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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 1st or 2nd 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 1st complete clinical and hematologic remission (CCHR) and 5 (19.2 %) – in the 2nd CCHR; among the controls, there were 19 (70.4 %) cases of the 1st CCHR and 8 (29.6 %) cases of the 2nd 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+ × 106/kg) in the PTC group was 4.60 (1.7–10.9) × 106/kg, in the historical group – 6.60 (1.0–13.2) × 106/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.

The loss of a patient-specific HLA haplotype on the surface of the blast cell population is one of the ways a tumor can evade the immune surveillance of donor cells. This phenomenon is observed in approximately 30 % of relapses in patients with hematologic malignancies who underwent partially mismatched allogeneic hematopoietic stem cell transplantation (HSCT). In this study, for the first time, a large cohort of pediatric patients (n = 80) with relapsed acute myeloid (AML) or acute lymphoblastic (ALL) leukemia after allogeneic HSCT was analyzed with the help of the STR method (highlypolymorphic microsatellite marker analysis) using 6 HLA haplotype markers. 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. Loss of heterozygosity (LOH) was observed in 18 / 80 (22 %) relapsed patients with various types of acute leukemia: out of these, 8 / 44 (18 %) patients had B-cell ALL, 4 / 10 (40 %) patients – T-cell ALL and 6 / 25 (24 %) patients – AML. All relapses with LOH were observed in patients who had undergone haploidentical HSCT, and were found to occur later than relapses without loss of the HLA haplotype (median time to relapse: 8.8 months vs 6.2 months, p = 0.043). In the patients treated with haploidentical HSCT (n = 61), we assessed factors increasing the risk of LOH at relapse. The number of previous therapy lines in the patients with AML (n = 17) and acute or chronic graft-versus-host disease in the patients with ALL (n = 44) were associated with an increasedrisk of genetic loss of the HLA haplotype (p = 0.008 and p = 0.015 respectively). A relapse following the second allogeneic HSCT was associated with LOH in 4 / 5 (80 %) patients, p = 0.008. The prognosis of the patients with LOH was extremely poor. At a median follow-up of 6 months, the overall survival from relapse was 22 % in the LOH group and 37 % in the non-LOH group. The median overall survival was 4.5 months (95 % confidence interval 3–NA) and 10.3 months (95 % confidence interval 5.7–16.1) respectively, p = 0.063. Among the patients with LOH, the best survival rates were observed in those who had undergone a repeat allogeneic HSCT from a different donor. Thus, the analysis of LOH is an important tool for determining the prognosis and further treatment in pediatric patients with acute leukemias. We strongly recommend that this diagnostic test should be included into standard testing of patients after partially-mismatched allogeneic HSCT.

Introduction. Atypical teratoid/rhabdoid tumor (ATRT) of the central nervous system (CNS) belongs to the embryonic group, occurs mainly in children under 3 years of age and is characterized by an extremely aggressive clinical course and unfavorable outcome. However, there is not enough data about the heterogeneity of the clinical course of CNS ATRT and the role of clinical and therapeutic prognostic factors in patients under 1 year of age and 1–3 years of age.The aim of this study was to conduct a comparative evaluation of treatment results in children with CNS ATRT in the indicated age groups.Materials and methods. From 2008 till 2021 years 106 patients were included in this study. Each patient underwent a therapeutic program according to determined protocol (ATRT-2006, MUV-ATRT, EU-RHAB and individual variant). All patients were divided into 2 groups according to age: from 1 to 12 months – 41 patients, from 13 to 36 months – 65. Median of the age was 16 (9–23) months. These cohorts of patients (1–12 months and 13–36 months) were comparable in clinical and therapeutic characteristics depending on gender, localization of the primary tumor site, stage of the disease, extent of surgical resection, therapeutic protocol, number of patients, who underwent radiation therapy (RT), high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT), intrathecal/ intraventricular chemotherapy.Results. At the time of analysis 48 (45.3 %) patients were alive, 58 (54.7 %) patients died, of whom 52 (90 %) from disease progression and 6 (10 %) from therapeutic complications. One-year progression-free survival (PFS) in the group from 1 to 12 months was 32 %, 2-year – 18 %, 5-year – 18 %; one-year overall survival (OS) – 53 %, 2-year – 29 %, 5-year – 25 % with a median follow-up 8 and 13 months respectively. One-year PFS in the group from 13 to 36 months was 61 %, 2-year – 36 %, 5-year – 33 %; one-year OS – 86 %, 2-year – 67 %, 5-year – 49 % with a median follow-up 19 and 38 months respectively. In our study we identified the main predictors of the PFS and OS improvement in patients with ATRT CNS of each age group. In the 1–12 month group, these factors were: absence of metastatic involvement, MUV-ATRT therapeutic protocol, RT and HDCT with auto-HSCT; in the 13–36 months group: gross total/near gross total resection of the primary tumor cite, ATRT-2006 therapeutic protocol and RT.Conclusion. Despite the fact, that the presence of a diagnosis of ATRT CNS in children under 3 years of age is usually associated with a high risk of disease progression and recurrence, the results of our study demonstrate the heterogeneity of the clinical and therapeutic profile in this age group of patients.

