Acute myeloid leukemia (AML) is the second most common type of leukemia in children and accounts for up to 20 % of all leukemias. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective, and sometimes the only therapeutic option in high-risk patients with AML. Graft-versus-host disease (GVHD) is a major complication of allo-HSCT and the main cause of transplant-related mortality. GVHD prophylaxis in children includes calcineurin inhibitors, either alone or in combination with other immunosuppressants, which can lead to grade II–IV acute GVHD in 40–85 % of cases. Alternatively, GVHD can be prevented with high-dose cyclophosphamide (50 mg/kg/day) administered on days +3, +4 after allo-HSCT, either alone or in combination with other immunosuppressive drugs depending on HLA compatibility of the donor. The aim of this study was to evaluate outcomes after allo-HSCT from an unrelated donor with GVHD prophylaxis with post-transplant cyclophosphamide (PTC) in children in their first and second remission of AML in comparison with a historical control group. We retrospectively analyzed patient outcomes after 53 first-time allo-HSCTs from HLA-matched (n = 40) and partially-matched (8–9/10) (n = 13) unrelated donors performed in pediatric patients (aged 0 to 18 years) in their 1 st or 2 nd remission of AML at the R. M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation from 2008 to 2018. The study was approved by the Independent Ethics Committee and the Scientific Council of the I. P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation. Our group of interest included 26 patients preventively treated for GVHD with 50 mg/kg of cyclophosphamide on days +3 and +4 in combination with calcineurin inhibitors (cyclosporin A – 2 (7.7 %) patients, tacrolimus – 24 (92.3 %) patients), the mTOR inhibitor sirolimus (5 (19.2 %) patients) or mycophenolate mofetil (21 (80.8 %) patients). The historical control group was made up of 27 patients whose GVHD prophylaxis was based on antithymocyte globulin used in combination with calcineurin inhibitors (tacrolimus – 5 (18.5 %) patients, cyclosporin A – 21 (77.8 %) patients) or the mTOR inhibitor sirolimus (1 (3.7 %) patients) or methotrexate (25 (92.6 %) patients), or mycophenolate mofetil (2 (7.4 %) patients). The groups were matched for diagnosis, age, disease status before allo-HSCT, the matched-to-partially-matched donor ratio, the source of hematopoietic stem cells and conditioning regimen intensity (myeloablative conditioning regimen (MAC) or reduced intensity conditioning regimen (RIC)). The median age at the time of allo-HSCT was 8.6 (0.97–18) years in the PTC group and 6.55 (1.42–17.76) years in the historical control group. In the PTC group, 21 (80.8 %) patients were diagnosed with primary AML and 5 (19.2 %) – with secondary AML, while the historical control group included 22 (81.5 %) and 5 (18.5 %) patients with primary and secondary AML respectively. Disease status at the time of allo-HSCT: 21 (80.8 %) patients treated with PTC were in the 1 st complete clinical and hematologic remission (CCHR) and 5 (19.2 %) – in the 2 nd CCHR; among the controls, there were 19 (70.4 %) cases of the 1 st CCHR and 8 (29.6 %) cases of the 2 nd CCHR. In the PTC group, 18 (69.2 %) patients underwent allo-HSCT from 10/10 fully HLA gene-matched donors and 8 (30.8 %) – from 9/10 HLA-matched donors. In the historical control group, 19 (70.4 %) patients had allo-HSCT from 10/10 fully HLA gene-matched donors, 4 (14.8 %) – from 9/10 matched donors, and 1 (3.7 %) – from an 8/10 matched donor. In the PTC group, MAC was used in 14 (53.8 %) patients, RIC – in 12 (46.2 %) patients. In the control group, MAC and RIC were used in 14 (51.9 %) and 13 (48.1 %) patients respectively. In the group treated with PTC, hematopoietic stem cells were derived from the bone marrow in 14 (53.8 %) patients, from the peripheral blood – in 12 (46.2 %) patients. In the historical group, bone marrow was used in 13 (48.1 %) patients and peripheral blood - in 14 patients (51.9 %). The median graft cellularity (CD34+ × 10 6 /kg) in the PTC group was 4.60 (1.7–10.9) × 10 6 /kg, in the historical group – 6.60 (1.0–13.2) × 10 6 /kg. The overall and relapse-free 5-year survival rates were higher in the PTC group than in the historical control group: 83.3 % (95 % confidence interval (CI) 60.9–93.5) vs 59.3 % (95 % CI 38.6–75.0), p = 0.0327 and 76.9 % (95 % CI 55.7–88.9) vs 48.1 % (95 % CI 28.7–65.2), respectively, p = 0.0198. The cumulative incidence of grade II–IV acute GVHD and grade III–IV acute GVHD by day +125 and of moderate and severe chronic GVHD, and the 2-year transplant-related mortality were significantly lower in the PTC group compared to the controls: 15.4 % (95 % CI 4.8–31.5) vs 51.8 % (95 % CI 31,9–68.5), p = 0.004; 7.7 % (95 % CI 1.3–21.7) vs 33.3 (95 % CI 16.8–50.9), p = 0.026; 23.4 % (95 % CI 9.5-41.0) vs 58.6 % (95 % CI 33.8–76.8), p = 0.022; 3.8 % (95 % CI 0.3–16.4) vs 25.9 % (95 % CI 11.5–43.1), p = 0.0232, respectively. GVHD-related mortality was higher in the historical control group than in the PTC group (3.8 % vs 18.5 %, p = 0.192). Thus, PTC-based GVHD prophylaxis was shown to be more effective in managing acute and chronic GVHD compared to antithymocyte globulin, with better overall, relapse-free and GVHD-free relapse-free survival rates and low transplant-related mortality.

