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Aim. Remission induction can be associate, with the life threatening complications and transfer to ICU of de novo acute myeloid leukemia (AML) patients (pts). We evaluate influence of transfer to ICU and life threatening complication on early mortality and long - tram survival of de novo AML pts. Materials and methods. Retrospective study. All de novo AML pts younger than 60 years old admitted in the National Research Center for Hematology from 2013 to 2016 years were enrolled in the study. Patients were divided into 2 groups: pts who were required ICU admission during remission induction (ICU-pts) and pts who did not require ICU admission and received chemotherapy only in hematology ward (non-ICU pts). The reasons for ICU admissions and results of life support were analyzed. Overall survival (OS) were assessed by the Kaplan-Meier method, long rank value p

Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

The case report of botulinum toxin treatment of gastroparesis in a patient following allogenic bone marrow transplantation is described. The causes of gastroparesis and methods of prevention and treatment are discussed. It was noted that pyloric injection of botulinum toxin can improve symptoms and gastric emptying.

Aim. To evaluate the detection rate of markers for hepatitis B virus (HBV) in the blood samples taken from patients with blood system diseases, by applying the current approaches to examining donated blood and its components for markers of viral infections. Materials and methods. The investigation included blood samples from patients with blood system diseases (n=364) and donors (n=5,011). The results of laboratory screening of donated blood samples (n=13,081) were retrospectively analyzed. Commercial kits of reagents were used for immunochemical assay and polymerase chain reaction. Results. Patients with blood system diseases were recorded to have markers of active HBV infection in 12.6% of cases, anti-HBc in 31.3%, and anti-HBs in 37.6%. A retrospective analysis of the results of screening donated blood samples showed the presence of markers for active HBV infection in 0.28% of cases. A prospective examination of blood donors revealed markers of HBV infection in 4.83% of cases, including those of active forms in 0.54% and anti-HBc in 4.79%. The markers of active HBV infection in donors were only anti-HBc IgM in 0.42% of cases. The blood samples from donors with an anti-HBs titer of >200 mIU/ml contained anti-HBc IgM in 10.5%. Conclusion. In the last 5-7 years, the detection rate of markers of HBV infection in the blood samples of patients with blood system diseases have remained at a high level. Screening for decreed markers fails to identify people with inapparent infections among the donors. Even high anti-HBs concentrations in the donated blood may be a risk for HBV transmission by transfusion to a recipient.

Aim. To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). Subjects and methods. In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year. On day 100 after auto-HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by 6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a criterion for evaluating the efficiency of maintenance therapy. Results. After auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to 70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD statistically significantly increased the risk of relapse (odds ratio 1.7; 95% CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan-Meier) after auto-HSCT did not statistically significantly differ in MRD-negative patients receiving (n=15) and not receiving (n=10) maintenance therapy with bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD-positive patients achieved a negative status. In the MRD-positive patients who had received maintenance therapy, the average time to recurrence was 5 months longer than that in the naïve patients: 17.3 versus 12.3 months. Conclusion. The MRD status determined in MM patients who have achieved CR after auto-HSCT is an important factor for deciding on the use of maintenance therapy.

Aim. To identify a parameter predicting a collection of at least 2·106 CD34+ hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure. Subjects and methods. The investigation included 189 patients with hematological malignancies and 3 HSC donors, who underwent mobilization of stem cells with their subsequent collection by LA. Absolute numbers of peripheral blood leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+ cells/kg body weight (BW) in the LA product stored on the same day were determined in each patient (donor). Results. There was no correlation between the number of leukocytes and that of stored CD34+ cells/kg BW. There was a close correlation between the count of peripheral blood CD34+ cells prior to LA and that of collected CD34+ cells calculated with reference to kg BW. Conclusion. The optimal absolute blood CD34+ cell count was estimated to 20 per µl, at which a LA procedure makes it possible to collect 2·106 or more CD34+ cells/kg BW.

Double-hit lymphoma (DHL) is a rare aggressive B-cell lymphoma with concomitant c-MYC, BCL2 or BCL6 gene rearrangements, which is characterized by the high frequency of extranodal lesions and by resistance to chemotherapy. The median survival does not exceed 18 months in patients with this disease. The majority of DHL is represented by с-MYC/BCL2 cases. The combination of c-MYC/BCL6 occurs rarely (5—8%). The paper describes a case of DHL with concomitant c-MYC and BCL6 gene rearrangements, which mimics diffuse large B-cell lymphoma, leg-type.

Background. Mycosis fungoides (MF) is classified as an orphan disease. Due to the rarity of pathology, and until recently the absence of an expert group and a specialized reference center for cutaneous lymphomas in Russia, possible treatment options for MF are presented by listing them without recommendations on the preferred indications for one or another option. This creates difficulties in choosing treatment methods and assessing their effectiveness.Aim. To characterize current treatment methods and their results in MF patients who were observed or received consultative and diagnostic care at the National Medical Research Center for Hematology.Materials and methods. The study included 210 patients: 115 with early disease stages and 95 with advanced stages.Results and conclusion. The most common treatment options were for early stages – local therapy, interferon therapy and systemic chemotherapy (CT), for advanced stages – combination therapy with interferon (+ PUVA therapy, methotrexate), interferon monotherapy and systemic CT. The frequency of systemic chemotherapy use in all lines of MF treatment was 21 %. When integrating statistical analysis using the probability of achieving an antitumor response, switching to 2nd line therapy, and accumulated incidence, the negative results of using chemotherapy in the MF treatment were clearly demonstrated.For the first time in Russia, a real practical situation of the applied MF treatment options is presented on our own large sample of patients. As the first line of therapy, the most common options were immunotherapy and phototherapy, however, in 12.4 % of cases, the use of systemic CT was registered, which is unjustified and leads to a decrease in the time to the next line of treatment and an increase in the cumulative incidence of adverse events. As a result of the use of non-chemotherapeutic approaches (interferon, etc.), the 3-year relapse-free survival rate is about 40 %, after chemotherapy – 9.4 %. Secondand third-line therapy provided more varied options, including combination treatment with interferon and methotrexate, as well as gemcitabine monotherapy, targeted therapy with brentuximab vedotin, and epigenetic therapy in the 3rd line. Studies with targeted agents in this patient population have demonstrated improved clinical outcomes, highlighting the need for their early use to achieve the best results.

