Search

Aim. To study the risk factors, symptoms and outcomes of candidemia caused by C. albicans and C. non - albicans in patients with hematological malignancies. Materials and methods. The study included patients with hematological malignancies and candidemia. The diagnosis of candidemia was established according to the single isolation of Candida spp. from blood culture and the presence of symptoms of infection. Results and discussion. Over 12 years (2006-2017), candidemia was diagnosed in 75 patients aged 17 to 77 years (median 48 years). The causative agents of candidemia were C. albicans in 34.7% of patients, C. non - albicans - in 65.3%. Candidemia caused by C. albicans prevailed in patients of the older age group (median 56.5 years, p=0.04) and in patients with lymphoma (61.5%, p=0.01) with colonization of the gut by the same species of Candida (88.5%, p=0.002). Isolation of C. non - albicans from blood culture was more common in patients with acute leukemia (51%, p=0.01) and in recipients of allogeneic hematopoietic stem cells (22.5%, p=0.01). The ability to form biofilms was observed more frequently among C. non - albicans (59.2%) than C. albicans (19.2%, p=0.001). The clinical symptoms of candidemia were non - specific (fever was in 97%). Septic shock developed in 25 (33%) patients with comparable frequency in both groups. Concomitant infections was also comparable (73% vs. 73.5%). Overall 30-day survival in patients with candidemia caused by C. albicans and C. non - albicans was 61.2% and 61.5%. Treatment with echinocandin was associated with increase of survival compared to other antifungal agents among patients with C. albicans candidaemia (88.9% versus 40%, p=0.02) and among C. non - albicans (77.3% versus 47.8%). Conclusion. C. non - albicans constituted a high proportion among causative agents of candidemia. High mortality rate was observed in both groups. Initial therapy with echinocandin was associated with increase of survival.

The paper describes the results of 15 consecutive Russian clinical trials in the treatment of different types of acute leukemias, conducted by Russian cooperative group within the last 27-years and included more than 25 hundred patients. It was shown that the 5-years overall survival in AML younger than 60 years patients improved from 20 to 33%, in ALL - from 38 to 65%, in APL - from 0 to 95%. The cooperative work resulted in balanced clinical recommendations and protocols, reproducible in regional hospitals. Though till now there is a big difference in the long term outcome in acute leukemias patients treated in coordinating or regional centers mostly due to much higher early death rate: 7.5-9.5% vs 18-25%. This parameter should be used as criteria of the total efficacy of hematological service in each region of Russia. It became possible within the last years to integrate the minimal residual disease monitoring into clinical trials thus providing a clue parameter for choosing the further therapy - allogeneic stem cell transplantation. Non - chemotherapeutic approach with arsenic trioxide and all - trans retinoid acid had dramatically changed the toxicity and duration of treatment with very high efficacy. The Russian cooperative group was the first that started to include pregnant women with acute leukemias into clinical trials. This prospective and prolonged experience has shown that pregnancy in acute myeloid leukemia is an extremely poor prognostic factor, but it does not influence the outcome in acute lymphoblastic leukemia.

Aim: to compare the results of tumor visualization when using 18F-FDG and 11C-methionine PET/CT after auto-HSCT in MM patients. Materials and methods. A prospective study included 27 MM patients subjected to 18F-FDG and 11C-methionine PET/CT on day 100 after auto-HSCT. Obtained images were visually and semi - quantitatively analyzed. Focal areas of increased uptake for every radiopharmaceutical agent (hypermetabolic foci) not associated with its physiological distribution were registered. Maximum Standardized Uptake Values (SUVmax) in pathological foci were automatically calculated for every radiopharmaceutical agent separately. PET/CT findings were compared to antitumor response achieved after auto-HSCT according to International MM Working Group criteria. Results. After auto-HSCT, the majority of patients (16/60%) achieved a complete response. Abnormal 18F-FDG uptake was registered in 37% (n=10) of patients, negative PET findings were obtained in 63% (n=17) of patients. 11C-methionine PET/CT revealed hypermetabolic foci in 67% (n=18) of patients, and there was no 11C-methionine uptake in 33% (n=9). Pathological foci of radiopharmaceutical agent uptake were 1.8 times more frequently revealed using PET/CT with 11C-methionine (p

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

Mediastinal gray-zone lymphoma (MGZL, lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma) was declared as a separate entity in WHO classification of Tumors of Haematopoetic and Lymphoid Tissues in 2008 and 2017 years. Despite of similar pathomorphological characteristics between primary mediastinal B-cell lymphoma and Hodgkin lymphoma, clinical features and optimal therapeutic approach to MGZL are not clearly defined. Usually MGZL manifests with mediastinal lymphadenopathy, although extranodal lesions often occur (grey-zone lymphoma, GZL). Patients with MGZL have unfavorable prognosis, taking into account high rate of relapse. This article describes two cases of MGZL. First case manifested by arrhythmias due to primary heart involvement. In spite of cardiac failure antracycline-containing chemotherapy (6 courses of R-DA-EPOCH) it allowed to achieve a complete remission and resolving of arrhythmias. Second case was represented by metachronous tumors: primary mediastinal B-cell lymphoma at the time of disease onset and classical Hodgkin lymphoma, NS II, diagnosed after disease progression. Thus, we demonstrated two examples of MGZL that differ by clinical manifestation, response to chemotherapy, which emphasizes an importance of pathogenesis studying, and using of new therapeutic approaches.

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.

