]=> string(0) "" [8]=> string(0) "" [9]=> string(0) "" [10]=> string(0) "" [11]=> string(0) "" [12]=> string(0) "" [13]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(14) { [0]=> string(3) "867" [1]=> string(3) "868" [2]=> string(2) "41" [3]=> string(3) "869" [4]=> string(3) "870" [5]=> string(3) "871" [6]=> string(3) "872" [7]=> string(3) "873" [8]=> string(3) "874" [9]=> string(3) "875" [10]=> string(3) "876" [11]=> string(3) "877" [12]=> string(2) "11" [13]=> string(3) "707" } ["~DESCRIPTION"]=> array(14) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" [6]=> string(0) "" [7]=> string(0) "" [8]=> string(0) "" [9]=> string(0) "" [10]=> string(0) "" [11]=> string(0) "" [12]=> string(0) "" [13]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(14) { [0]=> string(51) "N. Stute" [1]=> string(54) "T. Zabelina" [2]=> string(53) "Boris Fehse" [3]=> string(57) "W. Hassenpflug" [4]=> string(51) "J. Panse" [5]=> string(54) "C. Wolschke" [6]=> string(50) "F. Ayuk" [7]=> string(54) "H. Schieder" [8]=> string(52) "H. Renges" [9]=> string(58) "A. Kratochwille" [10]=> string(58) "R. von Hinüber" [11]=> string(54) "R. Erttmann" [12]=> string(56) "Axel R. Zander" [13]=> string(59) "Nicolaus Kröger" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_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) "25" ["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) "12002" ["VALUE"]=> array(2) { ["TEXT"]=> string(329) "<p class="Autor">Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,<br> фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(301) "

Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,
фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(301) "

Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,
фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.

" } ["SUBMITTED"]=> array(37) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["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) "20" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11984" ["VALUE"]=> string(22) "10/17/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "10/17/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "10/17/2008 12:00:00 am" } ["ACCEPTED"]=> array(37) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["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) "21" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11985" ["VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/21/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "11/21/2008 12:00:00 am" } ["PUBLISHED"]=> array(37) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["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) "22" ["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(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11986" ["VALUE"]=> string(22) "11/28/2008 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "11/28/2008 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "11/28/2008 12:00:00 am" } ["KEYWORDS"]=> array(38) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(5) { [0]=> string(5) "12220" [1]=> string(5) "12221" [2]=> string(5) "12222" [3]=> string(5) "12223" [4]=> string(5) "12224" } ["VALUE"]=> array(5) { [0]=> string(3) "625" [1]=> string(3) "878" [2]=> string(3) "287" [3]=> string(3) "879" [4]=> string(3) "880" } ["DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(5) { [0]=> string(3) "625" [1]=> string(3) "878" [2]=> string(3) "287" [3]=> string(3) "879" [4]=> string(3) "880" } ["~DESCRIPTION"]=> array(5) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" } ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(5) { [0]=> string(125) "аллогенная трансплантация стволовых клеток" [1]=> string(109) "инвазивные грибковые инфекции (ИГИ)" [2]=> string(68) "профилактика" [3]=> string(89) "инфекционные осложнения" [4]=> string(66) "каспофунгин" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["CONTACT"]=> array(38) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "11987" ["VALUE"]=> string(3) "707" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "707" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(59) "Nicolaus Kröger" ["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) "12003" ["VALUE"]=> array(2) { ["TEXT"]=> string(3471) "<h3>Состояние вопроса</h3> <p> Грибковые инфекции, вызванные <em>Aspergillus</em> or <em>Candida</em>, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы. </p> <h3>Методы</h3> <p>Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана <em>Aspergillus</em> и антител к <em>Candida</em> проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата. </p> <h3>Результаты</h3> <p>Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином. </p> <h3>Выводы</h3> <p>Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3327) "

Состояние вопроса

Грибковые инфекции, вызванные Aspergillus or Candida, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы.

Методы

Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана Aspergillus и антител к Candida проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата.

Результаты

Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином.

Выводы

Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.

" ["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(3327) "

Состояние вопроса

Грибковые инфекции, вызванные Aspergillus or Candida, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы.

Методы

Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана Aspergillus и антител к Candida проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата.

Результаты

Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином.

Выводы

Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.

" } } } }

						Array
(
    [KEYWORDS] => Array
        (
            [ID] => 19
            [TIMESTAMP_X] => 2015-09-03 10:46:01
            [IBLOCK_ID] => 2
            [NAME] => Ключевые слова
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => KEYWORDS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 19
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 4
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => Y
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => Y
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 11700
                    [1] => 11701
                    [2] => 11702
                )

            [VALUE] => Array
                (
                    [0] => 850
                    [1] => 851
                    [2] => 711
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 850
                    [1] => 851
                    [2] => 711
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                )

            [~NAME] => Ключевые слова
            [~DEFAULT_VALUE] => 
        )

    [SUBMITTED] => Array
        (
            [ID] => 20
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата подачи
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUBMITTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 20
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11658
            [VALUE] => 10/30/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10/30/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата подачи
            [~DEFAULT_VALUE] => 
        )

    [ACCEPTED] => Array
        (
            [ID] => 21
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата принятия
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ACCEPTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 21
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11659
            [VALUE] => 12/11/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 12/11/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата принятия
            [~DEFAULT_VALUE] => 
        )

    [PUBLISHED] => Array
        (
            [ID] => 22
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата публикации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PUBLISHED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 22
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11660
            [VALUE] => 12/17/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 12/17/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата публикации
            [~DEFAULT_VALUE] => 
        )

    [CONTACT] => Array
        (
            [ID] => 23
            [TIMESTAMP_X] => 2015-09-03 14:43:05
            [IBLOCK_ID] => 2
            [NAME] => Контакт
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => CONTACT
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 23
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11661
            [VALUE] => 849
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 849
            [~DESCRIPTION] => 
            [~NAME] => Контакт
            [~DEFAULT_VALUE] => 
        )

    [AUTHORS] => Array
        (
            [ID] => 24
            [TIMESTAMP_X] => 2015-09-03 10:45:07
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHORS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 24
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 11703
                    [1] => 11704
                    [2] => 11705
                    [3] => 11706
                    [4] => 11707
                )