Aim. To analyze well-known risk factors (RFs), such as age, immunophenotype, baseline leukocytosis, enhanced lactate dehydrogenase (LDH) activity, time to achieve complete remission, a risk group, and cytogenetic abnormalities) in patients with acute lymphoblastic leukemia (ALL) in the use of the ALL-2009 protocol. Subjects and methods. The protocol covered 298 patients (137 women (including 13 pregnant women) and 161 men) aged 15 to 55 years (median age 28 years) with Ph-negative ALL. The phenotype was unknown in 6 patients. Three (1%) were ascertained to have a biphenotypic variant. 182 (62.4%) patients were found to have B-cell ALL (early pre-B ALL (n=51); common ALL (n=92), and pre-B ALL (n=39); 107 (36.6%) patients had T-cell ALL (early T-ALL (n=56); thymic T-ALL (n=41), and mature T-ALL (n=10). According to the baseline clinical and laboratory parameters (leukocytosis of 30·109/l and more for B-ALL; and that of 100·109/l and more for T-ALL; phenotype В-I for B-ALL, phenotype Т-I-II-IV for T-ALL; LDH activity was more than twice the normal values; the presence of translocation t(4;11)), the high-risk group included most patients with B-ALL (n=110 (72.8%)) and T-ALL (n=76 (76%)). Thirty-five patients with T-ALL underwent autologous bone marrow transplantation (BMT). Allogeneic BMT was performed in 18 (7%) of the 258 patients who had undergone an induction phase. Results. Five-year overall survival for all the patients included in the investigation was 59%; relapse-free survival was 65%, which was significantly different in the patients with B-ALL and in those with T-ALL: the overall survival rates were 53.3 and 67.5% (p=0.1); the relapse-free survival was 56 and 79% (p=0.005), respectively. Multivariate analysis including the well-known RFs demonstrated that the latter for T-ALL were of no independent prognostic value and only the patient’s age was identified for B-ALL (p=0.013). Conclusion. A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.

In the past decade, a notable advance has been made in the understanding of the pathogenesis of NK/T-cell lymphomas; however, their diagnosis remains difficult because of their rarity and clinical and morphological variabilities. The paper generalizes the ten-year experience of the Hematology Research Center, Ministry of Health of Russia, in diagnosing and treating hepatosplenic T-cell lymphoma (HSTL), considers the problems of differential diagnosis with other hematological diseases occurring with similar clinical and laboratory symptoms, and lays down current approaches to the diagnosis and treatment of this condition. A clinician’s view of the problem of diagnosis and treatment of this disease is given. HSTL is shown to be a heterogeneous group of diseases differing in a T-cell receptor chain gene rearrangement, the clinical course of the disease, and overall survival (OS). According to our data, 3-year OS was 12%; the median survival was 26 months. Two-year OS for γδ and αβ HSTL was equal to 25 and 70%, respectively. The difference in OS for the variants of HSTL failed to reach statistical significance (because the sample might be insufficient).

Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.

Aim. To study the impact of the genes of donor killer cell immunoglobulin-like receptors (KIR) and HLA—KIR ligands on overall (OS) and event-free survival (EFS) rates in patients with myeloid leukemia after transplantation with allogeneic hematopoietic stem cells (allo-HSCT) from HLA-identical related and HLA-compatible unrelated donors. Subjects and methods. The investigation enrolled 29 patients who had undergone allo-HSCT from KIR-genotyped donors at the Department of Bone Marrow Transplantation, Hematology Research Centerб in 2010-2013. OS and EFS rates after allo-HSCT were calculated using the Kaplan-Meier method. Results. The main predictor of recurrence and survival in patients after allo-HSCT was a recurrence-risk group the patient belonged to before transplantation. The standard-risk group patients whose donors had telomeric gene-content motifs of KIR-B haplotypes had higher EFS rates than those whose donors lacked these genes. The standard-risk patients homozygous for HLA-1 alleles (i.e. without HLA-C2 ligand) tended to have higher EFS rates, so did the patients without HLA-Bw4 ligand. Conclusion. The donors having telomeric gene-content motifs of KIR-B haplotypes are more preferred for allo-HSCT for patients with myeloid leukemia as the presence of donor telomeric KIR-B genes increases EFS rates in standard-risk patients.

Aim. To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy. Subjects and methods. Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group. Results. The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047). Conclusion. The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.