Anaplastic large cell lymphoma (ALCL) expressing the anaplastic lymphoma kinase (ALK) (ALK+ ALCL) is a rare type of lymphoma which comprises 10-15% of all non-Hodgkin lymphomas in children and 2–3% in young adults. Relapsed/refractory disease occurs even more rarely (25–40% of all cases). There is as yet no standard treatment for relapsed/refractory ALK+ ALCL. Patients with ALK+ ALCL usually present at advanced stages of the disease with extranodal involvement (skin, soft tissues, bones, lungs, liver, spleen and bone marrow) and B symptoms. ALK-positive ALCL affects males more often than females. There are two morphological variants: the common type (65% of cases) and the non-common type which is associated with a poorer prognosis. ALK+ ALCLs are often associated with t(2;5) and t(1;2), resulting in the formation of the NPM-ALK and the TPM3-ALK fusion proteins, respectively. Data about the treatment of relapsed/refractory ALK+ ALCL are limited. Earlier, targeted therapies (brentuximab vedotin (BV), ALK inhibitors) and risk-adapted chemotherapy followed by hematopoietic stem cell transplantation (HSCT) for remission consolidation were shown to be highly effective. A total of 15 patients with relapsed/refractory ALK+ ALCL were treated at the R.M. Gorbacheva Research Institute starting from 2002. Fourteen (93%) patients had ALK-positive ALCL of common morphology and one (7%) patient had the non-common variant (histiocytic). The study was approved by the Independent Ethics Committee and the Scientific Council of the Pavlov University. The expression of CD3 on tumor cells was assessed (CD3 positive: n = 4 (27%), CD3 negative: n = 8 (53%), no data: n = 3 (20%). The median age at the diagnosis was 26 years (11 months– 37 years). The median follow-up from the diagnosis was 9 years (1–19 years). Nine (60%) patients were aged > 18 years and six (40%) patients were aged < 18 years. There were 10 (67%) males and 5 (33%) females. At onset, 2 (13%) patients were diagnosed with early-stage disease (stage II), while the others were diagnosed with advanced-stage disease: 2 (13%) patients had stage III disease and 11 (74%) had stage IV disease. Staging was performed according to the St. Jude staging system (in children) and the Ann Arbour staging classification (in adults). Thirteen (86%) patients had extranodal involvement. Four (27%) patients had refractory disease (progression within the first three months or the absence of complete remission after the first-line treatment) and the rest 11 (73%) patients had recurrent ALK-positive ALCL. Six patients developed early relapse (< 12 months after remission was achieved); 5 patients had late relapse (after > 12 months of remission); local (1 site) and systemic relapses were diagnosed in 7 and 4 patients, respectively. Our patients received from 2 to 7 lines of treatment (the median is 4). In the first line of therapy, the patients were treated according to NHL-BFM based regimens (n = 9; 60%), the CHOP (n = 5; 33%), and the HyperCVAD (n = 1; 7%) protocols. In the second line of therapy, 8 (53%) patients were treated according to NHL-BFM based regimens; 2 (13%) patients were treated with GDP; 1 (7%) patient received DHAP chemotherapy; 1 (7%) patient received a combination of methotrexate and vinblastine (MTX + V); 1 (7%) patient received bendamustine as a single agent. Two (13%) patients were treated with chemotherapy in combination with targeted drugs (GDP + BV, n = 1; NHL-BFM + crizotinib, n = 1). As a third or subsequent line of treatment, the patients received a variety of chemotherapy regimens (n = 5; 33%) and chemotherapy in combination with targeted drugs (n = 10; 67%). Five (33%) patients underwent ALK-inhibitor therapy (crizotinib (n = 4) and ceritinib (n = 1)). Seven (46%) patients were treated with BV (BV as a single agent (n = 4) and BV + chemotherapy (n = 3)). The median number of treatment lines before autologous HSCT (auto-HSCT) and allogeneic HSCT (allo-HSCT) was 2 (2–3) and 3 (3–4), respectively. Auto-HSCT was carried out in 11 (73%) cases. Nine (60%) patients underwent allo-HSCT (from a matched unrelated donor (n = 6), from a matched related donor (n = 2), and from a haploidentical donor (n = 1)). One patient received NK cells from a haploidentical donor as maintenance. In 5 (33%) cases, alloHSCT was carried out following auto-HSCT. The conditioning regimens (CR) used for auto-HSCT included BEAM (carmustine – 300 mg/m2, etoposide – 800 mg/m2, Cytosar – 1600 mg/m2, melphalan – 140 mg/m2) – in 5 (45%) patients; BeEAM (bendamustine – 320 mg/m2, etoposide – 800 mg/m2, Cytosar – 1600 mg/m2, melphalan – 140 mg/m2) – in 5 (45%) patients; and BuCy (Cyclophosphan – 100 mg/kg, busulfan – 14 mg/kg) – in 1 (10%) case. Seven (78%) patients undergoing allo-HSCT received the FluBenda conditioning regimen (fludarabine – 90–150 mg/m2, bendamustine – 390 mg/m2) and post-transplant Cyclophosphan and calcineurin inhibitors for the prevention of graft-versus-host disease (GVHD) (n = 7; 78%); one (11%) patient received the FluMel regimen (fludarabine – 150 mg/m2, melphalan – 140 mg/m2) and CsA/MTX (Cyclosporin А, methotrexate) for GVHD prevention; and in 1 case (11%) data on the RC and GVHD prophylaxis were missing. Overall response to the second line of treatment was achieved in 10 (67%) patients, with complete response observed in 7 (47%) cases, and partial response –in 3 (20%) cases. Five out of the 7 patients treated with BV during different lines of therapy managed to achieve complete response. Four out of the 5 patients who had undergone treatment with ALK inhibitors, demonstrated complete response. The 10-year overall survival (OS) rate of the study patients reached 90% (95% confidence interval (CI) 47–99). The 10-year progression-free survival (PFS) rate after the second line of treatment was 39% (95% CI 13–64). The 10-year OS and PFS rates after auto-HSCT were 100% and 35% (95% CI 8–64) respectively. The 5-year OS following allo-HSCT was 85% (95% CI 33–98), while PFS was 60% (95% CI 19–85). Four out of the 11 patients who had undergone auto-HSCT relapsed, and 2 patients progressed. Median time to relapse/progression was 8 (6–27) months. Three out of the 9 patients who had been treated with allo-HSCT ended up relapsing (median time: 8 (6–17) months). Two patients achieved repeated remission (in one case, it was the result of treatment with ceritinib, while in the other case it became possible after the resection of the lesion, radiotherapy and prescription of crizotinib), and 1 study patient died as a result of disease progression 17 months after allo-HSCT. The 6 patients who had achieved complete remission before undergoing allo-HSCT, are still in CR. Five out of the 9 patients developed grade I–II acute GVHD with skin involvement but did not show any signs of chronic GVHD. The observed complications of chemotherapy and auto-HSCT were standard and manageable and were not the focus of attention in this study. Taking into account the high probability of developing resistance to ALK inhibitors and the high risk of relapse after treatment with BV, targeted therapy should be used to prepare patients for HSCT. The use of ALK inhibitors and BV in our study led to repeated remission in 80% and 71% patients respectively. It was demonstrated that in the majority of cases even heavily pretreated patients with ALK+ ALCL can be cured (which is not the case with other non-Hodgkin lymphomas), especially if allogenic HSCT (allo-HSCT) is carried out. Still, we think that auto-HSCT can also be considered for remission consolidation since OS rates following auto-HSCT and allo-HSCT are comparable (100% and 85%). Moreover, auto-HSCT can also be a valid option in the absence of a fully matched donor, i.e. when only an alternative (haploidentical or partially matched) donor is available, since the use of haploidentical HSCT in ALCL patients has not been studied well enough yet. Further research on the matter is warranted. It was demonstrated that a non-myeloablative conditioning regimen before allo-HSCT (FluBenda) could be opted for in patients with relapsed/refractory ALK+ ALCL and that it was similarly effective as myeloablative RC when compared with a historical control group. Disease status before HSCT was proven to have a statistically significant influence on PFS (the best prognosis was associated with complete remission). At the same time, other factors did not impact the prognosis. This may be explained by the relatively small number of patients included in the study. Relapsed/refractory ALK+ ALCL is a disease with a relatively good prognosis even in heavily pretreated patients. Targeted therapy is a very important and effective step in preparation for HSCT. Allo-HSCT is more effective than auto-HSCT but the latter can also be considered a valid therapeutic option.

