This study presents the results of treatment of 339 patients with acute promyelocytic leukemia (APL) from 57 regions of the Russian Federation (RF) and the Republic of Belarus (RB) according to the 2003/2008 APL treatment protocols, from 2008 to 1 January 2024. Based on the data from the AML-MRD-2018 protocol, the proportion of APL among childhood acute myeloid leukemia (AML) cases in the RF was investigated. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. It was established that the APL cases comprised 26% of AML cases, and APL incidence rate varied across the regions of the RF. Our findings suggest that the incidence of APL in Russian children is higher than in children from Europe and the USA, but further epidemiological research is needed to confirm this. The 5-year overall (OS) and event-free (EFS) survival rates in the patients treated according to the 2003/2008 APL protocols were 82% (95% confidence interval (CI) 78–86) and 73% (95% CI 67–78), respectively. In the low-risk group (LRG) the five-year OS and EFS rates were statistically significantly higher than in the high-risk group (HRG), with 5-year OS reaching 93% (95% CI 89–97) in the LRG and 63% (95% CI 55–72) (p 0.001) in the HRG, and EFS – 85% (95% CI 79–91) and 52% (95% CI 44–63) (p 0.001), respectively. The risk of relapse was higher in the HRG: 15% (95% CI 9.1–25) in the HRG vs 8.7% (95% CI 4.9–15%) in the LRG (p 0.045). The difference in the survival rates in the LRG and HRG was attributable to a higher mortality rate during remission induction in the HRG as compared to the LRG: 30.1% and 2.9%, respectively. Notably, 83.7% of deaths were caused by brain haemorrhage. Decreasing early death rate is key to improving APL treatment results in children in the RF and RB.

In children under 3 years of age, lymphoma is extremely rare and may be a manifestation of inborn errors of immunity (IEIs). The aim of this study was to determine TREC/KREC copy numbers and search for Slavic founder mutations (RAG1 p.Lys86ValfsTer33, IL7R p.Ser44Arg, NBN1 p.Lys219AsnfsTer16, ATM p.Glu1978Ter, UNC13D p.Arg782SerfsTer12) in patients with lymphoma up to 3 years of age from the Belarusian Cancer Registry (No.: 0170100025) over a 26-year period. From 1998 to 2024, 39 patients younger than 3 years (29 males and 10 females) were diagnosed with lymphoma. The median age was 2.1 years (from 50 days to 2.8 years). 4 patients had Hodgkin's lymphoma (HL), 5—diffuse large B cell lymphoma (DLBCL), 13—lymphoblastic lymphoma (LL), 10—Burkitt lymphoma (BL), 2—peripheral T cell lymphoma (PTCL), 4—anaplastic large cell lymphoma (ALCL), 1—non-Hodgkin's lymphoma (NHL) of unspecified type. DNA was isolated from archival samples from 36 patients: bone marrow smears (n = 12), frozen bone marrow cells (n = 11), and peripheral blood cells (n = 13). Lymphoma in children aged 0-3 years accounted 3% (39/1237) of all pediatric lymphoma cases up to 18 years of age, including 7% (35/481) of NHL and 0.5% (4/756) of HL patients. 15/39 (38%) patients died and 3 were lost to follow-up. TREC/KREC copy numbers was reduced in 12/36 (33%) patients, 7 of whom were dead. Low TRECs/KRECs were present in all patients with DLBCL, 2 with ALCL, 2 with LL, and single cases with HL, BL, and PTCL. Homozygosity for the underlying Slavic variant of RAG1 [p.Lys86ValfsTer33] was found in a patient with DLBCL at the age of 14 months. One 12-month-old patient with PTCL was homozygous for the founder Slavic UNC13D variant [p.Arg782SerfsTer12]. Low TREC/KREC was detected in one-third of children aged 0-3 years with lymphoma and may be used as a step 1 method to suspect the IEIs.

BACKGROUND:Quantitative measurement of minimal residual disease (MRD) is the "gold standard" for estimating the response to therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP-ALL, in terms of genetic subgroups with relation to clinically defined risk groups. METHODS:A total of 485 children with non-high-risk BCP-ALL with available cytogenetic data and MRD studied at the end-of-induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard-risk (SR) of intermediate-risk (ImR) regimens of "ALL-MB 2008" reduced-intensity protocol. RESULTS AND DISCUSSION:Among all study group patients, 203 were found to have low-risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC-MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC-MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low-(0.03%) and intermediate (0.01%) cytogenetic risk groups. CONCLUSION:Our data show that combining clinical risk factors with MFC-MRD measurement is the most useful tool for risk group stratification of children with BCP-ALL in the reduced-intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.