Aim. To evaluate the efficiency of the treatment policy for patients with acute myeloid leukemia (AML) and hyperleukocytosis (HL), which is aimed at preventing rapid hypercytolysis and massive tumor lysis (cytolysis) syndrome and/or at reducing the degree of the latter at the start of induction polychemotherapy. Subjects and methods. In 2010 to 2014, the Hematology Research Center, Ministry of Health of Russia, treated 92 patients with AML, out of them 18 patients were found to have white blood cell counts of 100 to 408∙109/l (median, 130∙109/l) at the onset of the disease. All the examinees received cytoreductive therapy with hydroxyurea and, in presence of leukostasis and/or leukocytosis (≥150∙109/l), with leukocytapheresis. In case of reduced leukocytosis, plasmapheresis was carried out to prevent (treat) cytolysis. Daunorubicin was injected on days 3—5 of the 7+3 induction cycle. Results. The signs of leukostases were detected in more than half of the 18 patients with higher white blood cell counts: 13 (72%) with lung injury, including 5 of them with signs of respiratory distress syndrome, 6 (27.8%) with neurological symptomatology, 7 (38.9%) with disseminated intravascular coagulation syndrome, including 1 with intracranial hemorrhage. Cytoreduction therapy with hydroxyurea (10 mg/kg/day) was performed 1—5 (median 2) days before initiating induction chemotherapy in 17 patients; 9 patients underwent 1—2 (median 2) leukocytapheresis sessions. Sixteen patients received 1—4 (median 2) plasmapheresis sessions prior to and within the first days of the 7+3 treatment regimen. Daunorubicin (60 mg/m2) was administered to 16 patients on days 5—7 of the 7+3 cycle and to 2 patients on days 3—5 of the cycle. There were no signs of severe cytolysis with the development of multiple organ dysfunction in any patient. 50% (9/18) achieved remission after the first 7+3 cycle and 7 more examinees did after the second cycle. Thus, the remission rate was 89%; early mortality was 5.5% (1/18), three-year overall and relapse-free survival rates were 50%. Conclusion. Adequate cytoreductive and accompanying therapies for AML with HL can virtually completely prevent massive tumor cytolysis syndrome and early mortality during the first days of induction chemotherapy.

Aim. To assess the role of allogenic bone marrow (ABM) transplantation in chronic myeloid leukemia (CML). Material and methods. 44 ABM transplantations were performed in 37 CML patients in the chronic phase and 7 patients in acceleration or blast crisis. Results. A complete molecular remission was achieved in 26 (59%) patients: 67.6% after ABM transplantation in the chronic phase and only 14.3% after myelotransplantation in non-chronic phase. Follow-up was 8-150 months (median - 59 months). Early lethality after ABM transplantation in the chronic phase was under 14%. A phase of the disease plays a key role in ABM transplantation. If it is made in a chronic phase, CML recurrence rate is low (in our series it was 14%), efficacy of donor's bone marrow lymphocyte transfusions is high. The second complete molecular remission was achieved in 3 of 4 cases of posttransplantation recurrences. Probability of maintenance of a complete remission after ABM transplantation in a chronic phase was 75%, recurrence-free survival - 64%), uneventful survival 55% for 90 months. Conclusion. The experience of many years demonstrates high efficacy of ABM transplantation in the treatment of chronic myeloid leukemia. It promotes long-term molecular remission the maintenance of which did not require therapy in 65% patients.

HLA haplotype is a block of HLA genes located on the same chromosome. Highly polymorphic HLA genes display strong linkage disequilibrium, which results in conserved multilocus HLA haplotypes. Assessment of HLA haplotypic diversity of a specific population is important, particularly for allogeneic hematopoietic stem cell transplantation. Family pedigrees remain the gold standard for studying HLA haplotype segregation. HLA haplotypes, obtained by observations of the segregation of HLA alleles within the family, really exist in the human population. The aim of this work has been to establish the frequencies of HLA haplotypes A-B-C-DRB1-DRB3/DRB4/DRB5-DQA1-DQB1-DPA1-DPB1 in families of patients with assignment to HLA-typing for allogeneic hematopoietic stem cell transplantation. The study included 109 families of patients, in which patients and their potential relative donors of allogeneic hematopoietic stem cell were subjected to HLA-typing. Patients and members of their families were typed by the NGS method in the Laboratory of Tissue Typing at the National Medical Research Center for Hematology for 11 HLA genes – A, B, C, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1 and DPB1. The genotyping was performed by the NGS method using the AllType NGS 11 Loci Amplification Kits (One Lambda, USA) on the MiSeq sequencing platform (Illumina, USA). The sequences were analyzed using the TypeStream Visual Software (TSV) (One Lambda, USA) and the IPD-IMGT/HLA database 3.44. 360 copies of HLA-haplotypes were found in the studied families. The frequencies of HLA haplotypes were determined by direct counting. The most common 7-locus haplotype was A*01:01-B*08:01-C*07:01-DRB1*03:01-(DRB3*01:01-DQA1*05:01)-DQB1*02:01/163N, the most common 9-locus haplotype was A*03:01-B*07:02-C*07:02-DRB1*15:01-DRB5*01:01-DQA1*01:02-DQB1*06:02-DPA1*01:03-DPB1*04:01P. These HLA haplotypes (in brief, A-B-C-DRB1-DQB1) are the first and second most common HLA haplotypes in most Russian registries of bone marrow donors. Despite several differences, the distribution of HLA haplotypes in families of the patients and in donor registries is similar, and the probability of finding a compatible donor for patients with common HLA-haplotypes in Russian registries is quite high. Most of 7-locus haplotypes are associated with different alleles of the HLA-DP locus in the 9-locus haplotypes, due to presence of a recombination hot spot. The study revealed strong linkage disequilibrium between the HLA alleles DRB1*03:01 and DPB1*01:01P (D’ = 0.579), DRB1*07:01, and DPB1*17:01 (D’ = 0.808), DRB1*09:01 and DPB1*04:02P (D’ = 0.502). The information obtained about real 7- and 9-locus HLA-haplotypes in families may be used in clinical practice as a reference for analyzing the results of HLA-typing and predicting the expected HLA-haplotypes. It has been shown that, despite recombination hot spot between the HLA-DP locus and the rest of the HLA complex, there is strong linkage disequilibrium between some alleles of the DRB1 and DPB1 genes.