Aim. To demonstrate diagnostic and prognostic significance of series measurement of WT1 expression in patients with acute myeloid leukemia (AML) after allogenic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The clinical trial included 88 AML patients (38 females (43 %) and 50 males (57 %) aged 2-68, median 30 years). All the patients received allo-HSCT. Bone marrow was aspirated before (D0) and after HSCT (D+30, D+60, and D+100). Results. The univariate analysis showed statistically significant differences in 2-year overall survival with respect to the following factors: with and without remission at the moment of HSCT (p < 0.001), with and without chronic graft vs. host disease (cGVHD) (p = 0.002), primary or secondary (MDS) AML (p = 0.028), WT1 gene expression < and > 250 copies before HSCT (p < 0.001) and at time points D+60 (p = 0.012), and D+100 (p < 0.001). Multivariate analysis revealed similar statistical significance of differences among patients transplanted in remission (p = 0.041) and with cGVHD (p = 0.03). In univariate analysis statistically significant differences in 2-year event-free survival (EFS) were found: a) in patients with allo-HSCT, either in remission or not (p < 0.001); b) using HSC, but not bone marrow, as transplant source (p < 0.026); c) with normal or high WT1 expression at the stage of HSCT (p < 0.001) and at time point D+100 (p < 0.001); d) using HSC from related or unrelated donor (p = 0.006); e) in patients with cGVHD (p = 0.05). In multivariate analysis independent positive effect on EFS was observed only in patients with normal WT1 expression at D+100 (p = 0.011) and with cGVHD (p = 0.038). Cumulative incidence of posttransplant relapse (PTR) in AML patients with normal or high WT1 expression at the stage of HSCT within the 2-year follow-up was significantly different (28.2 vs. 58.9 %; p = 0.002), also in measurements of this parameter at D+60 and D+100 (p = 0.015 and p < 0.001, respectively). In 1/4 of patients cytological relapses (cPTR) appeared considerably later than molecular relapses (mPTR), i.e. 13-489 days later (median 35 days), which is accounted for by early preventive therapy aimed at cPTR prophylaxis against the background of already recorded mPTR. According to our data, GVHD plays a crucial role in cPTR management. Conclusion. Phenomenon of WT1 expression normalization after allo-HSCT in AML patients proves to have a high diagnostic and prognostic significance. Introduction of this approach into clinical practice seems highly advisable for national oncohematological centers.