            [VALUE] => Array
                (
                    [0] => 845
                    [1] => 846
                    [2] => 847
                    [3] => 848
                    [4] => 849
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 845
                    [1] => 846
                    [2] => 847
                    [3] => 848
                    [4] => 849
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                )

            [~NAME] => Авторы
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_RU] => Array
        (
            [ID] => 25
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 25
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11677
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Сабурова И. Ю., Оникийчук Я. С., Зотова И. И., Сологуб Г. Н., Зарайский М. И.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Авторы
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_RU] => Array
        (
            [ID] => 26
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Организации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 26
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Организации
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_RU] => Array
        (
            [ID] => 27
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Описание/Резюме
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 27
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11678
            [VALUE] => Array
                (
                    [TEXT] => <p class="bodytext">Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Миелопролиферативные заболевания (МПЗ) представляют собой гетерогенную группу нарушений гемопоэза, сопровождающихся множественной гиперплазией клеток костного мозга. Их диагностика сложна и часто основывается на критериях исключения. Одним из наиболее диагностически значимых критериев для МПЗ является наличие мутации V617F в гене JAK2. Основная цель данной статьи – описание скринингового метода детекции V617F в гене JAK2, пригодного для первичной диагностики. Геномная ДНК от 58 пациентов с неверифицированным миелопролиферативным заболеванием выделялась по стандартной технологии. Детекция наличия мутации V617F в гене JAK2 проводилась с использованием двух пар праймеров, специфичных для мутантного и дикого типов генов JAK2. Использовалась клеточная линия UKE1 (Б. Фезе, Германия). Установлено, что представляемая методика выявляет наличие мутации V617F в гене JAK2 с диагностически значимой чувствительностью и специфичностью. Частота мутации в общей группе составила 29,3%. Процент встречаемости мутации V617F в гене JAK2 в группе первичных пациентов с неверифицированным диагнозом МПЗ составил 25,7%. Таким образом, разработанный нами метод определения мутации V617F в гене JAK2 может быть использован в качестве скрининговой диагностики у пациентов с неверифицированными хроническими миелопролиферативными заболеваниями.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Описание/Резюме
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [DOI] => Array
        (
            [ID] => 28
            [TIMESTAMP_X] => 2016-04-06 14:11:12
            [IBLOCK_ID] => 2
            [NAME] => DOI
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => DOI
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 28
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11667
            [VALUE] => 10.3205/ctt-2008-en-000018.01
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10.3205/ctt-2008-en-000018.01
            [~DESCRIPTION] => 
            [~NAME] => DOI
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_EN] => Array
        (
            [ID] => 37
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Author
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 37
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11689
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Irina Y. Saburova, Yana S. Onikiychuk, Irina I. Zotova, Galina N. Sologub, Mikhail I. Zarayskiy
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Author
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_EN] => Array
        (
            [ID] => 38
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Organization
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 38
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11690
            [VALUE] => Array
                (
                    [TEXT] => <p>Saint-Petersburg Pavlov State Medical University, Russia</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Saint-Petersburg Pavlov State Medical University, Russia
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Organization
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_EN] => Array
        (
            [ID] => 39
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Description / Summary
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 39
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11691
            [VALUE] => Array
                (
                    [TEXT] => <p class="bodytext">Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Myeloproliferative disorders (MPD) are a heterogeneous group of hematopoietic diseases accompanied by multiple hyperplasia of bone marrow cells. They are rather difficult for diagnostics and often only revealed by excluding other conditions. One of the most valuable diagnostic criteria for MPD is the V617F mutation of the JAK2 gene. The main subject of this study was to develop a routine detection technique for the JAK2V617F mutation that will be useful for primary diagnostics. To do so, we developed two pairs of primers specific for mutated and wild-type JAK2. To ensure high sensitivity and specificity in JAK2V617F detection we first adjusted the novel PCR technique on the UKE1 cell line previously shown to be homozygous for the JAK2V617F mutation. Next we isolated genomic DNA from 58 MPD patients with different diagnoses using standard techniques. The overall mutation rate in this group was found to be 29.3%. The frequency of the JAK2V617F mutation in newly diagnosed patients with non-verified MPD was 25.7%. We conclude that the detection technique for the JAK2V617F mutation developed in our laboratory represents a useful tool as a diagnostic screening method in patients with myeloproliferative disorders.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Description / Summary
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [NAME_EN] => Array
        (
            [ID] => 40
            [TIMESTAMP_X] => 2015-09-03 10:49:47
            [IBLOCK_ID] => 2
            [NAME] => Name
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 40
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11668
            [VALUE] => Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Detecting the V617F mutation of the Jak2 gene in patients with myeloproliferative disorders
            [~DESCRIPTION] => 
            [~NAME] => Name
            [~DEFAULT_VALUE] => 
        )

    [FULL_TEXT_RU] => Array
        (
            [ID] => 42
            [TIMESTAMP_X] => 2015-09-07 20:29:18
            [IBLOCK_ID] => 2
            [NAME] => Полный текст
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => FULL_TEXT_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 42
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Полный текст
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [PDF_RU] => Array
        (
            [ID] => 43
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF RUS
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_RU
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 43
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11679
            [VALUE] => 500
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 500
            [~DESCRIPTION] => 
            [~NAME] => PDF RUS
            [~DEFAULT_VALUE] => 
        )

    [PDF_EN] => Array
        (
            [ID] => 44
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF ENG
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 44
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11680
            [VALUE] => 501
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 501
            [~DESCRIPTION] => 
            [~NAME] => PDF ENG
            [~DEFAULT_VALUE] => 
        )

    [NAME_LONG] => Array
        (
            [ID] => 45
            [TIMESTAMP_X] => 2023-04-13 00:55:00
            [IBLOCK_ID] => 2
            [NAME] => Название (для очень длинных заголовков)
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_LONG
            [DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 45
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 80
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Название (для очень длинных заголовков)
            [~DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

        )

)
					