In children with acute myeloid leukemia (AML) who lack a human leukocyte antigen (HLA) identical sibling, the donor can be replaced with an HLA-matched unrelated donor (MUD) or a haploidentical donor (haplo). We compared outcomes of patients <18 years with AML in first and second complete remission (CR1 & CR2) undergoing a hematopoietic stem cell transplantation (HCT) either with a MUD with anti-thymocyte globulin (ATG) (N=420) or a haplo HCT with post-transplant cyclophosphamide (PT-CY) (N=96) after a myeloablative conditioning regimen (MAC) between 2011 and 2021, reported to the European Society for Blood and Marrow Transplantation. A matched pair analysis was performed to adjust for differences among groups. The final analysis was performed on 253 MUD and 95 haplo-HCT. In the matched cohort, median age at HCT was 11.2 and 10 years and median year of HCT was 2017 and 2018, in MUD and haplo-HCT recipients, respectively. The risk of grade III-IV acute graft-versus-host disease (aGVHD) was significantly higher in the haplo group (hazard ratio [HR]=2.33, 95% confidence interval [CI]: 1.18-4.58; P=0.01). No significant differences were found in 2 years overall survival (OS; 78.4% vs. 71.5%; HR=1.39, 95% CI: 0.84-2.31; P=0.19), leukemia-free survival (LFS; 72.7% vs. 69.5%; HR=1.22, 95% CI: 0.76-1.95; P=0.41), CI of relapse (RI; 19.3% vs. 19.5%; HR=1.14, 95% CI: 0.62-2.08; P=0.68) non-relapse-mortality (NRM; 8% vs. 11%; HR=1.39, 95% CI: 0.66-2.93; P=0.39) and graft-versus-host free relapse-free survival (GRFS; 60.7% vs. 54.5%, HR=1.38, 95% CI: 0.95-2.02; P=0.09) after MUD and haplo-HCT respectively. Our study suggests that haplo-HCT with PT-CY is a suitable option to transplant children with AML lacking a matched related donor.

This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 of induction therapy in children with B-lineage ALL. Methods. Conventional induction therapy consisted of dexamethasone, vincristine, and daunorubicin. MRD data was available in 502 patients who were randomized at the start of induction therapy, standard-risk (SR) patients into three (conventional induction without PEG, induction with additional PEG and with PEG but without daunorubicin) and intermediate-risk (ImR) patients into two groups (with additional PEG and without PEG). Results. The single administration of PEG resulted in a significantly higher proportion of rapid responders, in SR patients even when no anthracyclines were used for induction. In the SR group, the event-free survival of the MFC-MRD fast responders was similar in the PEG− and PEG+ arms (92.0 ± 3.1% vs. 96.2 ± 1.5%, respectively), and the same unfavorable trend was observed for MFC-MRD slow responders (57.5 ± 12.3% vs. 66.7 ± 15.7%, respectively). Results were similar in ImR patients: (94.3 ± 3.2% vs. 95.1 ± 2.4%, for fast responders and 63.3 ± 7.6% vs. 78.1 ± 7.9%, for slow responders in PEG− and PEG+ arms, respectively). However, there is a large difference between the proportion of MFC-MRD slow responders in the PEG− and PEG+ groups (18.3% vs. 5.2% for the SR group and 44.2% vs. 25.0% for the ImR group). Conclusions. Therefore, early use of PEG-ASP not only leads to an accelerated reduction of blasts, but also to an excellent outcome in a significantly larger proportion of patients in both risk groups.