Purpose of the study. A comparative evaluation of the effectiveness of different therapeutic strategies in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Materials and methods. Patients with PV or ET, diagnosed according to the criteria WHO 2016 were included in the study. The primary endpoint - 6 months of therapy (clinical-hematological and molecular responses). The secondary endpoint - 12 months of therapy (clinico-hematologic, molecular, histological responses). Sixty three patients were included in the analysis: the first group consisted of 33 patients who received the therapy with ce-pegiterferone alpha-2b (ce-pegalpha-INF-α-2b), 10 of them received previous treatment; the second group - 23 patients btained hydroxycarbamide; the third group - 7 patients were treated with recombinant interferon alpha therapy (rINFα). In comparison groups, differences in age were revealed: patients receiving hydroxycarbamide therapy were older. Phlebotomy occurred in 36% of patients in the first group, 9% in the second group, and 14% in the third group. Results. By the 6th month of therapy, 43% of the patients receiving the ce-pegalpha-INF-α-2b had complete clinical-hematologic response, 36% had partial clinical-hematologic remission and stabilization of the disease was established in 21% cases. No disease progression occured. By the 12th month of therapy, statistically significant differences in terms of efficacy between the different therapeutic groups (p = 0.2462, Fisher's exact test). In all three groups, the allelic load of JAK2V617F decreased: from 50 to 19%, from 22.3 to 15.8%, from 50 to 7.19%, respectively. The lower the allele load positively correlated with better response to therapy, which was observed in all analyzed groups. Hematologic adverse events (AEs) were more frequently observed in patients receiving ce-pegalpha-INF-α-2b therapy. Local reactions developed on 3-7 days of therapy as a hyperemic macula at the injection site. Both these reactions and hair loss did not influence on patient’s condition. In the second group (patients with hydroxycarbamide therapy) there were changes in the skin and mucous membranes: dry skin, stomatitis, and in older patients new keratomas appeared. The flu-like syndrome was the most common adverse event associated with the therapy of ce-pegalpha-INF-α-2b, which fully relived during the first month of therapy. There was only one case with the flu-like syndrome we observed at the 11th month of therapy. As a rule, the biochemical blood test changes did not influence on patient’s condition, were mostly associated with dietary violations, had a tendency to self-resolution and did not require medical interventions. Serious AEs were reported in one case - pulmonary embolism in a patient treated with rINFα. The reasons for the therapy discontinue in group 1: toxic hepatitis, intolerance, by the request of the patient, inadequate efficacy of therapy; in group 2: skin toxicity, in group 3: thromboses. The conclusion. Treatment of ce-pegalpha-INF-α-2b in patients with PV and ET is highly effective - the most patients pbtained clinical and hematological responses. There were no statistically significant differences in these parameters in comparison with hydroxycarbamide and rINFα. The use of the ce-pegalpha-INF-α-2b had an acceptable safety profile. The estimated therapeutic dose should be calculated according to body weight. To reduce the frequency of hematologic AE, titration of the drug dose is required.

B-cell acute lymphoblastic leukemia (B-ALL) is a diverse group of malignant blood disorders both with regard to the biological properties of the tumor and to therapeutic approaches. Immunophenotyping, molecular genetic techniques, whole-genome sequencing characterize B-ALL as a very diverse group for sensitivity to chemotherapy and prognosis. We present three clinical cases of patients with B-ALL and expected good response to standard therapy, in whom standard protocol treatment failured: refractoriness, persistence of minimal residual disease (MRD), and progression (MRD increase). The remission in these patients was achieved after chemotherapy change to immunological targeted therapy. Nowadays a unified therapeutic approach to all primary patients of the B-ALL is considered generally outdated. Great efforts are carrying out to develop molecular genetic classifications. The molecular dissection of subtypes of B-ALL goes on, and new protocols for selective treatment with targeting are clearly outlined for each subtype of B-ALL.

Objective. To evaluate occurrence, variety, structural peculiarities and prognostic meaning of cytogenetic abnormalities in adult patients with Ph-negative acute lymphoblastic leukemia (ALL) receiving therapy according to ALL-2009 protocol. Materials and methods. The study included 115 adult patients with firstly diagnosed Ph-negative ALL: 58 male and 57 female aged from 15 to 61 years (mean age 26.5 years), who underwent treatment from September 2009 to September 2015 in National Medical Research Center for Hematology MH RF (n=101) and in hematology departments of regional hospitals (n=14). All patients received therapy of ALL-2009 protocol (ClinicalTrials.gov, NCT01193933). The median follow-up was 24.5 months (0.2-94.4 months). As a part of the study results of a standard cytogenetic assay (SCA) were analyzed and fluorescence hybridization in situ (FISH) with the use of DNA-probes was performed on archived biological material for structural changes in gene locuses MLL/t(11q23), с-MYC/t(8q24), TP53/ deletion 17p13, CDKN2A/ deletion 9p21, translocation t(1;19)/E2A-PBX1 и t(12;21)/ETV6-RUNX1; iAMP21 identification. Results. Karyotype was defined using SCA in 86% of patients. Normal karyotype was found in 48.5% of them, chromosome aberrations in 51.5% (structural changes were found in 19.2%, hyperploidy in 27.2%, and hypoploidy in 5.1%). In 17.2% of patients complex karyotype abnormalities were found. With the use of FISH technique aberrations were found in 67% of patients: 9p21/CDKN2A deletion in 24.3%, MLL/t(11q23) gene abnormalities in 7.8%, 17p13/TP53 deletion in 5.2%, abnormalities of c-MYC/t(8q24) in 1.7%, t(1;19)/E2A-PBX1 in 0.8%, and iAMP21 in 0.8%, other abnormalities (additional signals/absence of signals from gene locuses) in 26.4%, t(12;21)/ETV6-RUNX1 was not found. FISH technique use in addition to SCA allows to increase aberrant karyotype location from 51.5 to 67%. A statistically significant correlation of 9p21/CDKN2A deletion with high serum lactate dehydrogenase activity (p=0.02); MLL/t(11q23) gene abnormalities - with leucocytosis and high blast cells level in blood (p=0.0016), hyperploidy - with normal leukocyte count (p=0.02) was shown. In groups with different cytogenetic abnormalities no statistically significant differences of treatment with ALL-2009 protocol were found (in terms of complete remission, early mortality and treatment resistance). When connection of cytogenetic abnormalities and their combinations with long-term results were analyzed according to ALL-2009 protocol, only two characteristics - MLL/t(11q23) and c MYC/t(8q24) gene abnormalities had a statistically significant influence on disease-free survival (HR - 176.9; p

Nodal anaplastic ALK-negative large cell lymphoma (nALCL, ALK-) is a Т-cell lymphoma that is characterized by aggressive clinical course and low sensitivity to СНОР (cyclophosphamide, doxorubicin, vincristine, prednisolone) and other chemotherapy regimen. In the article we present a literature review and describe our clinical case of nALCL, ALK-. For the first time a combination of Brentuximab vedotin with modified program NHL-BFM-90 was used as a first-line therapy. As a result of immunochemotherapy a complete antineoplastic effect was obtained. For consolidation of this effect high-dose chemotherapy with following autologous blood stem cell transplantation was performed. The chosen treatment tactics allowed to achieve a complete remission in a medium risk group patient.