						Array
(
    [KEYWORDS] => Array
        (
            [ID] => 19
            [TIMESTAMP_X] => 2015-09-03 10:46:01
            [IBLOCK_ID] => 2
            [NAME] => Ключевые слова
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => KEYWORDS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 19
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 4
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => Y
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => Y
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 11914
                    [1] => 11915
                    [2] => 11916
                    [3] => 11917
                )

            [VALUE] => Array
                (
                    [0] => 856
                    [1] => 163
                    [2] => 857
                    [3] => 858
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 856
                    [1] => 163
                    [2] => 857
                    [3] => 858
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                )

            [~NAME] => Ключевые слова
            [~DEFAULT_VALUE] => 
        )

    [SUBMITTED] => Array
        (
            [ID] => 20
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата подачи
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUBMITTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 20
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11742
            [VALUE] => 08/28/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 08/28/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата подачи
            [~DEFAULT_VALUE] => 
        )

    [ACCEPTED] => Array
        (
            [ID] => 21
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата принятия
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ACCEPTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 21
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11743
            [VALUE] => 11/21/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 11/21/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата принятия
            [~DEFAULT_VALUE] => 
        )

    [PUBLISHED] => Array
        (
            [ID] => 22
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата публикации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PUBLISHED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 22
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11744
            [VALUE] => 12/15/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 12/15/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата публикации
            [~DEFAULT_VALUE] => 
        )

    [CONTACT] => Array
        (
            [ID] => 23
            [TIMESTAMP_X] => 2015-09-03 14:43:05
            [IBLOCK_ID] => 2
            [NAME] => Контакт
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => CONTACT
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 23
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11745
            [VALUE] => 853
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 853
            [~DESCRIPTION] => 
            [~NAME] => Контакт
            [~DEFAULT_VALUE] => 
        )

    [AUTHORS] => Array
        (
            [ID] => 24
            [TIMESTAMP_X] => 2015-09-03 10:45:07
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHORS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 24
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 11918
                    [1] => 11919
                    [2] => 11920
                )

            [VALUE] => Array
                (
                    [0] => 853
                    [1] => 854
                    [2] => 855
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 853
                    [1] => 854
                    [2] => 855
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                )

            [~NAME] => Авторы
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_RU] => Array
        (
            [ID] => 25
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 25
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11758
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Дуросинми М. А., Фалуйи Дж. О., Ойекунле А. А. и соавт.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Авторы
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_RU] => Array
        (
            [ID] => 26
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Организации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 26
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Организации
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_RU] => Array
        (
            [ID] => 27
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Описание/Резюме
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 27
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11759
            [VALUE] => Array
                (
                    [TEXT] => <h3>Цель работы</h3>
<p>Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).</p>
<h3> Методы и клинический материал</h3>
<p> С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток). <br />
<h3>Результаты</h3>
<p> После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043). <br /><h3>Выводы</h3> 
<p>В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях.
</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Цель работы
Оценить клинический ответ и токсичность иматиниба мезилата (Гливека) у нигерийских больных хроническим миелолейкозом (ХМЛ).
 Методы и клинический материал
 С августа 2003 г. по август 2007 г. под наблюдением находились 98 больных с диагнозом ХМЛ (средний возраст 36 лет – от 11 до 65 лет), позитивных по Ph/bcr-abl, давших согласие на терапию, в том числе 56 мужчин и 42 женщины. Независимо от фазы заболевания, лечение Иматинибом проводилось в дозах 300-600 мг в день в госпитале OAU (Нигерия). Ответ на лечение оценивался по клиническим, гематологическим, цитогенетическим и/или молекулярным параметрам. Число клеток в крови проверяли каждые 2 недели в течение первых трех месяцев терапии. Кариотипирование повторяли каждые 6 месяцев. Регистрировали общую выживаемость и частоту полной гематологической ремиссии (ПГР) или большой цитогенетической ремиссии (БЦР, 1-34% Ph+ клеток). 

Результаты
 После 1 и 3 месяцев лечения полная гематологическая ремиссия была достигнута, соответственно, у 64% и 83% больных. При среднем сроке наблюдения 25 месяцев, частота ПГР и БЦР составляла 59% и 35%, соответственно. Спленомегалия и/или гепатомегалия менее 7 см от края ребер были прогностическими признаками в отношении ПГР (соответственно, p = 0.0006 и 0.034). После 12 месяцев наблюдения, общая выживаемость и выживаемость без прогрессии (ВБП) составляла, соответственно, 96% и 91%. Число бластных форм на периферии ниже 5% на момент диагноза и достижение ПГР через 6 мес. были ассоциированы со значительно лучшим выживанием (уровни p были, соответственно, 0.037 and 0.043). 
Выводы
 
В сравнении с обычной химиотерапией и применением альфа-интерферона, как было ранее показано в Нигерии, иматиниб может индуцировать раннюю цитогенетическую ремиссию у Ph/bcr-abl- позитивных больных ХМЛ, при минимальных (побочных) заболеваниях.