Hemophilia A is the most common severe bleeding disorder caused by various genetic changes in the F8 gene, leading to coagulation factor VIII deficiency. Hemophilia A is characterized by high heterogeneity of genetic defects. The severity of hemophilia A varies depending on the type of genetic defects in the F8 gene. More than 3000 unique variants of the F8 gene are associated with the hemophilia A. Approximately 30% of genetic defects occur de novo. The aim of this study is to determine the spectrum of genetic defects in the F8 gene in children with hemophilia A in Belarus. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). The study included 98 patients with hemophilia A, who had been treated or followed up at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Patients were categorized into 3 groups based on the severity of their disease: severe (n = 82), moderate (n = 3), and mild (n = 13). Twenty (20.4%) patients had a history of inhibitors to factor VIII. For our study, we used venous blood samples. Genomic DNA was isolated from leukocyte suspension (obtained from the whole blood samples) using phenol-chloroform extraction. All severe hemophilia A patients were prescreened for intron 22 and 1 inversions in the F8 gene using inverse and multiplex polymerase chain reaction assays, respectively. Sequencing of F8 coding regions was carried out by next generation sequencing. All clinically relevant variants were confirmed by Sanger sequencing. Genetic testing revealed that 99% of the patients with hemophilia A (n = 97) had pathogenic variants in the F8 gene. Intron 22 and intron 1 inversion mutations within the F8 gene were detected in 45.1% (n = 37) and 1.2% (n = 1) patients with severe hemophilia A, respectively. Two patients had an abnormal pattern of intron 1 inversion, not previously described in the literature. A total of 48 different variants in the F8 gene were detected in 57 patients using next generation sequencing. Eleven of the 48 genetic variants identified have not been previously reported.

Key Clinical MessagePartial leukocyte adhesion deficiency type 1 (LAD‐1) deficiency is extremely rare condition with milder infectious manifestation and immune system imbalance leads to increased risks of autoinflammatory complications, such as pyoderma gangrenosum, that can be triggered by trauma or pregnancy. In patients with spice‐site ITGB2 variants, partial expression can occur due to different β2 integrin isophorms expression.AbstractLAD‐1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 β2 integrin subunit. According to the CD18 expression, LAD‐1 is categorized as severe (<2%), moderate (2%–30%), or mild (>30%). Here, we describe a 22‐year‐old female, who presented with inflammatory skin disease and oral cavity, as well as respiratory tract infections during the first year of life. LAD‐1 was diagnosed at the age of 2 years by low expression of CD18 (1%). Whole‐exome sequencing identified homozygous c. 59‐10C>A variant in the ITGB2 gene. Despite severe phenotype, the patient survived to adulthood without hematopoietic stem cell transplantation and became pregnant at the age of 20 years, with pregnancy complicated by a pyoderma gangrenosum‐like lesion. During her life, CD18 expression increased from 1% to 9%; at 22 years of age, 5% of neutrophils and 9% of lymphocytes were CD18+. All CD18+‐lymphocytes were predominantly memory/effector cytotoxic T cells. However, revertant mosaicism was not being established suggesting that CD18 expression variability may be mediated by other mechanisms such as different β2 integrin isophorms expression.

Sequential monitoring of minimal residual disease (MRD) by molecular techniques or multicolor flow cytometry (MFC) has emerged over the past two decades as the primary tool to optimize treatment in pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). The aim of our study was to compare the prognostic power of repeated MFC–MRD measurement with single‐point MRD assessment in children with BCP‐ALL treated with the reduced‐intensity protocol ALL‐MB 2008. Data from consecutive MFC–MRD at day 15 and day 36 (end of induction, EOI) were available for 507 children with Philadelphia‐negative BCP‐ALL. They were stratified into standard risk (SR, n = 265), intermediate risk (ImR, n = 211), and high risk (HR, n = 31) according to the initial clinical characteristics defined in the ALL‐MB 2008 protocol. Quantitative (relative to quantitative thresholds) and kinetic (logarithmic reduction) assessments of MFC–MRD at both time points effectively separated patients into three groups with different risk of recurrence. On the other hand, starting with low (for the SR group) and moderate (for the ImR group) induction therapy, a single MFC–MRD measurement at EOI proved sufficient to unequivocally identify patients in whom this therapy is highly effective and distinguish them from those who cannot be successfully treated with such therapy. Therefore, initiating treatment with low or moderate treatment from the start, together with careful consideration of initial clinical risk factors and just one EOI–MFC–MRD measurement is simple, inexpensive, and entirely sufficient for treatment optimization. Furthermore, for a large proportion of patients, this approach allows better adjustment, in particular also reduction of therapy intensity than sequential MRD measurements.

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A‐g) B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) treated consistently according to the MLL‐Baby protocol, a moderate‐intensity protocol. Of the 139 patients enrolled in the MLL‐Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A‐r), while the remaining 39 infants (28.1%) had KMT2A‐g. KMT2A‐g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)‐positive, and more likely to be CD10‐positive. The 6‐year event‐free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate‐intensity therapy, as used in the MLL‐Baby protocol in infants with KMT2A‐g BCP‐ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)‐MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.