Background. Although the use of methotrexate (MTX) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) was compared in a large number of studies, the published results are contradictory. This fact provides ground for the present retrospective single-center trial comparing these two approaches in GVHD prophylaxis. Materials & Methods. The present study included 294 allo-HSC recipients with MTX prophylaxis and 172 allo-HSC recipients with MMF prophylaxis. 36 % of patients underwent matched related donor transplantation, and 64 % of patients received matched unrelated donor transplantation. Results. Univariate and multivariate analyses showed that probability of acute grade 2-4 GVHD was 36 % vs. 39 % (hazard ratio [HR] 1.297; 95% confidence interval [95% CI] 0.931-1.795; p = 0.122), grade 3-4 GVHD was 21 % vs. 25 % (HR 1.472; 95% CI 0.951-2.256; p = 0.05), and probability of chronic GVHD was 52 % vs. 55 % (HR 0.978; 95% CI 0.951-1.406; p = 0.91). In the MTX and MMF groups there were no significant differences in transplantation mortality (HR 1.173; 95% CI 0.797-1.708; p = 0.43), relapse incidence (HR 1.034; 95% CI 0.743-1.428; p = 0.84), overall survival (HR 1.087; 95% CI 0.825-1.433; p = 0.55), event-free survival (HR 1.108; 95% CI 0.854-1.437; p = 0.43), disease and GVHD free survival (HR 1.065; 95% CI 0.845-1.343; p = 0.59). Engraftment occurred earlier when MMF was used (p = 0.035). Administration of MMF instead of MTX was associated with lower probability of grade 3-4 toxic hepatitis (7 % vs. 31 %; p < 0.0001) and grade 3-4 mucositis (23 % vs. 45 %; p = 0.0002). Conclusion. The efficacy of GVHD prophylaxis using MMF is comparable with that of MTX, but MMF is associated with a better safety profile due to reduced incidence of severe liver toxicity and mucositis.

Контактная информация: Щербаков Александр Александрович – врач анестезиолог-реаниматолог ОРиИТ No 3, НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Адрес: Россия, 197022, г. Санкт-Петербург, ул. Льва Толстого, 6–8 Тел.: (812) 338-62-62, E mail: xihmrx@gmail.com Статья поступила 18.12.17, принята к печати 20.06.18. Contact Information: Shcherbakov Alexander Aleksandrovich – anesthesiologist-reanimatologist of resuscitation and intensive care department, R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University Address: Россия, 197022, St. Petersburg, L. Tolstogo str., 6–8 Теl.: (812) 338-62-62, E mail: xihmrx@gmail.com Received on Dec. 18, 2017, submitted for publication on Jun. 20, 2018. © Коллектив авторов, 2017 DOI: 10.24110/0031-403X-2018-97-5-41-46 https://doi.org/10.24110/0031-403X-2018-97-5-41-46

The paper analyzes peripheral blood findings from 34 patients (276 tests) at different time points following high-dose polychemotherapy and autologous hemopoietic stem cell transplantation. Most patients had resistant disease. Blood samples were tested for 26 parameters including reticulocytes, reticulocyte and platelet indices. Ferritin, soluble transferring receptor contents, endogenous erythropoietin were measured. Most patients had anemia before high-dose chemotherapy identified as chronic anemia with high or normal ferritin levels and erythropoietin production not adequate to anemia degree. Testing for young platelet, reticulocyte forms and their indices was shown highly informative for prediction of hemopoiesis recovery start.

Aim. To evaluate the effectiveness of preventive and prophylactic post-transplantation therapy using azacitidine (5-AZA) in patients at high risk of post-transplantation relapse. Methods. 136 patients were included in the study performed by the pairwise comparison: 68 of them received 5-AZA after allo-HSCT and 68 patients were included in the historical control group. 5-AZA was prescribed for prophylactic or preventive purposes. The results were assessed according to the OS, RR, EFS, DUM, and relapse-free and GVHR-free survival. Results. 1-year OS was 76 % in the 5-AZA group (95% CI 60-84 %) and 44 % in the reference group (95% CI 33-55 %) (р = 0.001); 2-year OS was 63 % (95% CI 39-67 %) and 37 % (95% CI 26-48 %) (р = 0.007), respectively. The relapse rate (RR) in the 5-AZA group was 34 % (95% CI 22-46 %) during 1 year and 51 % (95% CI 38-64 %) in the reference group (р = 0.02). 1- and 2-year disease unrelated mortality (DUM) was similar: 5 % in the 5-AZA group (95% CI 0.1-14.0 %) and 25 % (95% CI 13-37 %) in the reference group (р = 0.005). 1-year EFS was 76 % in the 5-AZA group (95% CI 61-85 %) and 44 % in the reference group (95% CI 33-55 %) (р = 0.001); 2-year EFS was 63 % (95% CI 39-67 %) and 37 % (95% CI 2648 %) (р = 0.01), respectively. 1-year relapse-free and GVHR-free survival was 55 % in the 5-AZA group (95% CI 41-69 %) and 28 % in the reference group (95% CI 17-39 %) (р = 0.001); 2-year relapse-free and GVHR-free survival was 47 % (95% CI 32-62 %) and 27 % (95% CI 17-37 %) (р = 0.002), respectively. Conclusion. The use of 5-AZA for prophylactic and preventive purposes after allo-HSCT does not increase the risk of GVHR and DUM, does not suppress the GVL effect and can be used in combination with the donor lymphocyte infusion (DLI). The therapy with 5-AZA is safe during the early period after allo-HSCT. The drug does not suppress the GVL effect and can be used in high risk patients to prevent early post-transplantation relapse. The use of 5-AZA in combination with DLI does not increase the incidence of severe GVHR.