Contex. Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkins lymphoma, characterized by generalized lymphadenopathy, hepatosplenomegaly and dysproteinemia. Hypergammaglobulinaemia is revealed in 50-83% pts with AITL. However, the characteristics of immunoglobulinopathies observed in AITL are scarce. Objective: The aim of the study was to characterize quantitative and qualitative immunoglobulinopathies in patients with AITL at the onset of the disease. Patients and methods. 55 patients with newly diagnosed AITL were enrolled in the study, the male/female ratio was 30/25; median age was 61 (29-81) years. Diagnosis was based on standard WHO criteria. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay. Results. Quantitative and qualitative immunoglobulinopathies were determined in 49 (89,1%) of 55 pts. Quantitative immunoglobulinopathies were revealed in 47 (85.5%) of 55 cases, qualitative - in 14 (25,5%). Combination quantitative and qualitative immunoglobulinopathies was observed in 12 (21,8%) of 55 pts. The detected immunoglobulinopathies were divided into 4 groups: polyclonal hypergammaglobulinaemia, hypogammaglobulinaemia, oligoclonal gammapathy, and monoclonal gammapathy. Polyclonal hypergammaglobulinaemia was marked in 41 (74.5%) of 55 pts, elevated level of IgG was determined in 27 (49,15%) of 55 cases, IgM - in 18 (32,7%) and IgA - in 21 (38.2%). Interestingly, polyclonal IgE hypergammaglobulinaemia was detected in 12 (48,0%) of 25 cases of performed studies. Hypogammaglobulinaemia was detected in 8 (14,5%) of 55 cases. Oligoclonal gammapathy was determined in 4 (7.3%) of 55 pts. Monoclonal gammapathy was revealed in 11 (20,0%) of 55 cases. The amount of monoclonal immunoglobulin varied from 2.6 to 14.1 g/l. Monoclonal immunoglobulin Gk was detected in 5 of 11 pts, Gλ - in 2, Mλ - in 2, Mk - in 2. Monoclonal gammapathy was accompanied by polyclonal hypergammaglobulinaemia in 9 of 11 cases, hypogammaglobulinaemia - in 2. Conclusions. Quantitative and qualitative immunoglobulinopathies are observed in most patients at the onset of AITL. Quantitative abnormalities were determined more often than qualitative. Monoclonal gammapathy can be a manifestation of lymphoproliferation and other concomitant disorders. The prognostic value of immunochemical parameters is still unclear and requires dynamic observation and study.

Aim. To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. Subjects and methods. The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year’s duration were adverse events, pregnancy, and patients’ decision. Information was collected retrospectively and prospectively in 2008-2016. Results. The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. Conclusion. Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.

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.

Primary central nervous system (CNS) lymphomas account for 13-20% of the posttransplant lymphoproliferative disorders (PTLD) and rank among the most aggressive conditions. Reduction of immunosuppressive therapy should be mandatory to treat PTLD, but this is rarely used as the only therapy option. Chemotherapy regimens for PTLD involving the CNS most commonly include high-dose rituximab and high-dose methotrexate and/or cytarabine. The efficiency only of discontinuation of immunosuppressive therapy for PTLD does not exceed 5—10%, but there are no literature data on its efficiency for PTLD involving the CNS. The paper describes a clinical case of achieving long-term remission in a female patient with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma involving the central nervous system, associated with immunosuppression after kidney transplantation from a related donor, in the absence of chemotherapy during immunosuppressive therapy discontinuation and transplantectomy.

The paper describes 4 clinical cases of thrombotic events (pulmonary embolism, deep vein thrombophlebitis, acute myocardial infarction, ischemic stroke) that have occurred in patients with hemophilia. It discusses the possible causes of their development and methods for their prevention and treatment. Controlled natural hypocoagulation, in which the dose of an administered deficient factor decreases to such an extent that in order to maintain the safe level of hypocoagulation (plasma factor activity is 15—20%; activated partial thromboplastin time is 1.5—2 times normal values), is proposed as one of the treatment options.

Breast implant-associated anaplastic large-cell lymphoma will be identified as a separate nosological entity in the 2017 adapted WHO classification due to differences in its clinical presentations, pathogenesis, and prognosis with those of nodal and cutaneous anaplastic large-cell lymphomas. The paper gives a review of the literature and describes the authors’ own clinical case of common breast implant-associated anaplastic large-cell lymphoma involving breast tissue, axillary lymph nodes, anterior chest muscles, and bone marrow. The treatment policy chosen by the authors could achieve complete remission.

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.