The achievement of remission at the end of induction (EOI) chemotherapy in patients with acute lymphoblastic leukemia (ALL) is the key parameter of treatment effectiveness evaluation. The aim of the study – defining complete remission by multicolor flow cytometry (MFC) and bone marrow (BM) cytomorphology (CM) at the EOI chemotherapy in children with B-lineage ALL. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included patients of “ALL-MB 2008” and “ALL-MB 2015” trials for whom minimal residual disease (MRD) was evaluated by MFC at the EOI simultaneously with CM BM investigation. Less than 5% blasts in BM and MRD < 1% were established as the remission achievement criteria for CM and MFC respectively. The study group included 1498 children aged from 1 to 18 years (median age was 4 years and 11 months) with B-cell precursor ALL. The overall concordance of MFC and CM was found to be 96.1% (1440 of 1498 patients). In 36 (2.4%) children with MRD ≥ 1%, M1 BM status was observed. In contrast, in 22 (1.5%) patients with M2/M3 BM status by CM, MRD value was below 1%. Treatment outcome was analyzed in 522 patients of “ALL-MB 2008” trial. Children with M2/M3 BM, as well as with MRD ≥ 1% demonstrated dramatically inferior outcome, in comparison to those who achieved remission. The presence of at least one of the mentioned criteria (M2/M3 status by CM or MRD ≥ 1% by MFC) defined a group of 23 (4.4%) patients with very low event-free survival (34.9%, standard error 11.0%) and very high cumulative incidence of relapse (56.4%, standard error 12.0%). For the evaluation of remission achievement, MFC and CM should be applied simultaneously at the EOI. High leukemic burden found by any of these methods is the clear definition of induction failure. MRD detection at the EOI should be implemented in any modern treatment protocol as an obligatory stage of treatment response monitoring and final risk group stratification. Considering the crucial importance of the MRD detection results, this study must be performed only in the reference laboratories of the study groups.

Serious side effects occur during therapy for childhood acute lymphoblastic leukemia (ALL), and survivors can experience long-term consequences. This study aimed at identifying patients who can be successfully treated with low treatment intensity combining clinical parameters and minimal residual disease (MRD) measurements. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. ALL-MB studies used reduced-intensity therapy from the beginning, for standard risk (SR) patients no cyclophosphamide, a very low daunorubicin dose, no high dose of methotrexate, no cranial irradiation. In the ALL-MB 2008 study, 1702 children (49.1 % of all patients) were classified as SR due to favorable initial characteristics. These included 295 patients treated in institutions who took part in a pilot study on MRD measurement using flow cytometry on day 15 and/or at the end of induction (EOI). The most suitable time point for MRD measurement was EOI with threshold 0.1% in 90.5 % of the patients with excellent results: event-free survival of 95 % and overall survival of 97 %, that identified the large proportion of patients (more than 40 % of all ALL patients). The outcome of children with slower MRD response was significantly worse. Initial SR characteristics plus one single MRD measurement at EOI identify more than 40 % of all children with ALL who can be successfully treated with low-intensity regimens as used in the MB protocols.

Aim The aim of the study was to evaluate the incidence and prognostic impact of central nervous system (CNS) involvement in infants with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), as well as its relation with minimal residual disease (MRD) data. Methods A total of 139 consecutive infants with BCP-ALL from the MLL-Baby trial were studied. Cerebrospinal fluid (CSF) samples were investigated by microscopy of cytospin slides. MRD was evaluated according to the protocol schedule by flow cytometry and PCR for fusion gene transcripts (FGT). Results Involvement of the CNS at any level was found in 50 infants (36.0%). The incidence of CNS involvement was higher in patients with KMT2A gene rearrangements (44.0% for KMT2A-r vs. 15.4% for KMT2A-g, p = .003). The outcome of CNS-positive infants was significantly worse than that of CNS-negative infants, although this prognostic impact was limited to the KMT2A-r group (event-free survival 0.21 for CNS-positive vs. 0.48 for CNS-negative infants, p = .044). CNS-positive infants could not be treated successfully by conventional chemotherapy alone, irrespective of the rapidity of MRD response. In contrast, the combination of initial CNS negativity and FGT-MRD negativity identified a group comprising up to one-third of infants with KMT2A-r ALL who can be treated with chemotherapy and achieve very good outcomes (disease-free survival above 95%), and remaining patients should be allocated to receive other types of treatment. Conclusion We can conclude that this combination of initial CNS involvement and MRD data can significantly improve risk-group allocation in future clinical trials enrolling infants with ALL.