The majority of patients with Hodgkin lymphoma (HL) are cured, which represents one of the best cure rates in oncology. However, the prognosis is not as favorable in case of relapsed or refractory (RR) disease. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective way to consolidate remission in patients with RR HL. Despite the many years of experience and the availability of results of randomized trials confirming the efficacy of high-dose chemotherapy in adults, the role of auto-HSCT in children with HL has not been studied as extensively, and there are only a limited number of publications on the subject. As is the case with the majority of other pediatric tumors, RR HL is a rare entity, which is why it is so difficult to study it. Here we share the experience of the R. M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation in auto-HSCT in children and adolescents with HL. The study was approved by an Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint-Petersburg State Medical University. We included 54 patients with RR HL who had undergone auto-HSCT during the period from 2007 to 2021. Refractory disease (n = 29; 54 %) was diagnosed in case of HL progression either during first-line therapy or in the first 3 months after the completion of the treatment. Relapsed disease was diagnosed in 25 (46 %) children. Early HL relapse (< 12 months since the start of therapy) was evident in 18 (72 %) patients, while late HL relapse (≥ 12 months since the start of therapy) occurred in 7 (28 %) children. The median number of lines of therapy before auto-HSCT was 3 (1–6). The first line of treatment was chemotherapy in accordance with the GPOH-HD (n = 27; 50 %), BEACOPP (n = 19; 35 %), or other protocols (n = 8; 15 %); the second line involved the use of IEP/ABVD (n = 14; 27 %), DHAP (n = 12; 23%), ICE (n = 13; 25 %), or other combinations (n = 13; 25%); and third-line treatment consisted of DHAP (n = 9; 29 %), a combination of brentuximab vedotin and bendamustine (n = 8; 26%), immune checkpoint inhibitors (ICIs) (n = 7; 22.5 %) or other regimens (n = 7; 22.5 %). ICIs were used for remission induction prior to auto-HSCT in 14 (26 %) patients. Response was assessed using the Lugano classification. Status before transplantation: complete remission (CR) – 21 (39 %) patients, partial remission (PR) – 30 (56 %), disease stabilization – 2 (3.5 %), disease progression – 1 (1.5 %). The BEAM conditioning regimen was used in 17 (31 %) patients, and the BeEAM regimen – in 32 (59 %) patients. The 3-, 5- and 10-year overall survival (OS) was 88% (95 % confidence interval (CI) 74–95), 80% (95 % CI 62–90) and 63% (95 % CI 34–81) respectively. The 10-year progression-free survival (PFS) was 46% (95 % CI 24–65). The median follow-up was 3.3 (0.1–12.3) years. The long-term PFS in children with CR and PR was 72% (95 % CI 41–89) and 33 % (95 % CI 8–61) respectively (p = 0.067). A total of 9 (16.7 %) patients died during follow-up. The main cause of death was progressive HL (n = 6), while some patients died in the early post-transplant period due to infections (n = 3; 5.6 %). The median time to relapse or progression after auto-HSCT was 6 (1–77) months. Out of 17 (31 %) patients with relapsed or progressive HL after auto-HSCT, 9 (53 %) children are alive at a median follow-up of 2.3 (0.7–9) years. Considering that our study included patients who had been more extensively pre-treated (the median number of lines of therapy – 3) than patients in the majority of other studies (the median number of lines of therapy – 2), it can be assumed that our results are superior to historical data. The improvement of transplantation outcomes observed over time can be attributed to better supportive treatment and probably, to the use of immunotherapy. According to the Center for International Blood and Marrow Transplant Research (CIBMTR), it is crucially important that long-term survival in children with RR HL be monitored closely since it can be drastically different from results obtained during the first years of follow-up - due to late relapses and complications of the received treatment. The 10-year survival rates show that the RR HL problem is yet to be resolved. With the help of auto-HSCT, approximately half of children and adolescents with RR HL can be cured. One of the most important favorable prognostic factors in these patients is the achievement of CR before transplantation. The use of immunotherapy for remission induction before auto-HSCT is also promising.