The article provides the results of study of protein and carbohydrate nutrition for high productive cows with milk yield of 10 thousand kg during dry period. There has been carried out the research for determining the feed protein disintegration and effectiveness of its use in cow rations. The carbohydrate nutrition for Holstein-Kholmogory cows during dry period taking into account quantity and quality of neutral detergent fiber (NDF) and acid detergent fiber (ADF) was studied. The science-economic experiment was conducted in the “Polyarnaya Zvezda”, Murmansk region in 2015 and 2021. The disintegration of feed crude protein (DP) was determined by the in sacco method, by incubation of average samples of single feeds in nylon bags in the rumen during 12 hours. Content of crude protein in feed samples before and after incubation was determined by the content of total nitrogen by the Kjeldahl method. Digestibility in the intestine of feed protein not disintegrated in rumen was determined by the mobile synthetic bag method. NDF and ADF were determined by the method of Van Soest and Southgate modified by N. N. Semina. In the experiment of protein nutrition, the content of crude protein in the ration of control and experimental groups of cows was 16 %. The content of disintegrated protein in the control group was 59.0 %, in the experimental group – 67.0 %. In the experiment of carbohydrate nutrition, in the control group crude fiber was 19.4 %, neutral detergent fiber – 38.9 %, acid detergent fiber – 23.0 % of dry matter. In the ration of experimental group of cows, the content of crude fiber was 22.4 %, neutral detergent fiber – 47.2 %, acid detergent fiber – 27.6 %. Animals of the experimental group whose ration had a crude protein disintegration of 67.0% used nitrogen more efficiently, utilized a nutritious of ration better. During the research it has been established, that the content of neutral detergent fiber of up to 47.2 % and acid detergent fiber of up to 27.6 % results in increase in digestibility of ration nutritious, improves nitrogen metabolism, intensify microbiological activity in cow rumen.

Introduction. Natural killers are the "first line" of antitumor and antiviral protection in the early stages after аllogeneic hematopoietic stem cell transplantation. Quantitative characteristics reach normal values already in the first month after the infusion of blood stem cells to the recipient. Self-tolerance of natural killers is achieved due to many receptors on their surface, but killer immunoglobulin-like receptors play a key role. Their role is to recognize "self" cells and block signals aimed at destroying their own cells. Knowledge of the functional activity of natural killers urged to studying the impact of mismatches between the inhibitory receptor gene and the ligand on the development of allogeneic hematopoietic stem cell transplant failure.The aim of research was to study the probability of the graft failure development in allogeneic hematopoietic stem cell transplantation depending on the recipient's killer immunoglobulin-like receptor genotype.Material and methods. Genotyping of killer-cell immunoglobulin-like receptors in 66 recipients of blood stem cells by the polymerase chain reaction method was performed in the study. Using an online calculator, receptors were classified as "best", "better" and "neutral" depending on the genotype. The end point of the assessment was the development of graft failure in the presence of different genotypes of immunoglobulin-like receptors in the recipient.Results. According to the data obtained, the presence of the “best” and "better" killer-cell immunoglobulin-like receptor genotype in the recipient significantly increased the risks of developing various forms of graft failure.Conclusion. The presence of the KIR2DL3 genotype in a recipient of hematopoietic stem cells significantly (by 3 times) reduces the likelihood of primary graft failure. This result is of great prognostic significance, although at present no ways of influencing it have been developed. The presence of the “best” killer immunoglobulin-like receptors genotype in the recipient increases the likelihood of developing graft failure by more than 3 times compared to the best and neutral genotype (44.4% vs. 13.4%).

Background. Higher rate of gram-negative bloodstream infections (BSI) have been recently documented from transplantation centers providing fluoroquinolone (FQ) prophylaxis.Aim. To define the incidence of BSI during neutropenia according to gut mucosal colonization with resistant gramnegative bacteria and FQ administration.Materials and methods. Of 284 allogeneic hematopoietic cell transplant recipients included in the study, 154 (54.2 %) were identified as colonized with resistant gram-negative bacteria, and 130 (45.8 %) patients as non-colonized. Resistant gram-negative bacteria included Enterobacterales with extended spectrum beta-lactamase production, carbapenem-resistant Enterobacterales, Stenotrophomonas maltophilia, and carbapenem-resistant strains of Pseudomonas aeruginosa. Colonized patients did not receive FQ prophylaxis (n = 147) except 7 patients who received FQ as sequential therapy due to residual inflammatory lung lesions. Among non-colonized patients 98 received FQ prophylaxis, whereas 32 did not.Results. Probability of gram-negative BSI (71.4 %; p