                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Описание/Резюме
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [DOI] => Array
        (
            [ID] => 28
            [TIMESTAMP_X] => 2016-04-06 14:11:12
            [IBLOCK_ID] => 2
            [NAME] => DOI
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => DOI
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 28
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11749
            [VALUE] => 10.3205/ctt-2008-en-000027.01
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10.3205/ctt-2008-en-000027.01
            [~DESCRIPTION] => 
            [~NAME] => DOI
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_EN] => Array
        (
            [ID] => 37
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Author
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 37
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11769
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Prof. Muheez A. Durosinmi<sup>1</sup>, Prof. Julius O. Faluyi<sup>2</sup>, Dr. Anthony A. Oyekunle<sup>1</sup>, Dr. Lateef Salawu<sup>1</sup>, Dr. Ismail A. Adediran<sup>1</sup>, Dr. Norah O. Akinola<sup>1</sup>, Oluwakemi O. Bamgbade<sup>3</sup>, Dr. Charles C. Okanny<sup>4</sup>, Dr. Sulaiman Akanmu<sup>4</sup>, Dr. Oche P. Ogbe<sup>5</sup>, Dr. Tambi T. Wakama<sup>5</sup>, Dr. Chijoke A. Nwauche<sup>6</sup>, Dr. Matthew E. Enosolease<sup>7</sup>, Dr. Daye N.K. Halim<sup>7</sup>, Dr. Godwin N. Bazuaye<sup>7</sup>, Dr. Chide E. Okocha<sup>8</sup>, Dr. J. A. Olaniyi<sup>9</sup>, Dr. Titi S. Akingbola<sup>9</sup>, Dr. Victor O. Mabayoje<sup>10</sup>, Dr. Ajani A. Raji<sup>10</sup>, Dr. Aisha Mamman<sup>11</sup>, Dr. Aisha Kuliya-Gwarzo<sup>12</sup>, Dr. Obike G. Ibegbulam<sup>13</sup>, Dr. Sunday Ocheni<sup>13</sup>, Dr. Yohanna Tanko<sup>14</sup>, Dr. Oladimeji P. Arewa<sup>1</sup>, Dr. Rahman A.A. Bolarinwa<sup>1</sup>, Dr. Davidson O. Kassim<sup>1</sup>, Dr. Mohammed A. Ndakotsu<sup>1</sup>, Dr. Omotilewa A. Amusu<sup>15</sup>, Prof. O. O. Akinyanju<sup>16</sup></p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Prof. Muheez A. Durosinmi1, Prof. Julius O. Faluyi2, Dr. Anthony A. Oyekunle1, Dr. Lateef Salawu1, Dr. Ismail A. Adediran1, Dr. Norah O. Akinola1, Oluwakemi O. Bamgbade3, Dr. Charles C. Okanny4, Dr. Sulaiman Akanmu4, Dr. Oche P. Ogbe5, Dr. Tambi T. Wakama5, Dr. Chijoke A. Nwauche6, Dr. Matthew E. Enosolease7, Dr. Daye N.K. Halim7, Dr. Godwin N. Bazuaye7, Dr. Chide E. Okocha8, Dr. J. A. Olaniyi9, Dr. Titi S. Akingbola9, Dr. Victor O. Mabayoje10, Dr. Ajani A. Raji10, Dr. Aisha Mamman11, Dr. Aisha Kuliya-Gwarzo12, Dr. Obike G. Ibegbulam13, Dr. Sunday Ocheni13, Dr. Yohanna Tanko14, Dr. Oladimeji P. Arewa1, Dr. Rahman A.A. Bolarinwa1, Dr. Davidson O. Kassim1, Dr. Mohammed A. Ndakotsu1, Dr. Omotilewa A. Amusu15, Prof. O. O. Akinyanju16
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Author
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_EN] => Array
        (
            [ID] => 38
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Organization
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 38
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11770
            [VALUE] => Array
                (
                    [TEXT] => <p class="bodytext"><sup>1</sup>Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; <sup>2</sup>Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; <sup>3</sup>Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; <sup>4</sup>Department of Haematology, University of Lagos, Nigeria; <sup>5</sup>Department of Haematology, National Hospital, Abuja, Nigeria; <sup>6</sup>Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; <sup>7</sup>Department of Haematology, University of Benin, Nigeria; <sup>8</sup>Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; <sup>9</sup>Department of Haematology, University College Hospital, Ibadan, Nigeria; <sup>10</sup>Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; <sup>11</sup>Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, <sup>12</sup>Department of Haematology, Bayero University,  Kano, Nigeria; <sup>13</sup>Department of Haematology, University of Nigeria, Enugu, Nigeria; <sup>14</sup>Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; <sup>15</sup>Department of Haematology, Army Reference Hospital, Lagos, Nigeria; <sup>16</sup>Asaju Medical Clinic, Victoria Island, Lagos, Nigeria</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
1Department of Haematology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria; 2Department of Botany, Obafemi Awolowo University, Ile-Ife, Nigeria; 3Department of Pharmacy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria; 4Department of Haematology, University of Lagos, Nigeria; 5Department of Haematology, National Hospital, Abuja, Nigeria; 6Department of Haematology, University of Port-Harcourt, Port-Harcourt, Nigeria; 7Department of Haematology, University of Benin, Nigeria; 8Department of Haematology, Nnamdi Azikiwe University, Nnewi, Nigeria; 9Department of Haematology, University College Hospital, Ibadan, Nigeria; 10Department of Haematology, Ladoke Akintola University of Technology, Osogbo, Nigeria; 11Department of Haematology, Ahmadu Bello University, Zaria, Nigeria, 12Department of Haematology, Bayero University,  Kano, Nigeria; 13Department of Haematology, University of Nigeria, Enugu, Nigeria; 14Department of Haematology, Gwagwalada Specialist Hospital, Abuja, Nigeria; 15Department of Haematology, Army Reference Hospital, Lagos, Nigeria; 16Asaju Medical Clinic, Victoria Island, Lagos, Nigeria
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Organization
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_EN] => Array
        (
            [ID] => 39
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Description / Summary
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 39
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11778
            [VALUE] => Array
                (
                    [TEXT] => <h3>Objectives</h3>
<p>To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia. <br /></p>
<h3>Methods</h3>
<p>From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  </p>
<h3>Results</h3>
<p>Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043). </p>
<h3>Conclusions</h3>
<p>Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Objectives
To assess response and toxicity to Imatinib mesylate (Glivec) in Nigerian Patients with chronic myeloid leukemia. 

Methods
From August 2003 to August 2007, 98 consecutive, consenting patients, 56 (57%) males and 42 (43%) females, median age 36 years (range, 11-65 years) diagnosed with  CML, irrespective of disease phase received Imatinib at a dose of 300-600mg/day at the OAU Teaching Hospitals, Nigeria. Response to therapy was assessed by clinical, haematological and cytogenetic parameters. Blood counts were checked every two weeks in the first three months of therapy. Chromosome analysis was repeated sixth monthly. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated.  
Results
Complete haematologic remission was achieved in 64% and 83% of patients at one and three months, respectively. With a median follow-up of 25 months, the rates of CCR and MCR were 59% and 35% respectively. At 12 months of follow-up, OS and progression- free survival (PFS) were 96% and 91%, respectively. Achievement of CR at six months was associated with significantly better survival (p = 0.043). 
Conclusions
Compared to treatment outcome with conventional chemotherapy and alpha interferon, as previously used in Nigeria, the results obtained with this regimen has established Imatinib as the first-line treatment strategy in patients with CML, as it is in other populations, with minimal morbidity.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Description / Summary
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [NAME_EN] => Array
        (
            [ID] => 40
            [TIMESTAMP_X] => 2015-09-03 10:49:47
            [IBLOCK_ID] => 2
            [NAME] => Name
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 40
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11750
            [VALUE] => The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => The use of Imatinib mesylate in Nigerians with chronic myeloid leukemia
            [~DESCRIPTION] => 
            [~NAME] => Name
            [~DEFAULT_VALUE] => 
        )