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 analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells). Subjects and methods. The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in 9.4·109/l (0.4-899.0), lactate dehydrogenase in 901 IU (31-13 059), an initial central nervous system lesion in 17 (8.7%), mediastinal injury in 3 (1.5%), and splenomegaly in 111 (57.2%). The results of standard cytogenetic analysis are known in 113 (60.4%) patients. Normal karyotypes were detected in 49 (54.5%) out of the patients; t(4;11) in 9 (5.4%), t(1;19) in 2 (1.2%), and other karyotypic abnormalities in 53 (46.9%). Thirteen (7.8%) patients underwent allogeneic hematopoietic stem cell transplantation in first complete remission (CR); their proportion did not differ in the federal and regional centers. Results. The frequency of CR achievement was the same in the federal and regional centers and generally amounted to 87.5%. Early (8.8%) and CR (9.6%) mortality rates remained high despite the low aggressiveness of cytotoxic action, necessitating the improvement of auxiliary treatment. The five-year overall survival (OS) rates vary considerably in the federal and regional centers (72.6 and 43.8%), the relapse-free survival (RFS) (70.2 and 53.4%) and recurrence risk (23.1 and 36.5%) are comparable. This suggests that the non-intensive, but continuous exposure principle built in the ALL-2009 protocol makes it possible to reproduce the envisaged treatment program and to achieve satisfactory results. Conclusion. The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.

Aim. To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). Subjects and methods. In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC. Induction therapy with bortezomib-containing cycles was performed. Autologous stem cell transplantation was carried out in 48 patients. The median follow-up of patients was 19.3 months (3.2—77.4 months). Disease progression was diagnosed in 69 (51.5%) patients; 12 patients also underwent FISH study during disease progression. Results. At the onset of MM, amp1q21 was detected in 53 (39.6%) patients. The overall 5-year survival rate in patients with amp1q21 was almost 2 times lower than that in those without amp1q21 (43.5 and 79.4%, respectively; p=0.07). The overall 5-year survival rate in patients with one extra copy of 1q21 (only 3 copies) was 67.3%, that in those with 2 or more extra copies of 1q21 (only 4—7 copies) was 20.9% (p=0.0016). Nine (75%) of the 12 patients examined during disease progression were found to have amp1q21: 2 cases were detected in the period of progression to have amp1q21 in its absence at disease onset; 7 cases had amp1q21 both at MM onset and progression; however, the number of copies of 1q21 was unchanged. Conclusion. Аmp1q21 is one of the most common chromosomal abnormalities in patients with new-onset MM and may appear in the course of disease progression. The presence of аmp1q21 is an important prognostic factor and must have to be included in the diagnostic study both at disease onset and progression.

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.

Aim. To provide the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) with monoclonal immunoglobulin secretion and to evaluate the efficiency of intensified mNHL-BFM-90 or R-DA-EPOCH/R-HMA therapy programs in patients with Ig-secreting DLBCL. Subjects and methods. A clinical trial was conducted in 93 patients with newly diagnosed DLBCL, among whom 21 (22.6%) were found to have monoclonal immunoglobulin secretion. Results. Ig-secreting DLBCL is shown to be characterized by bone marrow involvement (p

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 estimate the spread of weak D antigen types of the Rhesus system in the citizens of the Russian Federation and a possibility of serologically identifying these types. Subjects and methods. The red blood cells and DNA of people with weakened expression of D antigen were investigated using erythrocyte agglutination reaction in salt medium (2 methods); agglutination reaction in the gel columns containing IgM + IgG anti-D antibodies, indirect antiglobulin test with IgG anti-D antibodies (2 methods); polymerase chain reaction to establish the type of weak D. Results. A rhesus phenotype was determined in 5100 people in 2014-2015. The weakened agglutinable properties of red blood cells were detected in 102 (2%) examinees. 63 examinees underwent genotyping to identify the variants of the weak D antigen, which identified 6 weak D types. There were the most common weak D types 3 (n=31 (49.2%)) and weak D type 1 (n=18 (28.6%)), including weak D type 1.1 in one (1.6%) case. The other 4 weak D antigen types were as follows: weak D type 2 (14.3% (n=9)), weak D type 15 (4.8% (n=3)), weak D type 4.2 (DAR) (1.6% (n=1)) and weak D type 6 (1.6% (n=1)). The antiglobulin test in the gel column containing antiglobulin serum was the most sensitive serological assay to identify the weak D antigen. Only a molecular test could establish weak D type 15 in 2 samples of red blood cells with Ccdee and ccdEe phenotypes. Conclusion. The weak D antigen could be serologically identified in 96.8% of cases. When testing for weak D, particular attention should be given to people with the D-negative phenotype who had the C or E antigens. Our investigations conducted for the first time in Russia will be able to improve the immunological safety of red blood cell-containing medium transfusions for patients.

Aim. To generalize hematologists’ experience of the diagnosis and differential diagnosis of splenic red pulp lymphoma (SRPL). Materials and methods. Eighty-seven splenic biopsy specimens taken from patients with different B-cell lymphoproliferative diseases were examined in the Hematology Research Center in 2013—2014. The diagnosis of SRPL was based on the morphological, immunohistochemical, immunophenotypic, and molecular examinations of the splenic biopsy specimens, blood and bone marrow (BM) tests in 4 (4.6%) cases. Results. There was significant splenomegaly in all SRPL cases, lymphocytosis in 56 to 94% (leukocytes, 55 and 75·109/l in 2 cases), circulation of hairy lymphocytes with the phenotypes CD20+ (markedly), CD11c+/±, CD103+/± (weakly), LAIR-1+, CD25–, CD5–, CD10–, and CD23–, which did not contain tartate-resistant acid phosphatase, without BRAFV600E mutation, BM with insignificant lymphoid infiltration of CD20+, CD25–, Annexin 1–, and Cyclin D1–. The weight of the spleen averaged 3900 g (1450-9500 g); its tissue exhibited lymphoid infiltration of the red pulp with the phenotypes CD20+, DBA.44+, CD25–, Annexin1–, Cyclin D1–, CD103–, CD123–, CD27–, focal СD11c±, and TRAP±. Four patients (2 after splenectomy (SE) and 2 after SE and chemotherapy with cladribine and rituximab) are being followed up in remission. Conclusion. SRPL is a rare disease that should be presumed to be in significant splenomegaly and lymphocytosis with hairy lymphocytes, which have only some markers for classical hairy cell leukemia (HCL), in minor BM lesion. SE is the standard for diagnosis and treatment. The differential diagnosis of SRPL with HCL has clear criteria and that with HCL-v is undetected.