Aim. The aim was to evaluate the results of the allogeneic hematopoietic stem cells transplantation (allo-HSCT) in children and adults with the most prognostically unfavorable acute lymphoblastic leukemia (ALL) with t(4; 11)(q21; q23)/KMT2A-AFF1 translocation. Methods. We examined 21 patients (12 females, 9 males) aged from 3 months to 48 years (median 18.9 years). The analysis of prognostic factors of overall (OS) and eventfree survival (EFS) after allo-HSCT in patients of different age groups with various clinical, transplantation and cytogenetic characteristics was performed. Allo-HSCT from HLA-compatible related and unrelated donors, as well as haploidentical allo-HSCT were performed in 4, 9 and 8 patients of age groups < 1 year, 1-18 years, and >18 years, respectively. In 10 (48 %) patients, allo-HSCT was performed in the first remission, in 2 (10 %) patients in the second remission, and in 9 (43 %) patients during the disease relapse. Results. In 8 (38 %) patients, the only chromosomal disorder was the translocation t(4; 11)(q21; q23). Additional changes in chromosomes were found in 11 (52 %) patients. In 8 (38 %) of them, 3 or more chromosomal abnormalities in the karyotype were found. According to the results of a univariant analysis, the OS and EFS were significantly different in patients with allo-HSCT performed in the first remission and at other stages of ALL (in the second remission and in relapse: p < 0.001 in both cases), as well as in patients with or without 3 or more cytogenetic disorders in the karyotype (p = 0.04 in both cases). The multivariant analysis showed that the only independent prognostic factor affecting the OS and EFS in ALL patients with t(4; 11) was the allo-HSCT, including the haploidentical procedure, during the first complete hematological and molecular remission (p = 0.002 and p = 0.0004, respectively). Conclusion. ALL with t(4; 11)/KMT2A-AFF1 was as an absolute indication for allo-HSCT in first remission, including children of < 1 year age group. Satisfactory results can be obtained with the use of haploidentical transplantation from the parents. This approach eliminates the search in the registers completely HLA-compatible donor and facilitates the treatment procedure.