    [FULL_TEXT_RU] => Array
        (
            [ID] => 42
            [TIMESTAMP_X] => 2015-09-07 20:29:18
            [IBLOCK_ID] => 2
            [NAME] => Полный текст
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => FULL_TEXT_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 42
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Полный текст
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [PDF_RU] => Array
        (
            [ID] => 43
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF RUS
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_RU
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 43
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11760
            [VALUE] => 504
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 504
            [~DESCRIPTION] => 
            [~NAME] => PDF RUS
            [~DEFAULT_VALUE] => 
        )

    [PDF_EN] => Array
        (
            [ID] => 44
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF ENG
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 44
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11761
            [VALUE] => 505
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 505
            [~DESCRIPTION] => 
            [~NAME] => PDF ENG
            [~DEFAULT_VALUE] => 
        )

    [NAME_LONG] => Array
        (
            [ID] => 45
            [TIMESTAMP_X] => 2023-04-13 00:55:00
            [IBLOCK_ID] => 2
            [NAME] => Название (для очень длинных заголовков)
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_LONG
            [DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 45
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 80
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Название (для очень длинных заголовков)
            [~DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

        )

)
					

						Array
(
    [KEYWORDS] => Array
        (
            [ID] => 19
            [TIMESTAMP_X] => 2015-09-03 10:46:01
            [IBLOCK_ID] => 2
            [NAME] => Ключевые слова
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => KEYWORDS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 19
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 4
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => Y
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => Y
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 11904
                    [1] => 11905
                    [2] => 11906
                    [3] => 11907
                )

            [VALUE] => Array
                (
                    [0] => 686
                    [1] => 863
                    [2] => 864
                    [3] => 865
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 686
                    [1] => 863
                    [2] => 864
                    [3] => 865
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                )

            [~NAME] => Ключевые слова
            [~DEFAULT_VALUE] => 
        )

    [SUBMITTED] => Array
        (
            [ID] => 20
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата подачи
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUBMITTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 20
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11825
            [VALUE] => 10/10/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10/10/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата подачи
            [~DEFAULT_VALUE] => 
        )

    [ACCEPTED] => Array
        (
            [ID] => 21
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата принятия
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ACCEPTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 21
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11826
            [VALUE] => 11/13/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 11/13/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата принятия
            [~DEFAULT_VALUE] => 
        )

    [PUBLISHED] => Array
        (
            [ID] => 22
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата публикации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PUBLISHED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 22
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11827
            [VALUE] => 12/10/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 12/10/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата публикации
            [~DEFAULT_VALUE] => 
        )

    [CONTACT] => Array
        (
            [ID] => 23
            [TIMESTAMP_X] => 2015-09-03 14:43:05
            [IBLOCK_ID] => 2
            [NAME] => Контакт
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => CONTACT
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 23
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11828
            [VALUE] => 833
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 833
            [~DESCRIPTION] => 
            [~NAME] => Контакт
            [~DEFAULT_VALUE] => 
        )

    [AUTHORS] => Array
        (
            [ID] => 24
            [TIMESTAMP_X] => 2015-09-03 10:45:07
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHORS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 24
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 11908
                    [1] => 11909
                    [2] => 11910
                    [3] => 11911
                    [4] => 11912
                    [5] => 11913
                )

            [VALUE] => Array
                (
                    [0] => 830
                    [1] => 860
                    [2] => 831
                    [3] => 861
                    [4] => 833
                    [5] => 862
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                    [5] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 830
                    [1] => 860
                    [2] => 831
                    [3] => 861
                    [4] => 833
                    [5] => 862
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                    [5] => 
                )

            [~NAME] => Авторы
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_RU] => Array
        (
            [ID] => 25
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 25
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11847
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Шипунова (Нифонтова) И. Н., Сац Н. В., Свинарева Д. А., Петрова Т. В., Дризе Н. И., Савченко В. Г.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Авторы
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_RU] => Array
        (
            [ID] => 26
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Организации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 26
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Организации
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_RU] => Array
        (
            [ID] => 27
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Описание/Резюме
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 27
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11848
            [VALUE] => Array
                (
                    [TEXT] => <h3>Введение</h3> 
<p>Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).</p>
<h3>Материалы и методы</h3>
<p> В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену <em>smc</em>, сцепленному с полом, или по маркеру <em>hADA</em>, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода.  <br /></p>
<h3>Результаты</h3>
<p>Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р&lt;0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ. <br /></p><h3>Заключение</h3>
<p>Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Введение
 
Предыдущие исследования показали, что кроветворение у мышей, которым пересаживали гемопоэтические стволовые клетки (ГСК), маркированными ретровирусным материалом, восстанавливается за счет множества короткоживущих клонов. Такая клональная кинетика предполагает истощение гемопоэтических клонов с последующим рекрутированием новых клонов путем их пролиферации (клональная сукцессия).
Материалы и методы
 В данном исследовании, клональный гемопоэз изучали в модельных опытах на мышах, причем восстановление гемопоэза исследовали, вводя вирус-инфицированные клетки костного мозга (КМ), экспрессирующие ген АДА человека, или ГСК от донора другого пола. Экспериментальные животные подвергались облучению в летальной дозе и трансплантации маркированных ГСК от мышей-доноров. Определение селезеночных колоний (КОЕ-с) у мышей-реципиентов (самок) проводили по Тиллу и Мак-Каллоху. Происхождение КОЕ-с у мышей после трансплантации отслеживали по гену smc, сцепленному с полом, или по маркеру hADA, трансдуцированному в донорские клетки. Введение Г-КСФ после трансплантации проводили ежемесячно в течение полугода.  