The described case of FIP1L1-PDGFRА-positive myeloproliferative disease is characterized by an atypical aggressive course to develop severe specific complications as injuries to the brain, heart, lung, and intestine. Pathogenetic therapy with imatinib could stabilize a patient’s state, but failed to produce a complete hematological response. Switching from imatinib to dasatinib could produce sustained clinical, hematological, and molecular remissions.

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 study the clinical features of Castleman’s disease (CD) and to elaborate therapeutic approaches in its different morphological types. Subjects and methods. The clinical and laboratory data were studied in 59 prospectively examined patients and 17 retrospectively examined ones with CD who had been treated at the Outpatient Department, Hematology Research Centre, in 1996 to 2014. There were a total of 37 men (median age, 36 years) and 39 women (median age, 34 years). The diagnosis was established from the results of histological and immunohistochemical examinations of removed lymph nodes (LN) or tumors in all the cases. Results. A hyaline vascular variant (HVV) with local LN involvement was diagnosed in 38 (50%) patients; a plasma cell variant (PCV) was in 38 (50%); among the latter, 17 (22%) patients were found to have local involvement and 21 (28%) had generalized (multicentric) involvement (multicentric Castleman’s diseases (MCD)). Five (24%) patients with MCD were established to be infected with human herpesvirus type 8 (HHV-8). HVV was more frequently diagnosed in women (4%) than in men (29%); PCV was equally common in both men (47%) and women (53%); MCD was statistically significantly more frequently encountered in men (86%) than in women (14%) (p=0.05). The basic involvement areas in local HVV and PCV were peripheral (38%), mediastinal (29), retroperitoneal (18%), abdominal (9%), and small pelvic (6%) LNs. HVV and local PCV were benign and these were cured by surgical removal of LNs involved in the pathological process. MCD took its aggressive course with obvious constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, hypergammaglobulinemia, autoimmune hemolysis, thrombocytopenia, and involvement of extranodal foci in the pathological process. MCD transformation to plasmablastic lymphoma was observed in 4 of the 5 HHV8-positive patients and followed by a poor outcome. The prognosis of untreated MCD was unfavorable. In a number of cases prednisolone monotherapy worsened prognosis and the MCD patients receiving timely multiple-drug R-CHOP or R-VD chemotherapy could achieve sustained remission (the 5-year overall survival was 55%). Conclusion. CD must be included into the differential diagnosis of lymphadenopathies. When specific treatment is performed, the prognosis of HVV and local PCV is favorable: the disease is surgically cured in 95% of cases. Multidrug chemotherapy according to the B-cell lymphoproliferative disease program is indicated for the treatment of MCD: sustained remission can be achieved by the use of R-CHOP or R-VD programs. The HHV-8-positive variants of MCD increase the probability of transforming the disease to incurable plasmablastic lymphoma. Overall, prognosis and therapy choice in HIV-negative patients with CD depend on the histological variant of the disease, the extent of a tumor, and HHV-8 infection.

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 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 determine the immunoglobulin variable heavy chain (IgVH) genes and their somatic mutations and to compare these data with the clinical and laboratory parameters of patients and the outcomes of the disease. Subjects and methods. The investigation enrolled 24 patients (9 men and 15 women whose age was 32 to 77 years (median age, 60 years) with splenic marginal zone B-cell lymphoma (SMZBCL). The latter was diagnosed on the basis of histological and immunohistochemical examinations of a bone marrow trephine biopsy specimen, immunophenotyping of peripheral lymphoid cells or bone marrow aspirates. Results. The mutational status of the IgVH genes was analyzed in all the 24 patients. It was found that the tumor cells contained mutated IgVH genes (the VH1-family genes participated in most cases) in 15 (62.5%) patients with SMZBCL and unmutated ones in 9 (37.5%). There was a tendency towards more common tumor progression in patients with unmutated IgVH genes than in those with mutated ones. Conclusion. The presence of SMZBCL cases with both mutated and unmutated IgVH genes and the higher frequency of the VH1-2 gene are likely to indicate the molecular heterogeneity of the origin of this lymphoma.

Russian Interregional Register of hematopoietic stem cell transplantation was established in 2000. 11 transplant centres from 7 Russian cities are including in Register now. In this analysis we applied transplant activity survey data from 01.01.1996 to 31.12.2006. A total 1118 transplants (846 – autologous and 272 – allogeneic) were carried during this period.

Tumor-associated genes (PRAME, WT1 and XIAP) expression study is conducted in 34 patients with multiple myeloma (MM) in disease onset and after chemotherapy (VAD, 20 pts) and proteosom inhibitor therapy (10 pts). PRAME, WT1 и XIAP gene expression in bone marrow cells detected by polymerase chain reaction (PCR) method. PRAME gene expression in 62% primary patients was revealed, thus expression median was 0.3% that almost in 100 times greater than in bone marrow donors (0.0035%). WT1 gene expression in 20% patients was detected, and it was determined only in PRAMEpositive patients. At diagnosis XIAP gene expression was revealed in all MM patients, thus expression median was more 10 times greater than in the control groups (28% versus 2%). In patients with PRAME hyperexpression partial response was achieved only in 25% of cases, while in patients with low or absence of PRAME expression VAD therapy was effective in 75% of cases (р=0,06). After bortezomib treatment XIAP gene expression level was significantly decreased with complete and partial remission achievement: from 11-325% (median – 66%) to 1-123% (median – 20%). In cases of tumor resistance to bortezomib treatment XIAP expression increased from 16-127% (median – 36%) to 22-528% (median – 121%).