Background. Despite of modern methods of diagnosing, prevention and treatment, invasive fungal disease (IFD) remains actual problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data of IFD in adolescents and young adults (15–25 y.o.) after allo-HSCT are limited. The aim of the study was to estimate of incidence, etiology, clinical signs and outcome of IFD in adolescents and young adults recipients of allo-HSCT. Materials and methods. In retrospective single center study from Jan 2013 to Dec 2014 were included 80 pts after first allo-HSCT in the clinic of Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg. EORTC/MSG 2008 criteria for IFD diagnosis were used. “Active IFD” means IFD diagnosed just before HSCT. Results. Incidence of IFD before allo-HSCT was 18.8 % (n = 15): invasive aspregillosis (IA) (n = 11), invasive candidiasis (IC) (n = 3) and 1 patient had two IFD (IA + IC). Complete response to antifungal therapy was in 40 %, partial – 26.7 %, “active” IFD – 33.3 %. Secondary antifungal prophylaxis was made predominantly with voriconazole (80%). Patients without IFD before HSCT (n = 65) received primary antifungal prophylaxis predominantly with fluconazole (85 %). Cumulative incidence of IFD-events at 1 year after allo-HSCT was 15 %, at 2 years – 18.8 % including new cases of IFD (n = 14) and relapse of IFD (n = 1) after allo-HSCT with median day of oncet +43 (14–577). Incidence of IA was 15 %, IC – 2.5 %, pneumocystis pneumonia (PCP) – 1.25 %. IFD risk factors after allo-HSCT (< 0.05) were: age < 18 years, non-malignant diseases, active disease at the moment of HSCT, neutropenia grade IV more than 20 days, acute “graft-versus-host” disease. First-line therapy were: IA – voriconazole (58.3 %), IC – echinocandins (100 %), PP – co-trimoxazole (100 %). 12-weeks overall survival (OS) from day of IFD diagnosis after allo-HSCT was 93.3 %, IA – 91.7 %. All patients with IC and PCP alive. 100-days OS after allo-HSCT was 85 %, 2-year OS after allo-HSCT – 67.5 %. There was no difference in OS in patients with or without IFD before allo-HSCT. Conclusion . Incidence of IFD in adolescents and young adults before allo-HSCT was 18.8 %. Only one patient relapsed with IA after allo-HSCT. Incidence of IFD after allo-HSCT (1 year) was 15 %. The main IFD was invasive aspergillosis. 12-weeks overall survival from IFD diagnosis after allo-HSCT was 93.3 %. IFD before and after allo-HSCT did not impair the outcome of the transplantation in adolescents and young adults.

Aim. To evaluate the impact of additional chromosomal aberrations on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation. Methods. Twenty-five AML patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation (10 women and 15 men, aged from 2 to 58 years; median 20.2) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed. Results. The additional cytogenetic abnormalities were found in 13 (52 %) patients before the transplantation, at that, complex karyotype with three or more chromosomal abnormalities were registered in 9 (69 %) patients. The univariate analysis showed that OS and EFS after allo-HSCT differed in patients with different characteristics such as age (p = 0.03; p = 0.0006), clinical status at transplantation (p = 0.0002; p = 0,006), donor type (p = 0.0003; p = 0.002), the interval from diagnosis of leukemia to allo-HSCT (p = 0,008, for OS only), additional cytogenetic abnormalities (p = 0.03; p = 0.009) and complex karyotype (p = 0.004; p = 0.0003), respectively. In multivariate analysis, independent predictors of OS were donor type (p = 0.01), the interval from diagnosis of leukemia to allo-HSCT (p = 0.01), and additional cytogenetic abnormalities in karyotype (p = 0.04), as well as donor type (p = 0.04) and patient’s age (p = 0.004) for EFS. Conclusion. AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation is a heterogeneous disease. The prognosis in patients with the additional cytogenetic abnormalities, especially in those with the complex karyotype, is worse both after the standard chemotherapy (i.e. before allo-HSCT), and after allo-HSCT.

Background & Aims. So far there is no data presented on the effectiveness of prevention of the graft-versus-host reaction (GVH) using post-transplant cyclophosphamide (PTCy) prescribed after unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study is to evaluate the incidence of acute and chronic GVH, the transplantation-associated mortality rate, the event-free and overall survival rates, as well as the toxicity profile and the incidence of infectious complications in the study group using cyclophosphamide for GVH prevention; the other aim is to carry out a comparative analysis of the obtained results with the historical control group. Methods. 110 adult patients were enrolled in a clinical study to evaluate the effectiveness of GVH prevention, using PTCy (No. NCT02294552). In order to prevent GVH, the study group (PTCy group) received cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF). The historical control group (ATG group) consisted of 160 patients prescribed with a GVH prevention regimen including anti-thymocyte globulin (ATG), calcineurin inhibitors, and methotrexate or MMF. Peripheral blood stem cells were used as a source of the transplant. Results. The cumulative incidence of II-IV degree acute GVH (18.2 % vs. 40.4 %, respectively; p < 0.0001), III-IV degree GVH (4.5 % vs. 22.5 %, respectively; p < 0.0001), and chronic GVH (21.7 % vs. 40.6 %, respectively; p < 0.0001) was significantly lower in the PTCy group than in the ATG group. Prevention of GVH based on PTCy was associated with the reduction in transplant-associated mortality (12.7 % vs. 33.7 %, respectively; p = 0.003), increased overall survival (70.9 % vs. 44.4 %, respectively; p < 0.001), event-free survival (68.2 % vs. 38.1 %, respectively; p < 0.001) and GVH- and relapse-free survival rates (59.1 % vs. 16.3 %, respectively; p = 0.001). Prevention of GVH using PTCy (as compared to ATG) was less toxic, accompanied by a reduction in the incidence veno-occlusive disease (2.7 % vs. 10.9 %, respectively; p = 0.016), severe mucositis (69.5 % vs. 87.6 %, respectively; p < 0.001), and invasive mycosis (7.2 % vs. 29 %, respectively; p < 0.001). Conclusion. A combination of cyclophosphamide with tacrolimus and MMF is an effective regimen for GVH prevention in patients after allo-HSCT from an unrelated donor.