Background. when transplantation of hematopoietic stem cells (HSC) is performing, it is necessary to take into account the incompatibility of the donor and recipient in terms of erythrocyte antigens in order to assess the possibility of immunological complications during HSC transfusion and/or graft engraftment (acute hemolysis, delayed hemolysis, etc.). The results of serological research methods do not always allow identifying the true group affiliation due to posttransfusion chimerism in patients and/or the presence of antigen allelic polymorphism.Aim. To establish the frequency of ABO-incompatible allo-HSC transplantations in the National Research Center for Hematology, to determine by molecular methods the group affiliation of patients with a weakened expression of antigens and/or after multiple blood transfusions before HSC transplantation, to clarify the blood type of HSC donors with a weakened expression of antigens.Materials and methods. The blood of 270 HSC donor-recipient couples was examined. The blood group of the ABO, Rhesus, MNS, Kell systems was determined in a plane agglutination test using the corresponding IgM class Tsoliclones and in gel cards. Genotyping was performed by polymerase chain reaction with primers to identify the genes of the ABO, Rhesus, Kell, and MNS systems.Results. In 2018-2020 270 HSC transplantations were performed at the National Research Center for Hematology. In 141 (52.22 %) couples, incompatibility of the donor and recipient according to the ABO system was revealed: major - 23.33 %, minor - 20 %; bidirectional - 8.89 %. problems in assessing of serological results were observed in 97 (36.3 %) patients: in 78 patients with post-transfusion chimerism and 19 patients with weakened antigen expression; in 15 (5.56 %) HSC donors: in 4 due to the lack of information about the blood group of cryopreserved cells, in 10 due to weakened antigen expression, in 1 to search for informative markers for monitoring HSC engraftment. The results of the study demonstrated that the percentage of agglutinated erythrocytes in post-transfusion chimerism cannot be a reliable criterion for establishing the true phenotype of a patient. In donors and patients with weakened expression of antigens, the presence of ABO*O1, -A1, -A2, -B1, RHD weak type 1, RHD weak type 2, RHD weak type 3, RHCE*Cw genes was confirmed. for the first time in Russia gene RHCE*01.38 was found.Conclusion. The prevalence of ABO-incompatible HSC transplants was noted. problems with serological determination of the blood group in a third of patients before HSC transplantation arose due to the presence of post-transfusion chimerism and weakened expression of antigens. Determining of the genotypes of HSC donors is necessary when the expression of antigens is weakened and cryopreserved cells are received. The percentage of agglutinated erythrocytes in post-transfusion chimerism cannot be a reliable criterion for establishing the true phenotype of a patient. Detection of mixed chimerism in the determination of group factors by serological methods is an indication for genotyping, especially in the context of the predominance of incompatible HSC transplantations.

Background. Bloodstream infections (BSI) are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The objective of study was to analyze pre- and post-engraftment BSI.Materials and methods. From January 2018 till May 2021242 patients after first allo-HSCT were enrolled in the study. Median age was 35 (17–65) years. The majority of transplants were done for acute leukemias (71.9 %) in remission (91.7 %) with reduced-intensity conditioning regimens (71.5 %) and peripheral blood stem cells (74.4 %) as a graft source.Results. Of 242 patients 95 (39.2 %) developed BSI: 79 (83.2 %) developed 1 BSI episode, 16 (16.8 %) – 2 or more. Overall 113 BSI episodes were registered: 94 (82.7 %) were caused by single microorganism, 19 (17.3 %) were polymicrobial. Probability of pre-engraftment BSI was 31.0 %, post-engraftment – 11.8 %. In total 134 microorganisms were identified: 61.2 % – gram-negative and 38.8 % – gram-positive bacteria. Gram-negative BSI rate was significantly higher during post-engraftment compared to pre-engraftment phase (57.7 % vs. 70.3 %; р = 0.008). Major risk factor for pre-engraftment BSI was mismatched unrelated allo-HSCTs (hazard ratio (HR) 2.55; 95 % confidence interval (CI) 1.32–4.91; р = 0.03), for post-engraftment BSI – secondary poor graft function (HR 21.70; 95 % CI 7.95–59.24; р

The graft-versus-host disease (GVHD) is among the most common complications after hematopoietic stem cell transplantation (allo-HSCT). The main tools for GVHD prevention remain calcineurin inhibitors (cyclosporin A, tacrolimus), methotrexate, mycophenolate mofetil. Upon implementation of reduced-intensity conditioning regimens, antithymocyte globulin was widely introduced. However, negative effects upon reconstitution of T-cell immunity have been noted, thus increasing risk of severe infectious complications and disease relapse. With extended practice of HSCT from alternative (partially matched or haploidentical) donors, cyclophosphamide was increasingly used. Our aim was to study reconstitution of immune cell subpopulations in the patients undergoing bone marrow transplantation (BMT), when using different GVHD prophylaxis regimens, including the schedules with post-transplant CP usage. The study concerned 44 cases classified into 2 groups. The first one included patients with standard immunosuppressive therapy, antithymocyte therapy, cyclosporine A, methotrexate, mycophenolate mofetil. The second group included the patients who received CP as immunosuppressive drug combined with other treatments (cyclosporine A, methotrexate, mycophenolate mofetil). At specified control terms, (D+14, +30, +60, +90) the blood leukocyte subpopulations were assayed by means of multicolor flow cytometry. Absolute counts of CD4+ cells in HSCT recipients treated with CP post-BMT proved to be sufficiently lower at D+14 and +30, than in those treated with classical immunosuppressive therapy. However, at later terms, (D+60, +90), these differences were not observed. Moreover, in CP-treated bone marrow recipients, absolute numbers of CD8+ cells was significantly higher, compared to the patients who received conventional GVHD prophylaxis. Reconstitution of the studied lymphocyte populations in hematopoietic cell recipients did not depend on the GVHD prophylaxis regimen. Usage of CP combined with bone marrow as a source of stem cells, brings about sufficient decrease of some cell populations (CD4+; CD8+; NK cells) at early terms post-transplant. Administration of CP combined with hematopoietic stem cells as the source of hematopoietic graft seems to be more reasonable.