Cytomegalovirus infection is one of the critical and life-threatening infectious complications in patients after allogeneic hematopoietic stem cell transplantation. The most significant risk factors for the development of cytomegalovirus infection are cytomegalovirus serostatus of the donor and recipient and delayed reconstitution of cytomegalovirus-specific CD4+ and CD8+ T lymphocytes after allogeneic hematopoietic stem cells transplantation.The infection may be asymptomatic or may lead to serious complications such as cytomegalovirus disease, which happens in 10-40% of cases. Cytomegalovirus infection has different impact on patients after hematopoietic stem cell transplantation. For instance, acute and chronic graft versus host disease may also be the risk factors for the development of cytomegalovirus infection. There is also information about the influence of cytomegalovirus infection on a graft failure. We also know that cytomegalovirus replication is associated with lower relapse risk in patients with acute myeloid leukemia and chronic myeloid leukemia.Antiviral prophylaxis and preemptive therapy are good strategies to reduce the risk of the cytomegalovirus infection. Despite this, cytomegalovirus infection is still associated with decreased overall survival and increased non-relapse mortality in recipients of allogeneic stem cells.The aim of this review is to systematize modern concepts used in the management and treatment of cytomegalovirus infections in patients after hematopoietic stem cell transplantation.

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

Background. Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive tumors of the lymphatic system. Despite the frequency of occurrence, there is no single algorithm for treating DLBCL patients with poor prognostic factors. R-CHOP therapy does not allow achieving long-term complete remissions. Therefore, there is a need for second and subsequent lines of therapy. At the same time, the effectiveness of each subsequent therapy is low, while the toxicity increases. There are many randomized trials of the DLBCL treatment; however, there are only a few studies on the comparative efficacy of high-dose chemotherapy at the induction stage.The objective of the study: the evaluation of the effectiveness and toxicity of R-DA-EPOCH and R-mNHL-BFM-90 induction courses in DLBCL patients with poor prognostic factors in a randomized multicenter clinical trial “DLBCL-2015”.Materials and methods. As of April 2021, 140 patients from 13 medical institutions in Russia were included in the randomized multicenter clinical trial DLBCL-2015. As part of this study, the analysis of pharmacoeconomic factors and effectiveness of combined immunochemotherapy R-DA-EPOCH and R-mNHL-BFM-90 in patients with prognostically unfavorable DLBCL had been performed. From January 2018 to April 2021, this study included 41 patients (21 men, 20 women) with a newly diagnosed DLBCL, with 2 or more factors of an unfavorable prognosis, who were treated at the National Research Center for Hematology of the Ministry of Health of the Russian Federation. Of these, 21 patients received R-DA-EPOCH, and 20, R-mNHL-BFM-90 therapy. Median age for R-DA-EPOCH patients was 52 years (range 30–64); for R-mNHL-BFM-90 patients, 40 years (range 18–60). All patients had high-intermediate and high risk according to the international (IPI) and age-adjusted (aaIPI) prognostic index. The primary protocol endpoints were rates of complete remission, partial remission, disease progression, and hematologic and non-hematologic toxicity. Side effects were assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) criteria.Results. By the end of 6 induction courses, the frequency of achieving complete remission on R-mNHL-BFM-90 therapy was 100 % (20/20) compared to R-DA-EPOCH, where the complete remission rate was 71.4 % (15/21) (p = 0.0097), partial remission and progression were 14.3 % (n = 3) and 14.3 % (n = 3), respectively. Hematological toxicity on therapy according to the R-mNHL-BFM-90 scheme exceeded that on R-DA-EPOCH in terms of myelotoxic agranulocytosis (p = 0.0536), anemia (p = 0.0464) and thrombocytopenia grade III–IV (p = 0.0206). When assessing non-hematological toxicity at the compared courses, no statistically significant differences were noted, all complications occurred with the same frequency.Conclusion. Treatment according to the R-mNHL-BFM-90 protocol is highly effective as first line therapy in high-intermediate and high-risk DLBCL patients. The hematologic toxicity is higher on the R-mNHL-BFM-90 than on the R-DA-EPOCH therapy, but it is acceptable. Non-hematological toxicity in both programs is comparable.

Background. Splenic marginal zone lymphoma (SMZL) is an indolent non-Hodgkin’s B-cell lymphoma. It presents morphologically by mature lymphoid B-cells. They conform to these immunological characteristics of marginal zone lymphocytes from secondary follicles. The tumor B-cells of SMZL do not have specific markers of immunophenotype and requires the exclusion of other non-Hodgkin’s B-cell lymphomas. There is an annual increase in the incidence of SMZL. There are refractory forms and progressive course of the SMZL. There is a huge variety of the mechanisms of evading tumor cells from immunological control. Unlike solid tumors, B-lymphoproliferative diseases are characterized by the expression of HLA I/II and co-stimulatory molecules (CD80 and CD86). Therefore, tumor B-lymphocytes can act as antigen-presenting cells (APC) for T lymphocytes. The T-cell immune response is known to play an important role in antitumor control. It is known that effective activation of T-lymphocytes requires the formation of an immunological synapse and the presence of two activation signals (antigen recognition and co-stimulation of CD28-CD80/86). According to the modern concept of tumor development, there is a gradual selection of tumor clones. As a result, only tumor cells that are invisible to the immune system remain. Mechanisms of evasion of tumor B-cells of SMZL from immune surveillance are currently not fully understood and are being actively studied.Objective: to study the expression features of antigens involved in the formation of immunological synapse in patients with SMZL in peripheral blood.Materials and methods. The study includes 10 primary SMZL patients; all patients have stage IV according to the Ann Arbor classification. Splenectomy was performed for all patients as a first stage of treatment. Two patients had progression of SMZL after splenectomy, which required chemotherapy. The control group included 25 healthy donors. Peripheral blood was used as a material for analysis. The study was conducted on a 6-color BD FACS Canto II flow cytometer (BD Biosciences, USA) immediately after diagnosis.Results. Tumor B-cells of SMZL are different from B-cells of healthy donors with a greater proportion of CD80+, FAS+, PD-1+-cells, which may correspond to activated B-cells. The proportion of CD4+PD-1+ and CD8+PD-1+ T-cells in patients with SMZL was higher in comparison with the control group. There was a large proportion of T-cells expressing PD-1 in the group of patients with SMZL progression after splenectomy in comparison with the group of patients with indolent course of SMZL. Conclusion. Thereby, tumor B-cells of the SMZL retains the features of non-tumor analogues. The most significant mechanism for evading immune surveillance in an SMZL is inhibition of the T-cell immunity via the PD-1–PD-L1 pathway. The most pronounced inhibition of T-cell immunity causes an uncontrolled tumor process.