Prognosis of patients with acute myeloid leukemia receiving intensive chemotherapy is defined as kariotyping anomalies, and mutations of genes responsible for surviving and self-maintenance leukemic cells. In the giving work incidence of mutation involving genes FLT3, c-KIT, NPM1 having prognostic value in adults is analysed. Kynase domain FLT3 mutation in 18 from 83 patients (21.6%) was detected. 2 from 18 patients (11%) achieved complete remission, 5 from 18 patients (27.7%) with FLT3 mutations were refractory to therapy, two patients died from treatment complications, 9 from 18 (50%) relapsed. Only 2 patients (11%) are alive in continuous complete remission. с-KIT mutations detected in 14.2% (2/14 patients), and NPM1 mutations represented allelic polymorphism. Thus, kynase domain FLT3 mutation are prognostic unfavorable.

Гемофилия A – наиболее распространенное тяжелое нарушение свертываемости крови, вызванное отсутствием или снижением активности фактора свертывания крови VIII вследствие генетических аномалий в гене F8. Примерно у половины пациентов с тяжелой формой гемофилии А выявляется инверсия 22 интрона гена F8. Взаимосвязь между инверсией 22 интрона и тяжестью заболевания обусловлена ее влиянием на формирование полноразмерного транскрипта мРНК, что приводит к формированию усеченного и нефункционирующего белка FVIII и, как следствие, тяжелой гемофилии А.Обнаружение мутаций играет важную роль в прогнозировании осложнений проводимой заместительной терапии, поскольку генетические аномалии, приводящие к дефектному белку FVIII, связаны с 20–80%-ным риском образования ингибиторов у пациентов с тяжелой формой гемофилии А.Целью настоящего исследования было провести молекулярно-генетическую диагностику инверсии 22 интрона гена F8 и оценить ее частоту встречаемости среди пациентов с тяжелой формой гемофилии А в Республике Беларусь. В исследование был включен 71 пациент с тяжелой формой гемофилии А. У 21,1% (n=15) пациентов в анамнезе имелись данные об образовании ингибиторов к фактору VIII. Анализ инверсии 22 интрона был выполнен с использованием метода инвертированной полимеразной цепной реакции. В результате исследования инверсия 22 интрона гена F8 была детектирована у 46,5% пациентов с тяжелой формой гемофилии А. У 39,5% пациентов наблюдалась инверсия 22 интрона 1-го типа, у 7% – инверсия 22 интрона 2-го типа. Среди пациентов с инверсией 22 интрона ингибиторы вырабатывались в 36,4% случаев. Hemophilia A is the most common severe bleeding disorder caused by a lack or decreased activity of coagulation factor VIII due to genetic abnormalities in the F8 gene. In about half of patients with severe hemophilia A, the intron 22 inversion of the F8 gene is detected. The relationship between intron 22 inversion and the severity of the disease is due to its effect on the formation of a full-length mRNA transcript, which leads to the formation of a truncated and non-functioning protein FVIII and subsequently to severe hemophilia A. The detection of mutations plays an important role in predicting the complications of substitution therapy, as far as genetic abnormalities, leading to a defective protein FVIII are associated with a 20–80% risk of inhibitor development in patients with severe hemophilia A.The aim of this study was to carry out molecular genetic diagnostic of intron 22 inversion of the F8 gene and to assess the frequency of occurrence among patients with severe hemophilia in Belarus. The study included 71 patients with severe hemophilia A. 21.1% (n=15) of patients had a history of the formation of inhibitors to factor VIII. Analysis of intron 22 inversion was performed using inverse polymerase chain reaction. In result of the study, intron 22 inversion of the F8 gene was detected in 46.5% of patients with severe hemophilia A. In 39.5% of patients, the intron 22 inversion of type 1 was observed, in 7% of patients, the intron 22 inversion of type 2 was observed. Among patients with 22 intron inversion, inhibitors were produced in 36.4% of patients.