Withdrawal of radiotherapy in patients with brain tumors under four years decreases chance for cure. AutoHSCT in a series of pilot studies demonstrated a potential to improve outcomes in these patients. The study included 50 patients with median age of 39 months (7-53). Medulloblastoma (n = 28, 56%), ETMR (n = 9, 18%) and other histological types (n = 13, 26%) were most commonly diagnosed. Forty two patients (84%) received tandem autoHSCT by HIT-MED protocol, and single autoHSCT was performed in eight children (16%). Adjuvant radiotherapy was administered in 25 (50%) children and treatment of relapse included radiotherapy in 6 (12%). Median follow-up was 39.6 months (6-121). Long-term CIR was 37%, and TRM - 6%. Five-year OS was 71% in medulloblastoma, 37% in ETMR and in other tumors - 51% (p = 0.07). Irradiation-free OS at 5 years for children with medulloblastoma was 24%. For the whole cohort of CNS tumors, independently of histology, OS and PFS at five years were 60% and 46%, respectively Young children with medulloblastoma, following tandem autoHSCT, demonstrate OS comparable to older children. Patients with other histological types demonstrate suboptimal long-term survival rates after autoHSCT and one should assess whether these patients benefit from autoHSCT.

The aim of the research. Evaluation of the structure of viral hepatitis in patients with oncohaematological diseases and activity of ALT and AST during various methods of treatment of the main disease.Materials and methods. Retrospective analysis of data from 2000 patients treated during 2001–2014 in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation Pavlov of the First Saint Petersburg State Medical University was carried out. The dynamics of cytolytic enzymes during therapy (polychemotherapy, transplantation of hematopoietic stem cells, symptomatic) of oncohematological diseases was evaluated between the patients with concomitant chronic viral hepatitis (N=175) and without liver pathology (N=203). Analysis was performed with SAS software. Results. Over a 10-year follow-up period, 9% of the oncohematological patients of the specialized center identified markers of hemocontact viral hepatitis. The results of the study showed that in patients with concomitant viral hepatitis, in contrast to a group without hepatitis the activity of ALT and AST significantly increased compared to baseline values after the treatment of hematological malignancy. It was twofold increase of the activity of enzymes after transplantation of hematopoietic stem cells and 3–4- fold incease after courses of polychemotherapy. In patients without viral hepatitis, changes in enzyme activity after such therapy were not observed. Summary. Thus, the associated effect of concomitant viral hepatitis and toxic effects of treatment methods with the use of polychemotherapy and transplantation of hematopoietic stem cells was proven on the development of cytolytic syndrome in oncohematological patients.