Результаты
Повторное введение Г-КСФ не влияло на число лейкоцитов и долю гранулоцитов в периферической крови после трансплантации. Концентрация КОЕ-с в костном мозге трансплантированных мышей не изменялась после введения Г-КСФ. Полный донорский химеризм развивался редко, обычно наблюдалось частичное возвращение к кроветворению реципиента. Доля донорских КОЕ-с от месяца к месяцу колебалась между 35 и 88%. У трансплантированных мышей, не получавших Г-КСФ, доля донорских КОЕ-с была значительно выше, чем в группе, леченной Г-КСФ (71.2±6.9% против 56.5±5.3%, р<0.05). Доля донорских КОЕ-с, маркированных hADA, в группе, получавшей Г-КСФ, была более низкой и более стабильной, чем у «нелеченых» животных (20.6±7.1% versus 45.7±6.3%). Анализ отдельных клонов у «леченых» и «нелеченых» животных не выявил достоверных различий по их среднему содержанию. Однако величина клонов существенно снижалась при введении Г-КСФ, так как клоны были представлены меньшим числом колоний. Долгоживущие клоны (выявляемые после 3 мес.) не наблюдались после длительного введения Г-КСФ. 
Заключение
Повторные инъекции Г-КСФ в фармакологических дозах вызывают дисбаланс в кроветворной системе. Долгосрочные последствия мобилизации ГСК посредством Г-КСФ следует внимательно отслеживать у потенциальных доноров.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Описание/Резюме
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [DOI] => Array
        (
            [ID] => 28
            [TIMESTAMP_X] => 2016-04-06 14:11:12
            [IBLOCK_ID] => 2
            [NAME] => DOI
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => DOI
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 28
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11835
            [VALUE] => 10.3205/ctt-2008-en-000017.01 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10.3205/ctt-2008-en-000017.01 
            [~DESCRIPTION] => 
            [~NAME] => DOI
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_EN] => Array
        (
            [ID] => 37
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Author
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 37
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11871
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Irina Shipounova (Nifontova), Natalia Sats, Daria Svinareva, Tatiana Petrova, Nina Drize, Valeriy Savchenko
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Author
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_EN] => Array
        (
            [ID] => 38
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Organization
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 38
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11872
            [VALUE] => Array
                (
                    [TEXT] => <p>National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
National Hematology Research Center, Russian Academy of Medical Science, Moscow, Russia
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Organization
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_EN] => Array
        (
            [ID] => 39
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Description / Summary
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 39
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11873
            [VALUE] => Array
                (
                    [TEXT] => <p class="bodytext">The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses<br> of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system.
</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
The clonal composition of hematopoietic tissue was studied in chimeras reconstituted with bone marrow cells expressing the human adenosine deaminase gene after repeated rounds of G-CSF treatment. Six courses
 of G-CSF treatment led to an insignificant decrease of clone numbers and a considerable reduction in clone size and lifespan. The data suggest that the dissociation of the hematopoietic stem cells from their microenvironment after G-CSF treatment resulted in the exhaustion of clone size, and a decrease in the proliferative potential of the hematopoietic stem cells. Repeated G-CSF treatment adversely affects the hematopoietic system.

                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Description / Summary
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [NAME_EN] => Array
        (
            [ID] => 40
            [TIMESTAMP_X] => 2015-09-03 10:49:47
            [IBLOCK_ID] => 2
            [NAME] => Name
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 40
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11836
            [VALUE] => Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Clonal composition of hematopoietic tissue in reconstituted mice after repeated treatment with G-CSF
            [~DESCRIPTION] => 
            [~NAME] => Name
            [~DEFAULT_VALUE] => 
        )

    [FULL_TEXT_RU] => Array
        (
            [ID] => 42
            [TIMESTAMP_X] => 2015-09-07 20:29:18
            [IBLOCK_ID] => 2
            [NAME] => Полный текст
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => FULL_TEXT_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 42
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Полный текст
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [PDF_RU] => Array
        (
            [ID] => 43
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF RUS
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_RU
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 43
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11849
            [VALUE] => 509
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 509
            [~DESCRIPTION] => 
            [~NAME] => PDF RUS
            [~DEFAULT_VALUE] => 
        )

    [PDF_EN] => Array
        (
            [ID] => 44
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF ENG
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 44
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11850
            [VALUE] => 510
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 510
            [~DESCRIPTION] => 
            [~NAME] => PDF ENG
            [~DEFAULT_VALUE] => 
        )

    [NAME_LONG] => Array
        (
            [ID] => 45
            [TIMESTAMP_X] => 2023-04-13 00:55:00
            [IBLOCK_ID] => 2
            [NAME] => Название (для очень длинных заголовков)
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_LONG
            [DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 45
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 80
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Название (для очень длинных заголовков)
            [~DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

        )

)
					

						Array
(
    [KEYWORDS] => Array
        (
            [ID] => 19
            [TIMESTAMP_X] => 2015-09-03 10:46:01
            [IBLOCK_ID] => 2
            [NAME] => Ключевые слова
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => KEYWORDS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 19
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 4
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => Y
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => Y
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 12220
                    [1] => 12221
                    [2] => 12222
                    [3] => 12223
                    [4] => 12224
                )

            [VALUE] => Array
                (
                    [0] => 625
                    [1] => 878
                    [2] => 287
                    [3] => 879
                    [4] => 880
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 625
                    [1] => 878
                    [2] => 287
                    [3] => 879
                    [4] => 880
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                )

            [~NAME] => Ключевые слова
            [~DEFAULT_VALUE] => 
        )

    [SUBMITTED] => Array
        (
            [ID] => 20
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата подачи
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUBMITTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 20
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11984
            [VALUE] => 10/17/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10/17/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата подачи
            [~DEFAULT_VALUE] => 
        )

    [ACCEPTED] => Array
        (
            [ID] => 21
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата принятия
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ACCEPTED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 21
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11985
            [VALUE] => 11/21/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 11/21/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата принятия
            [~DEFAULT_VALUE] => 
        )