Comparative pharmacoeconomic analysis of treatment according to ALL-MB-2002 protocol between two groups of children with acute lymphoblastic leukemia (ALL) (n=53) depending on use of intravenous immunoglobulin (IVIG) aiming to infectious complications preventing was conducted. It is shown, that actual protocol cost in group of children treating with IVIG in 1,5 times low (р<0,001). Price reduction of medicamentous treatment in this group of patients occur due to reduction of complications treatment cost, p<0,001. Decreasing time of treatment interruptions in group of patients with IVIG result in severe reduction of hospitalization cost (p<0,001). Application of this drug is more economic because of almost in 2 times reduction cost/efficiency ratio and 1,4 times increasing of additional years of life in ALL patients.

Protocol AML-MM-2000 treatment results of unfavorable prognostic group in children with primary acute myeloid leukemia (AML) in Russia and Belarus are presented. 105 children at the age from 2 weeks till 18 years (a median age — 10.8 years) are included in the study. In 91 patients (86.7%) hematological remission have reached, from them 34 patients (37.4%) are in the first continuous complete remission (CCR). 6-years overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) rate for all group of patients was 0.35 ±} 0.05; 0.32 ±} 0.04 and 0.43 ±} 0.05, respectively. Survival analysis of children with different cytogenetic anomalies has allowed to define two prognostic groups of patients: the intermediate prognosis, including patients with normal kariotype and t(9;11) which EFS and RFS rate was 40—50%, and unfavorable prognosis with EFS and RFS rate less than 40%. The efficiency analysis of three postremission therapy type (allogeneic and autological hematopoietic stem cells transplantation (HSCT) and chemotherapy (HT)) in intermediate and unfavorable prognostis groups was carried out. High efficiency of related HLA-identical HSCT in patients both intermediate and unfavorable prognostis groups have been shown. Autological HSCT is possible in intermediate prognosis patients with absence of HLA-identical siblings and in unfavorable prognosis patients with absence of HLA-identical unrelated donor.

The excellent results of posttransplant cyclophosphamide in decreasing graft-versus-host disease (GVHD) after haploidentical (HI) allogeneic transplant have challenged current donor selection algorithms.We compared outcomes after matched sibling (MSD) versus alternative donor transplant using identical graft-versus-host disease (GVHD) prophylaxis including posttransplant cyclophosphamide (PTCy. Endpoints included engraftment, time outside of the hospital in the first 100 days after transplant, overall survival (OS), non-relapse mortality (NRM) and percentage of patients disease-free and off immunosuppression (DFOI) at one year and at the last follow-up.There were significant differences at baseline between matched donor versus HI donor transplants with higher disease-risk index (DRI), more female-to-male donor recipient pairs and a higher percentage of Black patients in the HI group. Engraftment and time out of the hospital favored MSD and matched unrelated donor transplants. Multivariate analysis showed that high DRI and Black race were associated with decreased survival and Black race was associated with a higher NRM.With the use of PTCy, our results support current donor selection algorithms. The finding of decreased survival and increased NRM in Black patients requires confirmation in a larger number of patients as well as the development of mitigation strategies.

The paper presents the results of a multicenter randomized study of two-dose COLI-ASP regimens in therapy of consolidation of standard risk-group (SRG) children and adolescents with acute lymphoblastic leukemia (ALL) treated by the ALL-MB-2002 protocol. The principal aim of the study was to elucidate whether the dose of COLI-ASP might be reduced without losing the efficiency of therapy. The analysis covered primary ALL patients notified at 36 clinics of Russia and Belarus, enrolled for the study in the period of May 1, 2002, to October 10, 2006. Out of 819 patients to be examined, 414 received COLI-ASP in a dose of 10,000 U/m2 (a control group), and 405 children took it in a dose of 5,000 U/m2 (a study group). No statistically significant differences were found between the patients in gender, age, baseline leukocytosis, and spleen size. The study showed no statistically and clinically significant differences in event-free, overall, and relapse-free survival (EFS, OS, and RFS, respectively) and relapse rates with the use of two-dose COLI-ASP regimens. However, in the control group, the death rate in remission was twice greater than that in the study group (p = 0.02). Detailed analysis of the outcomes of therapy in some subgroups revealed no differences between the control and study groups. The Cox multiple regression analysis has indicated that the factors influencing EFS and RFS are the baseline sizes of the spleen, baseline leukocytosis, age, and a response to treatment in the period of induction, rather than the dose of E. coli asparaginase. The authors have also found that among the SRG patients, there is a subgroup of patients without risk factors, in whom the reduction in the COLI-ASP dose may substantially increase survival rates, by lowering toxicity and mortality in remission.