Introduction. The question of the most adequate treatment strategy of AML in cases when it is impossible to perform allogeneic HSCT because of any reason still remains open. The aim of this study was to assess the long-term survival of patients with AML who received chemotherapy (CT) or autologous HSCT as consolidation in the first remission of the disease. It was included 135 patients aged 18 to 67 years, with a verified diagnosis of AML (except FAB M3) in the study. Of these, 100 patients received only CT, 35 patients received consolidation with autologous bone marrow transplantation. Patients who achieved remission after completion of induction CT courses received one of three treatment options as consolidation: 1) chemotherapy of standard-intensity (sCT), 2) high-dose chemotherapy (HDCT), 3) autologous HSCT (autoHSCT) conducted after 1–2 courses of high-dose CT. Adverse prognostic factors were identified as: age over 40 years, hyperleucocytosis more than 50,0 × 10 9/L and unfavorable cytogenetic and molecular-biological risk group. Materials and methods. Depending on the number of prognostic factors at the onset of disease relapse-free survival (RFS) was 47 % in their absence, 45 % in the presence of 1 factor, in the presence of 2 factors – 14 % (p = 0,000), regardless of the variant of consolidation therapy (sCT, HDCT, autoHSCT). A high level of white blood cells adversely affects OS (38 % vs. 22 %) and increases the frequency of relapse (52 % vs. 69 %) when performing only CT (sCT and HDCT). At initial white blood cells level more than 50,0 × 10 9/L the 5-year OS was 60 % when performing both autoHSCT and HDCT. Performance of autoHSCT at failure to achieve remission after the 1st induction course CT is associated with the best 2-year OS (62 % vs. 35 %, p = 0,05), EFS (50 % vs. 22 %, p = 0,05) and RFS (50 % vs. 37 %, p = 0,05) in comparison with HDCT and sCT. In favorable cytogenetic risk group 5-year RFS was 80 % when performing autoHSCT and 67 % when performing HDCT; the 5-year OS was 80 % regardless of consolidation therapy option. Conclusion. AutoHSCT is the preferred consolidation option in favorable risk group patients, and after failure to achieve remission after the 1st CT course.

Osteopetrosis is a group of rare hereditary diseases, the general structural manifestation of which is the excessive volume of bone tissue due to violation of osteoclastic resorption. The only way to treat this group of patients so far remains transplantation of hematopoietic stem cells, but the degree of its effectiveness largely depends on the severity of morphological changes in the hematopoietic microenvironment in the bone marrow. In this regard, a comprehensive clinical and morphological analysis, in conjunction with the results of transplantation can help in determining the prognosis of the disease depending on the genetic type of osteopetrosis. The material for the studies were biopsies and smears of bone marrow of patients with osteopetrosis, who were received at the R. Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation from the republics of Chuvashia and Mari El for carrying out transplantation of hematopoietic stem cells. The histological preparations were stained with hematoxylin and eosin, azur by Romanovsky and by Van Gieson. Bone marrow smears were stained by Romanovsky-Giemsa. The presence of the mutation c.807 + 5G>A in the gene TCIRG1 in patients with autosomal recessive osteopetrosis causes a complete loss of osteoclastic resorption, which is accompanied by pronounced early structural changes in the hematopoietic microenvironment already at the time of diagnosis. This is manifested by an excessive amount of lamellar bone at the same time as the almost complete obliteration of the medullar lacunae, as well as fibrosis of the bone marrow stroma. A common morphological phenomenon among this group of patients is the presence in the bone marrow of an excessive number of osteoclast differentiation cells without the formation of resorption lacunae. This causes a complete suppression of hemopoiesis, which clinically manifests cytopenia and the formation of foci of extramedullary hematopoiesis. Such pronounced structural changes in the hematopoietic microenvironment result in a high risk of primary graft failure during after transplantation of bone marrow hematopoietic stem cells, the effectiveness of which decreases as the child's age increases. Early development of pronounced structural changes in the hematopoietic microenvironment in patients with TCIRG1-mediated osteopetrosis determines the need for diagnosis and transplantation as soon as possible after birth.

