In children with acute lymphoblastic leukemia (ALL), relapse is still the leading cause of treatment failure occurring in 10–15% of cases. Overall survival after relapse plateaus at 50–60%, whereas event-free survival after second and third relapse is approximately 25% and 15%, respectively. The introduction of new immunotherapeutic agents such as blinatumomab (a bispecific T-cell engager), inotuzumab ozogamicin (InO; a CD22 + monoclonal antibody) and a chimeric antigen T-cell receptor targeted to CD19 + can significantly increase the effectiveness of treatment for relapsed ALL and help patients achieve remission faster and thus shorten the time to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the toxicity of these novel agents and their impact on the results of allo-HSCT are still to be investigated. Our study included 55 patients with refractory B-cell ALL aged from 3 to 17 years (the median age was 10 years). The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. The patients were divided into two groups based on whether they received inotuzumab ozogamicin or not: InO+ group ( n = 24; 43.6%) and InO– group ( n = 31; 56.4%). The majority of the patients underwent haploidentical HSCT ( n = 53; 96.4%); 1 (1.8%) patient received HSCT from a matched related donor, and 1 (1.8%) from a matched unrelated donor. Conditioning regimens before allo-HSCT included: myeloablative conditioning ( n = 20; 36.4%), reduced toxicity myeloablative conditioning ( n = 5; 9.1%), and reduced intensity conditioning ( n = 30; 54.5%). Acute graft-versus-host disease prophylaxis with post-transplant cyclophosphamide was given to 49 (87.7%) recipients; 6 (12.3%) patients received seroprophylaxis. Basic combined immunosuppressive therapy consisting of a calcineurin inhibitor and an mTOR inhibitor was used in 35 (63.6%) cases, and single m-TOR inhibitor treatment was administered to 20 (36.4%) patients. In the InO+ group, 21 (87.5%) patients achieved complete remission with incomplete hematologic recovery before allo-HSCT: 5 (23.8%) patients had minimal residual disease (MRD), and 16 (76.2%) patients were MRD negative. In the InO– group, remission with incomplete hematologic recovery before allo-HSCT was achieved in 15 (48.4%) patients: 3 (9.7%) cases were MRD positive and 12 (38.7%) were MRD negative ( p = 0.003). All the patients underwent allo-HSCT, regardless of response to prior therapy. Engraftment was achieved in the InO+ group in 20 (83.3%) children in a median of 22 days (D+22) and in the InO– group in 25 (80.6%) children in a median of 19 days (D+19). Relapse was observed in 11 (55%) patients in the InO+ group and in 15 (60%) patients in the InO– group at a median of 164 days and 203 days post-transplant, respectively ( p = n. s.). In the InO+ group, 5 (31.25%) out of 16 patients in complete remission with incomplete hematologic recovery and negative MRD status relapsed after allo-HSCT within a median of 105 days (D+58 – D+169). In the InO–, 6 (50%) out of 12 patients in complete remission with incomplete hematologic recovery and negative MRD status relapsed within a median of 296 days (D+108 – D+929). Due to the small number of patients in the groups, a correlation and regression analysis showed a weak correlation between the use of InO before allo-HSCT and the occurrence of post-transplant relapse (Pearson's contingency coefficient was 0.178). Loss of the HLA haplotype at relapse was found in 1 (4.2%) patient from the InO+ group and in 2 (6.5%) patients from the InO– group ( p = n. s.). Transplant-associated thrombotic microangiopathy was diagnosed in 6 (25%) recipients in the InO+ group and in 3 (9.7%) recipients in the InO– group. Eight (32%) patients in the InO+ group and 3 (9.7%) patients in the InO– group had clinical manifestations of sinusoidal obstruction syndrome. Our study suggests the effectiveness of inotuzumab ozogamicin for the treatment of relapsed B-ALL in children before allo-HSCT. Patients with large tumor burden and high expression of CD22 + would benefit the most from therapy with InO. The application of reduced intensity conditioning regimen after CD22 + directed monoclonal antibody therapy significantly improves the overall survival rates by reducing early transplant-related mortality and makes it possible to use adoptive immunotherapy as a next line of treatment. Current allo-HSCT protocols and approaches to acute graft-versus-host disease prevention help control the development of severe complications in the early post-transplant period. Our study showed that adoptive immunotherapy via donor lymphocyte infusions can be applied in patients treated with InO who experience loss of the HLA haplotype at relapse after allo-HSCT.