    [PUBLISHED] => Array
        (
            [ID] => 22
            [TIMESTAMP_X] => 2015-09-02 17:21:42
            [IBLOCK_ID] => 2
            [NAME] => Дата публикации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PUBLISHED
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 22
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => DateTime
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 11986
            [VALUE] => 11/28/2008 12:00:00 am
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 11/28/2008 12:00:00 am
            [~DESCRIPTION] => 
            [~NAME] => Дата публикации
            [~DEFAULT_VALUE] => 
        )

    [CONTACT] => Array
        (
            [ID] => 23
            [TIMESTAMP_X] => 2015-09-03 14:43:05
            [IBLOCK_ID] => 2
            [NAME] => Контакт
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => CONTACT
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 23
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 11987
            [VALUE] => 707
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 707
            [~DESCRIPTION] => 
            [~NAME] => Контакт
            [~DEFAULT_VALUE] => 
        )

    [AUTHORS] => Array
        (
            [ID] => 24
            [TIMESTAMP_X] => 2015-09-03 10:45:07
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHORS
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => E
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => Y
            [XML_ID] => 24
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 3
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => EAutocomplete
            [USER_TYPE_SETTINGS] => Array
                (
                    [VIEW] => E
                    [SHOW_ADD] => Y
                    [MAX_WIDTH] => 0
                    [MIN_HEIGHT] => 24
                    [MAX_HEIGHT] => 1000
                    [BAN_SYM] => ,;
                    [REP_SYM] =>  
                    [OTHER_REP_SYM] => 
                    [IBLOCK_MESS] => N
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => Array
                (
                    [0] => 12225
                    [1] => 12226
                    [2] => 12227
                    [3] => 12228
                    [4] => 12229
                    [5] => 12230
                    [6] => 12231
                    [7] => 12232
                    [8] => 12233
                    [9] => 12234
                    [10] => 12235
                    [11] => 12236
                    [12] => 12237
                    [13] => 12238
                )

            [VALUE] => Array
                (
                    [0] => 867
                    [1] => 868
                    [2] => 41
                    [3] => 869
                    [4] => 870
                    [5] => 871
                    [6] => 872
                    [7] => 873
                    [8] => 874
                    [9] => 875
                    [10] => 876
                    [11] => 877
                    [12] => 11
                    [13] => 707
                )

            [DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                    [5] => 
                    [6] => 
                    [7] => 
                    [8] => 
                    [9] => 
                    [10] => 
                    [11] => 
                    [12] => 
                    [13] => 
                )

            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [0] => 867
                    [1] => 868
                    [2] => 41
                    [3] => 869
                    [4] => 870
                    [5] => 871
                    [6] => 872
                    [7] => 873
                    [8] => 874
                    [9] => 875
                    [10] => 876
                    [11] => 877
                    [12] => 11
                    [13] => 707
                )

            [~DESCRIPTION] => Array
                (
                    [0] => 
                    [1] => 
                    [2] => 
                    [3] => 
                    [4] => 
                    [5] => 
                    [6] => 
                    [7] => 
                    [8] => 
                    [9] => 
                    [10] => 
                    [11] => 
                    [12] => 
                    [13] => 
                )

            [~NAME] => Авторы
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_RU] => Array
        (
            [ID] => 25
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Авторы
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 25
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 12002
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,<br> фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Штуте Н., Забелина Т., Фезе Б., Хассенпфлюг В., Панзе Й., Вольшке К., Айюк Ф., Шидер Х., Ренгес Х., Кратохвилл А.,
 фон Хинюбер Р., Эрттманн Р., Цандер А.Р., Крегер Н.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Авторы
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_RU] => Array
        (
            [ID] => 26
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Организации
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 26
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Организации
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_RU] => Array
        (
            [ID] => 27
            [TIMESTAMP_X] => 2015-09-02 18:01:20
            [IBLOCK_ID] => 2
            [NAME] => Описание/Резюме
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 27
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 12003
            [VALUE] => Array
                (
                    [TEXT] => <h3>Состояние вопроса</h3>
<p> Грибковые инфекции, вызванные <em>Aspergillus</em> or <em>Candida</em>, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы. </p>
<h3>Методы</h3>
<p>Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана <em>Aspergillus</em> и антител к <em>Candida</em> проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата. </p>
<h3>Результаты</h3>
<p>Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином. </p>
<h3>Выводы</h3>
<p>Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Состояние вопроса
 Грибковые инфекции, вызванные Aspergillus or Candida, поражают, главным образом, легкие и являются основной причиной смертности при трансплантации стволовых клеток (ТСК). Больные с анамнезом или риском развития инвазивных грибковых инфекций (ИГИ), при аллогенной трансплантации стволовых клеток имеют высокий риск реактивации или прогрессии этих инфекций. В проспективном исследовании мы оценивали эффективность и безопасность каспофунгина в качестве вторичной профилактики или лечения персистирующего заболеванимя. Каспофунгин - это эхинокандин, нарушающий сборку клеточной стенки грибка посредством ингибирования β(1,3)-D-глюкансинтазы. 
Методы
Двадцать восемь больных были включены в это исследование, все они были с острым лейкозом. В период ТСК, 16 больных не имели симптомов инфекции, тогда как в 12 случаях (с помощью компьютерной томографии) были отмечены признаки цветущих грибковых инфекций. До начала исследования проводился бронхоальвеолярный лаваж и УЗИ абдоминальной области. Контрольные определения галактоманнана Aspergillus и антител к Candida проводили еженедельно. Каспофунгин (по 50 мг вдень вводили внутривенно от начала кондиционирования до стабильного приживления трансплантата. 
Результаты
Ни у одного из больных не проявлялось побочных эффектов, ведущих к прерыванию лечения каспофунгином. У 14 из 16 больных (88%) без признаков активной инфекции в начале трансплантации не наблюдалось грибковой инфекции после профилактики каспофунгином. В 10 из 12 случаев (83%) с радиологическими признаками активной грибковой инфекции, наблюдаемыми до трансплантации, были получены полные (n=4) или частичные (n=6) ответы после лечения каспофунгином. 
Выводы
Применение каспофунгина безопасно и эффективно у больных высокого риска с ИГИ в анамнезе.
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Описание/Резюме
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [DOI] => Array
        (
            [ID] => 28
            [TIMESTAMP_X] => 2016-04-06 14:11:12
            [IBLOCK_ID] => 2
            [NAME] => DOI
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => DOI
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 28
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 12004
            [VALUE] => 10.3205/ctt-2008-en-000021.01
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 10.3205/ctt-2008-en-000021.01
            [~DESCRIPTION] => 
            [~NAME] => DOI
            [~DEFAULT_VALUE] => 
        )