Aim.Analysis of the effectiveness of the MSCs aministration as the second- or third-line therapy of acute GVHD (aGVHD) resistant to glucocorticosteroid treatment. Materials and methods.The study included 35 patients who received MSCs obtained from the bone marrow of healthy donors as a treatment of steroid-resistant aGVHD. The clinical parameters of patients, MSCs cultural characteristics, the MSC expression profile for various genes including those involved in immunomodulation, expression of cells surface markers, the source of MSCs, as well as the frequency and number of MSC administrations were analyzed. Results.Response to therapy was achieved in 74% of cases, a complete response was reached in 13 (37%) patients, partial response/clinical improvement was demonstrated in 13 (37%). This treatment was ineffective in 9 patients. The prediction of a group of patients with good response to MSC therapy turned to be impossible. The differences between the effective and ineffective for the GVHD treatment MSCs samples were found. The effective ones were characterized with a decreased total MSCs production and an increase in the main histocompatibility complex and PDL-1 antigens expression. Conclusion.These data allow to select optimal samples for aGVHD treatment that can improve clinical results. aGVHD treatment with MSCs has shown efficacy comparable to other treatment approaches. Given the low percentage of complications and the absence of significant adverse effects, MSC therapy seems to be one of the optimal approaches to the treatment of resistant forms of GVHD.

Aim.To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure. Materials and methods.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed. Results.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%. Conclusion.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.

A comprehensive assessment of clinical, clinico-psychopathological, neurological, neuropsychological and instrumental examinations in a single study allows for a more detailed study of cognitive impairments in patients with CSC at a long-term period (12-15 months) after the transplantation of allogeneic hematopoietic stem cells.Purpose. Assessment of cognitive impairments in patients with hematological malignancies at a long-term period after the transplantation of allogeneic hematopoietic stem cells.Materials and methods. Clinical, psychopathological, clinical, psychological, neuropsychological, neurophysiological and neurovisual methods were used to examine 36 patients with various hematological malignancies in the period of 12-15 months after allo-HSCT. Statistical data analysis was performed using the methods of descriptive statistics, analysis of contingency tables and dispersive (with repeated measurements) analysis.Results and discussion. At a long-term period of the study (12-15 months), it was found that cognitive impairments are largely eliminated under the influence of a temporary factor, as well as the treatment of associated conditions (mental disorders, infectious complications, etc.). However, their level does not reach the normal (or close to them) values characteristics of the pre-transplant stage. Among the causes of this phenomenon, mention may be made of the organic lesions of the central nervous system, which are recorded during EEG, CEP, MRI / CT studies, and toxic encephalopathy due to exposure to chemotherapeutic and immunosuppressive drugs.Conclusion. The dynamics of cognitive impairments in general reflects the dynamics of the multifactor effects of various hazards accompanying the transplantation of allogeneic hematopoietic stem cells on the central nervous system. In this case, it can be stated with confidence that the allo-HSCT procedure in the overwhelming majority of cases does not lead to critical cognitive impairments.

In chronic lymphocytic leukemia, the risk of second tumors including hematological malignancies, with which the use of purine nucleosides and alkylating agents in treatment of chronic lymphocytic leukemia is most often associated, is significantly increased. Concurrent detection of this disease and various hematological tumors is a rare occurrence in hematological practice. Use of cytogenetic method or analysis allows to differentiate between 2 tumors and confirm differences in genetic abnormalities in different clones and on different levels of cell differentiation. This article presents a clinical case of simultaneous chronic lymphocytic leukemia and myelodysplastic syndrome with 2 clones with different cytogenetic abnormalities: partial trisomy of chromosome 12 and deletion of the long arm of chromosome 5 formed at different levels of cell differentiation.

The treatment of patients with hematological malignancies is often complicated by a number of negative side effects, which include mental disorders, among which cognitive impairment occupies a special place. Psychopathological, psychological, neuropsychological, neurophysiological and neurovisual methods were used to examine 46 patients with various hematological malignancies during periods prior to allo-HSCT, 1-3 months after allo-HSCT, and 6 months after transplantation. When statistical analysis of data was performed correlation and multivariate analyzes. Patients at each stage of the study identified cognitive impairment caused by a combination of risk factors — the presence of a hematological malignancy, the encephalotropic activity of chemotherapy drugs, and mental, neurological disorders. The characteristic and stable dynamics of CN in the post-transplantation period is traced — a sharp decline in cognitive functions in almost all indicators at once in the early post-transplant period with their gradual recovery by 6 months after allo-HSCT. The attitude of patients to cognitive deficiency also changes during the period of treatment: from anozognosic and hyponozognosic at the pre-transplantation stage to hypernosognostic at long-term periods after allo-HSCT.