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.

Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive myeloproliferative/myelodysplastic neoplasm of early childhood characterized by activation of the Ras signaling pathway. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only proven curative treatment for JMML. However, the 5-year overall survival is about 52–64%. In this work, we analyzed 4 clinical cases of patients with relapses of JMML with loss of heterozygosity in HLA (LoH) after allo-HSCT. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications. Two patients received a second allo-HSCT from an alternative donor, two patients – from the same donor. A positive result in the form of a durable remission was observed in one patient who underwent a second allo-HSCT from an alternative donor and restored HLA genetic heterozygosity. At the same time, immunotherapy with infusions of donor lymphocytes led to the development of graft-versus-host disease without potentiating the antileukemic effect. Thus, a second allo-HSCT from an alternative donor for the treatment of relapsed JMML with HLA LoH is necessary to restore the “graft-versus-JMML” response. 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.

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.

Pleuropulmonary blastoma (PPB) is a very rare tumor of childhood that arises from the mesenchyme of the lung and is associated Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. Despite intensified therapy protocols, infant ALL remains a difficult-to-treat disease, with a high relapse rate. Allogeneic bone marrow transplantation is the only curative method aimed to curing the disease. Over the last decades, donor lymphocyte infusion (DLI) has been used as a salvage therapy after post-transplant relapses in B-ALL patients with a proven antileukemic effect. The combination of blinatumomab and DLI is a promising immunoadoptive therapy for resistant ALL based on the induction of “graft versus leukemia” effect by activating donor T-lymphocytes. We analyzed the results of combined immunoadoptive therapy with a bispecific T-cell activator blinatumomab and DLI in 3 infants with ALL, as well as the outcome of monotherapy with a bispecific T-cell activator in one infant. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. All infants initially had the KMT2A gene rearrangement and were classified as high-risk. The indication for immunoadoptive therapy was an early combined relapse of the disease after haploidentical hematopoietic stem cell transplantation in one patient and minimal residual disease (MRD) in three patients. All patients achieved long term hematological remission of the disease, 3 (75%) patients – MRD negative remission. The median duration of bone marrow response was 24 (8–63) months. One patient developed a bone marrow relapse in 8 months after therapy, two patients developed isolated extramedullary relapse. We did not see toxic complications and induction of graft-versus-host disease during immunoadoptive therapy. At the time of the follow up, all patients are alive, three remains in lasting hematological remission.

The study assessed the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 34 patients with cytogenetically verified variants of myelodysplastic syndrome (MDS) with trisomy 8 and/or monosomy 7, who were treated at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation from 2013 to 2020. Both adult and pediatric MDS were analyzed without excluding the variants with two additional chromosomal abnormalities or complex karyotype. The study revealed that а) allo-HSCT should be performed in the treatment of both MDS variants; b) the outcomes of trisomy 8 treatment appeared to be better; c) children with monosomy 7 showed a higher rate of toxic complications in allo-HSCT.