Introduction. AB0-incompatibility in different types of allogeneic hematopoietic stem cell transplantation (HSCT) may be an additional aggravating factor for the development of immunological complications and decrease treatment efficacy. Materials and methods. From May 1999 to December 2015 in R.M. Gorbacheva Memorial Research Institute for Children Oncology, Hematology and Transplantation 1131 patients with malignancies and hereditary diseases were included to the study, which were performed 1428 allogeneic HSCT: allogeneic unrelated – 814 (57.0 %), allogeneic related – 344 (24.1 %), haploidentical – 267 (18.7 %), umbilical cord blood in 3 patients (0.2 %). Age was 0–76 years, median – 25 years. Results. In 54.6 % of cases (n = 780) АВ0-incompatibility was determined: major – 37.8 % (n = 295); minor – 45.4 % (n = 354); combined – 16.8 % (n = 131). АВ0-incompatibility in allogeneic HSCT did not influence overall survival (p = 0.56), frequency of acute graftversus-host disease (GVHD) (p = 0.2). There was an increased frequency of acute GVHD in combination with reduced intensity conditioning regimens and АВ0-incompatibility (30.8 %) compared with myeloablative regimens (15.3 %; p = 0.002). Conclusion. The presence of АВ0-incompatibility is not a limiting factor to perform allogeneic HSCT, however, it demands high quality prophylaxis and sophisticated transfusion therapy to prevent immune complications.

Pathogenesis of acute leukemia is associated with the presence of genetic and functional aberrations in hematopoietic stem cells. However, as one of the possible factors contributing to the progression of disease could be regarded as the pull of the stromal cells of bone marrow. In this paper we evaluated the major functional characteristics of stromal cells: proliferative activity, hematopoiesis supportive and differentiation ability, as well as analysis of the expression of adhesion molecules. Stromal cells derived from acute leukemia patients in comparison with healthy donors are characterized by a high proliferative activity and a pronounced ability to osteogenic and adipogenic differentiation with prominent expression of hematopoietic stem cells homing mediating molecules.

A total of 115 children (median age 10.5 years, range 2-17) with Ewing sarcoma family tumors (ESFT) received therapy in N.N. Petrov Institute of Oncology pediatric department from April 1985 till August 2013. These patients were divided into two groups depending on treatment tactics used: patients treated according to modified T9 protocol (n = 64) and patients treated according to EICESS-92 or Euro-Ewing 99 regimens (n = 51). Twenty four patients from the second group with adverse prognostic factors received high-dose chemotherapy with autologous stem cell transplantation. All patients received surgical treatment and/or irradiation for primary tumor local control. Five-year overall and disease-free survival was 39% and 37,9% in the first group. In the second group these values were significantly higher; 55% and 39.5%, accordingly (p = 0.03 and 0.25). All patients from the first group with primary metastatic ESFT died of disease progression, while in the second group OS and DFS reached 45.8% and 28.9%, accordingly. There was a statistically significant correlation between local relapse rate and irradiation dose biological equivalent (in TDF units). The local relapse cumulative rate was minimal (12,6%) in patients receiving 80 TDF.

It is well-known that stromal cells have a crucial role in the regulation of hematopoiesis and engraftment [1]. Stromal cell studies became even more attractive after the c-kit ligand (stem cell factor) was discovered [2,3]. Data dealing with the biological properties of stromal cells in malignant hematological disorders are still scarce, however. The aim of this study is to evaluate the influence of bone marrow fibroblastand stormal cell-conditioned medium (CM of patients with acute leukemia (AL) on the proliferation and differentiation of normal and leukemic cells with respect to the development of potential diagnostic and prognostic markers.

Multiple myeloma (MM) is a malignant clonal B-lymphoproliferative disease. Survival ranges from a few months to many years [7]. The determination of prognosis for the disease’s course is important in therapeutic choice. At least two factors determine the course of MM: 1) the biology of myeloma cells and 2) the interrelation of malignant cells and host organism.