Aim. To evaluate the prognostic impact of the different cytogenetic characteristics, including the modal number, the number of chromosomal aberrations in a complex karyotype, and adverse chromosomal abnormalities (ACA) (-7/7q-, -5/5q-, -17/17p-, t(6; 9)(p22; q34)) on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hyperdiploid acute myeloid leukemia (H-AML). Methods. Forty seven H-AML patients (21 women and 26 men, aged from 1 to 58 years, median - 23.9 years) were examined. The analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed. Results. The modal number of chromosomes (MN) of 4748 was the most common one in the karyotype which was observed in 31 (66 %) patients. High hyperdiploidy with the modal number of 49-65 was identified in 13 (28 %) patients, near-triploid and near-tetraploid karyotypes were found in 3 (6 %) patients. Quantitative chromosomal abnormalities were nonrandom. Chromosome 8 (50 %), 21 (32 %), 13 (16 %) and 22 (16 %) trisomy was the most common one. Structural chromosomal abnormalities were detected in 22 (47 %) patients, at that, ACA were found in 7 (19 %) patients. In univariate analysis, the OS and EFS after allo-HSCT differed in patients with different clinical status (remission vs. active disease; p = 0.003 and p = 0.002, respectively), different chromosomal abnormalities in hyperdiploid karyotype (ACA- vs. ACA+; p = 0.001 and p = 0.03, respectively). An additional analysis of selected patients group with a structurally complex karyotype (n = 19) showed, that patients without ACA had a higher OS than patients with ACA (p = 0.03). In multivariate analysis, the disease status (relapse) at allo-HSCT was an independent predictor of decreased OS and EFS (p = 0.004 и p = 0.006, respectively), as well as the presence of the ACA (p = 0.002 only for OS). Conclusion. ACA were high-risk factors in H-AML patients received allo-HSCT. Therefore, the patients with formal criteria of a complex karyotype should not be automatically included in the cytogenetic unfavorable risk group.

Aim. To evaluate the prognostic significance of the complex karyotype including del(5q), -7, del(7q) abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. Forty-four AML patients with chromosome 5 and/or 7 abnormalities (22 women and 22 men, aged from 1.2 to 67 years, median 31.2 years) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed. Results. Prior to allo-HSCT, the complex karyotype (with three or more chromosomal abnormalities) was observed in 19 (43 %) patients, the monosomal karyotype was in 8 (18 %) patients. Univariate analysis demonstrated that OS and EFS differed in patients from different age groups (> 18 vs. < 18 years; p = 0.01 and p = 0.05, respectively), with different disease status at transplantation (1 remission vs. other clinical status; p = 0.1 and p = 0.008, respectively), with and without complex karyotype (СК- vs. CK+; p = 0.05 and p = 0.002, respectively), with and without monosomal karyotype (МК- vs. MK+; p = 0.009, only for EFS), and with different stem cells source (bone marrow vs. other source; p = 0.03 only for OS). Multivariate analysis confirmed that age of 18 years and more (p = 0.02 and p = 0.01, respectively), active disease at allo-HSCT (p = 0.04 and p = 0.005, respectively), complex karyotype (p = 0.04 и p = 0.0008, respectively) and stem cell source other than bone marrow (p = 0.02 only for OS) were independent predictors of OS and EFS deterioration. Conclusion. The study demonstrates that chromosome 5 and/or 7 abnormalities as a part of the complex karyotype is high-risk factor in AML patients undergoing allo-HSCT (unlike the monosomal karyotype), that requires the special therapeutic approach.