To improve the results of treatment of severe hemophilia in children, the efficiency and safety of the use of venous catheter ports in patients of this group has been analyzed. The problem of optimizing vascular access in hemophilia, especially young patients, remains relevant, despite the emergence of drugs with a subcutaneous route of administration. In global clinical practice, implantable permanent venous access devices (IVAD) have been successfully used for a long time to initiate preventive therapy or to conduct immune tolerance therapy when detecting inhibitor to coagulation factor VIII as early as possible. In Russia, this experience is still local and not reflected in the literature. Materials and methods of research: a single-center retrospective uncontrolled non-randomized study was performed. In a total of 19 patients (100% boys) between the age of 1 and 8 years (median 2 years [1; 6]) have been installed 21 IVADs. The observation period ranged from 200 to 1,897 days, with a total number of 17,484 catheter days in the group. Results: a statistically significant decrease in the number of hemorrhages requiring treatment per year (p<0,001) has been observed in the general group of patients following the implantation of IVAD and the optimum treatment. The incidence of infectious complications was 0,22 per 1000 catheter days with no other complications recorded. Conclusion: the results of the presented case report demonstrate that the use of a port-type IVAD to ensure adequate vascular access in young children with severe hemophilia with a high degree of safety significantly increases the effectiveness of substitution/hemostatic therapy.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III–IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57–89%) in acute GVHD and 81% (95% CI 67–92%) in chronic. Overall survival was 59% (95% CI 49–74%) in acute group and 85% (95% CI 70–93%). The major risk factors for lower survival were grade III–IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III–IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a hereditary storage disease caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase. Enzyme replacement therapy may extend the lifespan of affected patients by 6–12 years but the only currently available radical treatment option is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives: We aim to evaluate the influence of conditioning regimens of various intensities and “graft versus host” disease (GvHD) prophylaxis with anti-thymocyte globulin and post-transplant Cyclophosphamide (PTCy) on overall (OS) and event-free (EFS) survival, the incidence of GvHD, the normalization of alpha-L-iduronidase and glycosaminoglycan (GAG) levels over time as well as cardiovascular and cognitive recovery following allo-HSCT. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. We included 28 patients with MPS IH who had received allo-HSCT at the clinic at the R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation. The five-year OS was 89%, the EFS – 57%. The use of myeloablative conditioning regimens and allo-HSCT within 12 months of diagnosis improve EFS in affected patients. The cumulative incidence of grade II–IV acute GvHD and grade III–IV acute GvHD was 43% and 18% respectively. The use of PTCy results in a significantly lower incidence of this complication (69% vs 33%, p = 0.013). After allo-HSCT, normal alpha-L-iduronidase levels and urinary GAG excretion were achieved in cases where graft function was normal. Allo-HSCT is an effective treatment for patients with MPS IH. Myeloablative conditioning regimens are the preferred treatment modality for this group of patients but in cases of comorbidities or poor physical status at the time of allo-HSCT, conditioning regimens with reduced intensity may be opted for instead. PTCy may be used for GVHD prevention in patients with MPS IH without increasing the risk of cardiac toxicity.

Transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is an effective treatment method for non-malignant diseases and inherited disorders. Development of acute GVHD is a negative factor for outcomes. Using «novel» strategies for drug prophylaxis, such as posttransplant cyclophosphamide (PtCy) allows to decrease the GVHD risk. The aim of this study: to assess efficiency of PtCy as a prophylaxis aGVHDin the patients with non-malignant diseases of hematopoiesis and inherited syndromes. 97 patients with non-malignant blood disorders and metabolic diseases received 118 underwent allo-HSCT at the R. Gorbacheva Memorial Institute of Children Oncology and Transplantation. The aGVHD prophylaxis in 89 cases was performed by a standard schedule (with calcineurin inhibitors). 29 patients were treated according to PtCy regimen, at a dose of 50 mg/kg at days +3, +4. Cumulative incidence (CI) of aGVHD comprised 32%. Patients treated with PtCy exhibited lower rates of this condition compared to the group with standard prophylaxis schedule (26 vs 47%, р = 0.05). CI of skin aGVHD was also less common in the PtCy group (23 vs 45%, р = 0.046); gastrointestinal aGVHD was observed at equal rates in the both groups. Stem cell engraftment after nonmyeloablative conditioning in HSCT patients with subsequent PtCy administration proved to be sufficiently weaker compared to other patients (86 vs 50%, р = 0.004). Conclusions: aGVHD prophylaxis based on posttransplant PtCy is an efficient method which may decrease aGVHD risk. However, one should take into account a higher non-engraftment rate as a potential hazard of HSCT when using non-myeloablative conditioning regimens and PtCy-based GVHD prophylaxis.