Background. In addition to anti-HLA-I and anti-HPA-antibodies and specific cytotoxic T-lymphocytes, another cause of immune refractoriness to donor's platelet transfusions could be a platelet-associated different classes immunoglobulins PAIg (G, M, A) and C3 / C4‑components of complement system (PAC3, PAC4). These markers can be detected by flow cytofluorometry of double-stained platelets. The fixation density of immunoglobulins and components of complement systems were measured by the mean fluorescence intensity (MFI).Objective: to study additional factors that aggravate the course of refractoriness to donor's platelet transfusions in patients with aplastic anemia (AA) and hemoblastosis.Materials and methods. 77 patients (AA – 47, myelodysplastic syndrome (MDS) – 10, acute myeloid leukemia (AML) – 20) admitted to National Research Centre for Hematology during 11.09.2016–04.28.2018 were enrolled in the study. M / f ratio was 33 / 44, median age was 36 yrs. (19–71 yrs.). Plasmapheresis and cross-matching for PRP selection were used for patients with refractoriness to donor's platelet transfusion. PAIg (G, M, A) and PAC3 / C4 detection and density (MFI) were evaluated in all patients by flow cytofluorometry of doublestained platelets (CD41a-PE; IgA, M, G-FITC; C3 / C4‑FITC) and MFI measurement. Patients with AA were investigated on different stages of therapy and if refractoriness to donor's platelet transfusion is developed. Blood donors (n = 28) MFI measurement results were established as negative control.Results. It was found that MFI PAIgG/M/А and PAC3/С4 was higher in all groups of the patients (АА, MDS, AML), as compared with donors. MFI of PAIgM and PAIgA in patients were significant higher than MFI of PAIgG and PAC3 / C4. Combination of PAIgM / A, PAIgM / C3 / C4 and PAIgA / C3 / C4 were more frequent. Multiple transfusions of PRP were associated with PAIgA and PAC3 detection. Development of refractoriness to donor's platelet transfusions was accompanied by alloantibodies (HLA-I, HPA) and PAIgM, PAC4 detection. In patients of AA group during development of refractoriness to donor's platelet transfusions and multiple infection complications the high density of PAIgM and PAIgA were identified. Relapse of AA was accompanied MFI of PAC3 density increment.Conclusion. In addition to application of a certain transfusion therapy algorithm it is also necessary to detect PAIg (G, M, A) and PAC3 / C4 for prediction of severe refractoriness to donor's platelet transfusions.

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.

Background . The study of influence of residual tumor mass, determined by magnetic resonance imaging (MRI), on the progression-free survival (PFS) remains an actual problem. Since the visual assessment of tumor bone marrow lesion can be one of the criteria for the subsequent personalized treatment choice in multiple myeloma patients.The objective of study was to determine the effect of bone marrow lesions detected by MRI after autologous hematopoietic stem cells transplantation (auto-HSCT) on PFS in multiple myeloma patients.Materials and methods . The prospective study included 60 patients who underwent spine and pelvic bones MRI on the 100 th day after autoHSCT.Results . Focal bone marrow changes were found in 47 of them – from 1 to 56 lesions (mean 6 ± 9). Significant (p = 0.01) differences of PFS in multiple myeloma patients depending on the presence or absence of tumor mass on 100 th day after auto-HSCT were revealed: with MRI negative status, 2-year PFS was 89 % versus 50 % in a group of patients with residual tumor mass.Conclusion . MRI-negative status after auto-HSCT is a favorable prognostic factor contributing to prolonged disease-free survival.