    [AUTHOR_EN] => Array
        (
            [ID] => 37
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Author
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => AUTHOR_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 37
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 12046
            [VALUE] => Array
                (
                    [TEXT] => <p class="Autor">N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
N. Stute, T. Zabelina, N. Fehse, W. Hassenpflug, J. Panse, C. Wolschke, F. Ayuk, H. Schieder, H. Renges, A. Kratochwille, R. von Hinüber, R. Erttmann, A.R. Zander, N. Kröger
                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Author
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [ORGANIZATION_EN] => Array
        (
            [ID] => 38
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Organization
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => ORGANIZATION_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 38
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 12047
            [VALUE] => Array
                (
                    [TEXT] => <p class="bodytext">Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
</p>
<br>
<p class="bodytext"><b>Correspondence:</b><br> Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.rovsikivDyoi2yrm1leqfyvk2hi');" class="mail">nkroeger@<span style="display:none;">spam is bad</span>uke.uni-hamburg.de</a>
</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Dept of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany



Correspondence:
 Prof.  Dr. med. Nicolaus Kröger, Bone Marrow Transplant Center, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany, Tel.: +49-40-42803 5864, Fax: +49-40-42803 3795, E-mail: nkroeger@spam is baduke.uni-hamburg.de

                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Organization
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [SUMMARY_EN] => Array
        (
            [ID] => 39
            [TIMESTAMP_X] => 2015-09-02 18:02:59
            [IBLOCK_ID] => 2
            [NAME] => Description / Summary
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => SUMMARY_EN
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 39
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 12048
            [VALUE] => Array
                (
                    [TEXT] => <h3>Background</h3>
<p>Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.</p>
<h3>Methods</h3>
<p>Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. </p>
<h3>Results</h3>
<p>No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. </p><h3>Conclusions</h3>
<p>The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.</p>
</p>
                    [TYPE] => HTML
                )

            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Array
                (
                    [TEXT] => 
Background
Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression. In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.
Methods
Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment. 
Results
No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88%) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83%) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved. 
Conclusions
The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.

                    [TYPE] => HTML
                )

            [~DESCRIPTION] => 
            [~NAME] => Description / Summary
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [NAME_EN] => Array
        (
            [ID] => 40
            [TIMESTAMP_X] => 2015-09-03 10:49:47
            [IBLOCK_ID] => 2
            [NAME] => Name
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 80
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 40
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => Y
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 12005
            [VALUE] => Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => Caspofungin as secondary prophylaxis or therapy in patients undergoing allogeneic stem cell transplantation with a prior or ongoing history of systemic or invasive fungal infections
            [~DESCRIPTION] => 
            [~NAME] => Name
            [~DEFAULT_VALUE] => 
        )

    [FULL_TEXT_RU] => Array
        (
            [ID] => 42
            [TIMESTAMP_X] => 2015-09-07 20:29:18
            [IBLOCK_ID] => 2
            [NAME] => Полный текст
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => FULL_TEXT_RU
            [DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 42
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 200
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Полный текст
            [~DEFAULT_VALUE] => Array
                (
                    [TEXT] => 
                    [TYPE] => HTML
                )

        )

    [PDF_RU] => Array
        (
            [ID] => 43
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF RUS
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_RU
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 43
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 12025
            [VALUE] => 521
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 521
            [~DESCRIPTION] => 
            [~NAME] => PDF RUS
            [~DEFAULT_VALUE] => 
        )

    [PDF_EN] => Array
        (
            [ID] => 44
            [TIMESTAMP_X] => 2015-09-09 16:05:20
            [IBLOCK_ID] => 2
            [NAME] => PDF ENG
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => PDF_EN
            [DEFAULT_VALUE] => 
            [PROPERTY_TYPE] => F
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 44
            [FILE_TYPE] => doc, txt, rtf, pdf
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => 
            [USER_TYPE_SETTINGS] => 
            [HINT] => 
            [PROPERTY_VALUE_ID] => 12026
            [VALUE] => 522
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 522
            [~DESCRIPTION] => 
            [~NAME] => PDF ENG
            [~DEFAULT_VALUE] => 
        )

    [NAME_LONG] => Array
        (
            [ID] => 45
            [TIMESTAMP_X] => 2023-04-13 00:55:00
            [IBLOCK_ID] => 2
            [NAME] => Название (для очень длинных заголовков)
            [ACTIVE] => Y
            [SORT] => 500
            [CODE] => NAME_LONG
            [DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

            [PROPERTY_TYPE] => S
            [ROW_COUNT] => 1
            [COL_COUNT] => 30
            [LIST_TYPE] => L
            [MULTIPLE] => N
            [XML_ID] => 45
            [FILE_TYPE] => 
            [MULTIPLE_CNT] => 5
            [TMP_ID] => 
            [LINK_IBLOCK_ID] => 0
            [WITH_DESCRIPTION] => N
            [SEARCHABLE] => N
            [FILTRABLE] => N
            [IS_REQUIRED] => N
            [VERSION] => 1
            [USER_TYPE] => HTML
            [USER_TYPE_SETTINGS] => Array
                (
                    [height] => 80
                )

            [HINT] => 
            [PROPERTY_VALUE_ID] => 
            [VALUE] => 
            [DESCRIPTION] => 
            [VALUE_ENUM] => 
            [VALUE_XML_ID] => 
            [VALUE_SORT] => 
            [~VALUE] => 
            [~DESCRIPTION] => 
            [~NAME] => Название (для очень длинных заголовков)
            [~DEFAULT_VALUE] => Array
                (
                    [TYPE] => HTML
                    [TEXT] => 
                )

        )

)