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare and still poorly understood disease in children. It is generally accepted that PNH in children is characterized by severe bone marrow failure, less intensive hemolysis, and less often complicated by thrombosis and organ dysfunction. Aim: to compare the clinical and laboratory characteristics and to determine the long-term prognosis of PNH with disease onset in children and adults. Retrospective and prospective study included patients with active hemolytic PNH, defined by flow cytometry results (clone more than 10% in granulocytes), clinical and laboratory criteria (lactate dehydrogenase (LDH) level above 1.5 of the upper limit of normal (ULN)). The classical PNH and aplastic anemia/PNH (AA/PNH) were studied. A detailed analysis of clinical manifestations, primary diagnoses, complications and overall survival was performed depending on the age of PNH onset (before and after age 18 years). As of August 2018, 355 patients were included in the study (56% female, 44% male) with classic form (49%) and AA/PNH (51%). The median age at the PNH onset and the diagnosis was 27 (5–80) and 30 years (7–80), respectively. The median PNH clone size in granulocytes and red blood cells was 92% and 33%, respectively, and the LDH level of 5.5 ULN. Hemolytic PNH onset during childhood was in 51 patients (14%) with the same frequency of classical form (n = 27; 16%) and AA/PNH (n = 24, 13%) ( p = 0.549). The diagnosis of classical form and AA/PNH was confirmed in childhood in 9 (5%) and 21 (12%) patients respectively. In 81% of classical PNH presenting in children, a misdiagnosis was initially established, and the median time before precise diagnosis was 52 months (4–426). The PNH clone size (median 93% vs 91%, p = 0.321) and hemolysis intensity according to LDH level (median 4.95 vs. 5.76 ULN, p = 0.690) did not differ in children and adults. The frequency of hemolysis symptoms in the onset of the disease correlated with the clone size and was higher in classical PNH compared with AA/PNH, but did not depend on onset age: weakness (98% in children vs. 96% in adults), hemoglobinuria (51% vs 55%), pain (39% vs 45%), jaundice (46% vs 52%), dysphagia (21% vs 28%). The age of PNH onset did not influence the frequency of early (before the diagnosis of PNH) thrombosis (8% vs 13%, p = 0.482) and episodes of acute kidney injury (AKI, 10% vs 9%, p = 0.788). With prolonged follow-up, there is a tendency towards a higher cumulative incidence of thromboses in adults: 5 years 21% vs 12%, 10 years 33% vs 19%, however in the more distant period these differences become insignificant ( p = 0.151). The cumulative incidence of AKI was similar in children and adults: 5 years 16% vs 20%, 10 years 23% vs 22%, respectively ( p = 0.500). The frequency of transfusion dependence, the development of chronic kidney disease and pulmonary hypertension and overall survival were also independent of the PNH onset age. The results of the study in the large cohort of patients indicate the similar clinical profile and a long-term prognosis of active hemolytic PNH in children and adults. Diagnostic errors and late recognition of classical PNH lead to the relative prevalence of AA/PNH in children.

Treatment results of hematopoietic stem cells transplantation (HSCT) with myeloablative (MAC) and reduced intensity (RIC) conditioning regimen in children and adolescents with myelodysplastic syndrome (MDS). Fifty seven patients aged 1to18 years who received allo-HSCT from 1996 to 2016 (30 patients with MAC and 29 patients with RIC) are included in the study. Analysis of overall and event-free survival in both groups showed comparable efficacy. The use of RIC as alternative conditioning regimen in children and adolescents with MDS.

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.

Background & Aims. The aim of the study was to evaluate the efficacy and safety of azacytidine and decitabine prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia. Materials & Methods. The research included 62 patients who received hypomethylating agents (HMA) prior to allo-HSCT. The median age was 28 years (range from 1 to 68 years), the study population consisted of 27 (43.5 %) women and 35 (56.5 %) men. Results. The overall response (complete + partial remission) was observed in 42 % (n = 26) of cases. At the time of allo-HSCT no disease progression was observed in 41 (66 %) patients. The multivariant analysis showed the overall survival (OS) statistically significantly increased with the graft retention (hazard ratio [HR] 0.002; 95% confidence interval [95% CI] 0.001-0.74; p = 0.03), and also with the administration of HMA after allo-HSCT (HR 0.24; 95% CI 0.08-0.67; p = 0.007). The response (stabilisation, partial or complete remission) due to HMA administration prior to allo-HSCT (HR 6.4; 95% CI 0.75-54.0; p = 0.08) was associated with improved OS. The event-free survival (EFS) was significantly higher with the response to azacytidine and decitabine at the time of allo-HSCT (HR 38.9; 95% CI 1.3-1198.0; p = 0.03) and with the graft retention (HR 0.02; 95% CI 0.005-0.1; p = 0.001). In patients with MDS compared with AML (HR 2.3; 95% CI 0.9-22.0; p = 0.08), there was a tendency to EFS improvement. Progression-free survival rates were higher in patients with a number of blast cells in the bone marrow less than 31 % at the time of diagnosis (HR 1.1; 95% CI 1.1-9.9; p = 0.01). Conclusion. The use of azacytidine and decitabine prior to allo-HSCT allows to safely control the tumor mass in patients with MDS and to maintain the achieved remission with AML. In patients with a response to HMA, the best OS and EFS values are seen after allo-HSCT.