The study objective is to investigate the features of subpopulational composition of mobilized hematopoietic stem cells in peripheral blood (PB) and leukocyte concentrates (LC) in adult patients with oncohematological pathology and donors.Materials and methods. In 80 patients with hemoblastoses, expression of CD38, HLA-DR and CD143 (angiotensin-converting enzyme) was measured in PB and LC CD34+CD45low cells. The control group included 10 PB and 14 LC samples from healthy donors. Analysis of PB was performed prior to mobilization of hematopoietic stem cells (HSC) and on the day of leukapheresis prior to HSC collection. LC samples were examined at day 1 after HSC collection.Results. CD143 is expressed on CD34+CD45low cells both prior to mobilization and after it in all patients and donors, but CD34+CD45lowCD143+ cell counts varied depending on diagnosis and mobilization regimen. CD143+ expression on CD34+CD45low cells was significantly higher in patients who received combination of chemotherapy and granulocyte colony-stimulating factor compared to donors and patients with multiple myeloma who received only granulocyte colony-stimulating factor. Along with elevated CD34+CD45low cell count after hematopoiesis stimulation, CD34+CD45lowCD143+ cell counts also increased. It was shown that mobilized HSC almost completely lacks a fraction of early CD34+CD45low progenitor cells not expressing CD38, HLA-DR. Prior to hematopoiesis stimulation among CD34+CD45low cells, CD38+HLADR–cell fractions are prevalent, but after mobilization CD38–HLA-DR+ cell counts increased. No differences between CD34+CD45lowCD143+cell counts in patients with multiple myeloma depending on disease status, sex, age or number of chemotherapy courses prior to HSC mobilizationwere observed.Conclusion. Expression of angiotensin-converting enzyme on CD34+ cells in PB before and after HSC mobilization and in LC was observed. The cell counts varied depending on diagnosis and mobilization regimen.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is being widely applied as a therapy for hematological malignancies. The long-term outcome of allo-HSCT depends directly on the ability of cytotoxic T-lymphocytes to recognize and eliminate the residual tumor. CTLA-4 is one of the regulatory proteins that provide control over the development of the immune response. Polymorphisms in the CTLA4 gene can affect its function and the efficiency of the antitumor response. The objective: to study the effect of non-synonymous single nucleotide polymorphism (nsSNP) c.49A>G in the donor CTLA4 gene on tumor control in the recipient of allogeneic hematopoietic stem cells (HSC). Materials and methods. Donors of HSC were genotyped for nsSNP c.49A>G in the CTLA4 gene by the real-time polymerase chain reaction using the allele-specific primers. Genotyping data was validated by Sanger’s sequencing of 22 randomly selected samples. The overall survival, the event-free survival and relapse probability were calculated using the Kaplan–Mayer method. A log-rank test was used to assess the statistical significance of group disparities. A p-value of 0.05 was considered as significant. Results. The frequencies of the CTLA4 gene c.49A>G polymorphism alleles in the observed population (102 healthy donors of HSC) correspond to the frequencies obtained by the “1000 genomes” project for the European population. The effect of the donor CTLA4 polymorphism on the tumor control was evaluated on the cohort of patients with acute leukemia after human leukocyte antigen (HLA) matched HSCT from an unrelated donor. It was shown, the three-year relapse-free survival was significantly lower for those patients who received grafts from a donor with the homozygous A/A state of nsSNP c.49A>G (p = 0.01), it was 12.7 % versus 62,8 % in group with c.49A>G G/G and A/G donor genotypes. The incidence of relapse was also significantly different for the group with A/A genotype and for the group with G/G or A/G genotypes of the nsSNP and equaled to 83.7 and 29.3 % respectively (p = 0.03). Conclusion. Patients with acute leukemia, who underwent allo-HSCT from unrelated completely HLA-matched donors with c.49A>G G/G or A/G genotypes have the significantly lower risk of relapse than patients whose donors had the A/A genotype. These results suggest practicability of the nsSNP genotyping for the optimal donor selection.

Background . Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal diseases of the hematopoiesis system characterized by dismyelopoiesis and cytopenia, the presence of cytogenetic aberrations and a high risk of transformation into acute myeloid leukemias. Diagnosis of MDS requires a comprehensive approach and mandatory performance of cytological, cytochemical and cytogenetic studies of bone marrow aspirate, as well as histological examination of trephine biopsy. However, in some cases it is necessary to undergo a diagnostic test that would allow verification of the MDS. The study of bone marrow aspirate by multicolor flow cytometry (MFC) can be considered as an additional diagnostic criterion in the diagnosis of MDS.The objective of the study was to estimate the incidence of myelodysplastic features in patients with various forms of MDS by the MFC method. Materials and methods . The study included 79 patients with MDS: 8 with MDS with 5q deletion, 33 with MDS without excess blast cells and 38 with excess of blasts. A bone marrow aspirate test was performed by 6-color flow cytometry. The control group included 35 donors of allogeneic bone marrow. The analysis resulted in a conclusion on the Ogata score scale, the Wells prognostic scale and the combined Ogata–Wells scale. When using the screening method, the presence of two or more cytometric signs of MDS was detected in 60 (75.9 %) of 79 MDS patients. Wells score was higher in MDS group with an excess of blast than in others. Using the combined Ogata–Wells scale, cytometric aberrations were found in 70 (88.6 %) of 79 MDS patients. In patients with MDS with an excess of blasts, the incidence of increased CD34+ and/or CD117+ myeloid cells was higher than in MDS patients without an excess of blasts and an MDS with a 5q deletion. The frequency of abnormal cytometric parameters (anomalous expression of CD34, CD117, CD56+ myeloblasts) in these groups did not differ. In patients with isolated 5q deletion and MDS without excess of blasts, an increased proportion of CD7+CD34+ cells was more often detected than in MDS with an excess of blasts.Conclusion . Thus, cytometric abnormalities in MDS are common, even in patients without excess of blasts. The MFC method can be used as an additional diagnostic method in the initial diagnosis of MDS.

Introduction. An accepted fact in allogeneic hematopoietic stem cells transplantation (allo-HSCT) from unrelated donors is that matching for HLA genes is critical to ensure the best outcomes for patients. The current gold standard is an unrelated donor matched for 10/10 HLA alleles (HLA-A, -B, -C, -DRB1, -DQB1). In the HLA-mismatched setting graft-versus-host disease (GVHD) is increased, and overall survival becomes significantly worse. The importance of HLA-DPB1matching is more controversial.The aim of our study was to evaluate the impact of HLA-DPB1 mismatches on outcome of patients who underwent 10/10 HLA matched unrelated HSCT.Materials and methods. 49 patients treated with allo-HSCT in transplant center of National Research Center for Hematology from 10/10 HLA-matched unrelated donors were included in the study. High-resolution typing for HLA-DPB1 was done by PCR with sequence specific primers (SSP) using Olerup typing kits. HLA-DPB1 permissive/nonpermissive mismatches were examined according to TCE groups. Overall survival, event-free survival and survival without acute graft-versus-host disease were calculated by Kaplan–Meier method, and compared with log-rank test. Proportional hazard Cox models were used for multivariate analysis.Results. The 3-year overall survival after allo-HSCT was 68 %, event-free survival – 51 %, acute GVHD-free survival – 62 %. No significant impacts of HLA-DPB1 disparities on overall, event-free survival and probability of acute graft-versus-host disease were observed. Patients with nonpermissive HLA-DPB1-incompatible donors had a tendency to increased event-free survival. The factors significantly increasing risk of acute GVHD were peripheral blood grafts, advanced-stage disease and male gender of recipients.Conclusion. The factors associated with acute GVHD are peripheral blood grafts, advanced-stage disease and male sex of recipients. For more precise evaluation of impact of HLA-DPB1-incompatibility on results of allo-HSCT further investigations are needed.

A wide range of toxic complications of BCR-ABL tyrosine kinase inhibitors therapy due to non-targeted inhibition of other protein kinases. This is of particular importance in the treatment of patients with Ph-positive lymphoblastic leukemia, who receive, in addition to tyrosine kinase inhibitors, cytotoxic drugs, enhancing myelotoxicity and, as a consequence, infections and thrombo-hemorrhagic complications. In addition, complex inter-drug interactions lead to the manifestations of combined toxicity. This article presents a case report of patient with relapsed acute Ph-positive lymphoblastic leukemia, treatment of which was accompanied by numerous complications, especially during treatment of II and III generation tyrosine kinases inhibitors.

The frequency of achieving complete remission, as well as overall and disease-free survival, in multiple myeloma (MM) had increased due to introduction in MM treatment regimens of high-dose chemotherapy with following autologous hematopoietic stem cell transplantation (ASCT). However the number of relapses remains high, caused by persistence of residual tumor cells, i.e., the presence of minimal residual disease (MRD). One of the methods for MRD study is multicolor flow cytometry (MFC) where abnormal expression of surface antigens on myeloma plasma cells (PC) is determined. The aim of our study was to investigate the MRD by MFC before and after ASCT, the frequency of MRD-negative status achievement in complete remission (CR) patients at +100 days after ASCT and the frequency of abnormal expressed antigens on myeloma plasma cells. The study included40 MMpatients in CR at +100 days after ASCT and showed that the most common aberrations of PC were: abnormal absence of CD19 and/or CD27, decreased expression of CD38 and abnormal presence of CD56. The proportion of myeloma PCs from all bone marrow cells decreased significantly after ASCT: 20 % of patients acquired MRD-negative status, 10 % had a decrease in the number of abnormal PCs by one fold. Analysis of probability of immunochemical relapse showed that the worst prognosis was in patients with MRD-positive status before and after ASCT. During the MRD monitoring within 3-18 months, MRD-relapses were detected with the subsequent development of immunochemical relapse. The detection MRD in the dynamics is more informative than the study at only one step of therapy. It may help to select more adequate treatment for patient with multiple myeloma in each specific case.

From 2001 to 2013 eleven patients with relapsed acute promyelocytic leukemia (APL) (median age – 30 years) received arsenicum trioxide (ATO). ATO was administered as a 2nd line relapse therapy in 9 patients, as 1st line relapse therapy in 2 patients. ATO was administered in a dose of 0.1 mg/kg in 7 patients, 0.15 mg/kg – in 4 patients. The induction duration was 14 days in 3 patients, 24–35 days in 2 patients, 60 days in 6 patients. From the 1st day of ATO patients received 45 mg/m2 all trans retinoic acid (ATRA) (1 patient – from day 29 of ATO therapy). Maintenance therapy ATO + ATRA (10–14 days courses, every four weeks) patients were receiving during 10–15 months. 2 from 3 patients with molecular relapses achieved remission lasting 57 and 89 months after the 14-day ATO courses. 1 from 2 patients with bone marrow relapse achieved remission lasting 27 months after the 24–35-day ATO courses. 60-day courses were effective in 5 of 6 patients: in 4 of which remission are retained during 16, 19, 27, 57 months; 1 patient was relapsed after 12 months; 1 patient did not achieve molecular remission. 3 patients received allogeneic hematopoietic stem cell transplantation (alloHSCT), 2 of which alive in remission. 1 patient received autologous hematopoietic stem cell transplantation in the 2nd molecular remission (alive in remission). 4 patients died: 1 – in the 3rd relapse (duration of 2nd remission – 9 months), 1 – in remission from complications after alloHSCT, 1 – from APL progression, 1 – sudden death in 2nd remission lasting 72 months. ATO + ATRA for 60 days with supportive therapy are more effective than chemotherapy in the treatment of APL relapse. Interferon α + ATRA are inappropriate treatment of APL molecular and cytogenetic relapse. Using autologous HSCT in 2nd molecular remission will improve the results of APL relapse treatment.

An interim analysis of long-term treatment results for 202 patients with acute lymphoblastic leukemia (ALL), aged 15–60 years, received therapy according protocol ALL-2009 was shown. The basic principle of ALL-2009 was non-aggressive, but continued cytostatic exposure, as well as the reproducibility in a regional hematology centers. Long-term treatment results of ALL-2009 are 2 times higher than the previously obtained in adult ALL patients within the Russian clinical multicenter studies of adult ALL. The 5‑year overall survival of patients younger than 30 years was 73.6 %, relapse-free survival (RFS) – 71.5 %, compared with 52.7 % and 61.8 % in patients aged 30 years and older, respectively. In patients with B-precursor ALL with normal karyotype of blast cells significantly higher 5‑year RFS (82.1 %) compared to patients with abnormal karyotype (58.8 %) was registered. For T-ALL cytogenetic characteristics of blast cells had no prognostic significance. For patients with T-ALL important to perform autologous stem cell transplantation as a later consolidation, as this significantly reducerelapse rate (from 33 to 0 %).