Background. Follicular lymphoma (FL) is the most common type of indolent lymphomas and accounts for 20–30 % of all non-Hodgkin’s lymphomas detected. High risk of recurrence and elderly patients make it difficult to choose induction therapy for FL. The R–B course in comparison with the R–CHOP course increases the progressive free survival (PFS) of FL patients and is less toxic. International studies have not studied the efficacy and toxicity of the R–B course due to various cytological types of FL.Aim of the study – assessment of the effectiveness and toxicity of the R–B course (with R support) in general and depending on the different cytological types of FL, the assessment of overall survival (OS) and PFS (adverse events: progression, relapse, death); identification of risk factors for an adverse event in general and death, in particular. The main endpoint of this study is selected BPV.Materials and methods. We performed a prospective, multicenter, open-label trial in Russia since June 1, 2013 till June 1, 2018. The study included 74 patients with FL. Median age of patients was 59 years (from 30 to 78 years). Treatment was completed in 66 patients, so this group of patients was analyzed. Ratio between men and women was 1:2. 32/66 of patients (48 %) were older than 60 years old. Patients received rituximab 375 mg/m2 on day 1 and bendamustine 90 mg/m2 on days 1 and 2 of a 4-week cycle (6 cycles). 49/66 (74 %) of patients were diagnosed with FL grade 1, 10/66 (15 %) – grade 2, 7/66 (11 %) – grade 3A. 34/66 (52 %) patients had nodular tumor growth type, 28/66 (42 %) – nodular-diffuse, 4/66 (6 %) – diffuse. High risk according to FLIPI had 25/59 (42 %) of patients with cytologic grade of FL 1–2 and 7/7 (100 %) of patients with FL grade 3A. Extranodal lesions were revealed in 26/66 (39 %) of cases: in 4/66 of cases – orbit, in 2/66 – parotid gland, in 5/66 – lungs, in 4/66 – intestines, in 2/66 – stomach, 2/66 – pancreas, 2/66 – uterus, 2/66 – skin, 1/66 – subcutaneous tissue, 3/66 – vertebrae, in 1/66 – latticed maze and nasal passages, 1/66 – kidneys, 1/66 – root of the tongue. In 23/26 (88 %) of cases extranodal lesion was revealed in generalized stage of FL (including lymph nodes and bone marrow). Extranodal lesions were found in 37 % of patients with FL grade 1–2, and 57 % with FL grade 3A. Bulky also was observed more frequently in pts with FL grade 3 3/7 (43 %) than in patients with FL grade 1–2 20/59 (34 %). (The risk factors of an adverse event are also its predictors in this study.)Results. Complete remission of disease was achieved in 40/66 (61 %) patients, partial remission – 13/66 (19 %) patients. Tumor progression observed in 11/66 (17 %) cases, patients were withdrawn from the protocol. А partial tumor response was achieved in 2/66 cases (3 %) and patients received high-dose therapy after 4 courses of R–B. Five-year (as well as the 3-year) overall survival (OS) of all patients (n = 66) in R–B was 90 % (95 % confidence interval (CI) 78–96), 5-year PFS – 70 % (95 % CI 55–85) and a 3-year PFS – 75 % (95 % CI 60–89). The cumulative incidence of relapse (considering competing risks of progression and death) at the 3th year after initiation of treatment was 11 % (95 % CI 3–19). The following independent statistically significant (p ≤0.05) predictors of PFS (measured in the onset of the disease) were determined (as a result of a stepwise multivariate cox regression analysis): 1) cytological type of tumor (only type 3A is significant); 2) involvement of nodal zones (more than 4); 3) presence of a conglomerate of tumor lymph nodes larger than 6 cm (bulky); 4) Ki-67 protein expression (more than 35 %). The first 3 characteristics (as well as the sign «presence of extranodal foci», close to the level of significance) are independent statistically significant predictors of OS. In the single factor analysis the following characteristics (besides the above) were significant: index FLIPI (significant only 5 points against all others), bone marrow damage, β2-microglobulin (more than 2.2 mg/L), age (over 68 years) and hemoglobin (less than 110 g/dL).Conclusion 1. The independent negative predictors of OS and PFS in follicular lymphoma were determined. 2. Of the predictors of an adverse event identified, the greatest risk (as a result of a multivariate analysis) is associated with a 3A cytological type of tumor. 3. The FLIPI index has a predictive value not only for the determination of OS, but also for the PFS (moreover, in reduced dichotomous form: 5 points against all the others combined). 4. An increase in the time interval between the first manifestations of follicular lymphoma (lymph node enlargement / appearance of a tumor formation) and the start of therapy beyond a certain threshold value (estimated to be approximately 22 months) is associated (according to the results of univariate analysis) with an increased risk of an adverse event. One of the reasons for the increase in this time interval is associated with expectant medical tactics adopted during the slow development of the clinical picture of the disease. The obtained result shows that the low rate of development of the clinical picture of the disease does not correlate with the low risk of adverse events, and, therefore, cannot be a determining factor when deciding whether to start treatment. 5. The morphology of the tumor is the determining factor in the choice of induction therapy. 6. After achieving full/partial remission of FL, there is a constant risk of recurrence of the disease (by the age of 3 from the termination of treatment, the risk is 11 % (95 % CI 3–19)). 7. The R–B course effectively sanitizes the bone marrow. 8. The R–B allows performing stem cells mobilization and autoSCT that is actual in FL patients with bone marrow involvement. 9. The treatment regimen of R–B is effective and has a relatively low toxicity, so it is advisable in the treatment of elderly patients.

The aim of the study was to evaluate the profile and risk factors for acquisition of infections in patients with de novo multiple myeloma (MM) on the 1st chemotherapy cycle (CC).Materials and methods. Study included patients with de novo MM undergoing chemotherapy from January 2013 till November 2017 in National Research Center for Hematology, Russia.Results. A total of 156 patients with de novo MM (median age 61 years) were included in the study. Follow-up period was 21–82 days (median 26 days), first CC contained bоrtezomib. Infections occurred in 77 (49.4 %) of patients with MM, from them 29 (37.7 %) – on admission, 48 (62.3 %) – throughout treatment. Solitary infections were in 47 (61%) of patients, multiple infections – in 30 (39 %) of patients. The most prevalent type of infection was pneumonia (62.3 %), followed by urinary tract infections (27.3 %) and herpesvirus infections (24.7 %). 30% of patients with infections were afebrile. Significant risk factors associated with infections at admission and during CC were ECOG score 4, anemia, hypercalcemia, humoral immunodeficiency, admission from other hospital, use of antibiotics prior to first CC. Additional risk factors for infections at admission were Durie–Salmon stage III MM, paresis, lower extremity paraplegia and dysfunction of the pelvic organs, whereas during treatment – ISS stage III MM and renal failure. Infections were uncommon in patients with ISS stage I MM (7.8 %). Mortality after 1st CC was 1.9 % caused by pneumonia and acute respiratory failure.Conclusions. Patients with de novo MM undergoing 1st CC had high incidence of infections with a prevalence of pneumonia. Factors associated with infections were stage III MM, serious illness, admission from other hospital, humoral immunodeficiency, and renal failure.

Introduction. Patients with hematological malignancies undergoing chemotherapy (CT) have high incidence of infections which profile is affected by various factors including neutropenia.Objective was to evaluate incidence and type of infections in patients with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) according to neutropenia duration.Materials and methods. Prospective study (2013–2015) included 110 patients (66 AML, 44 ALL) that received 480 CT cycles throughout 6 month.Results. Neutropenia with median duration of 15 (2–55) days was in 288 (60 %) of CT cycles. Infections occurred in 242 (50 %) of CT cycles and predominated in neutropenic compared to non-neutropenic patients (80 % vs 6 %, p

Objective. To study the histological structure of bone marrow (BM) and plasmacytoma tumor substrate in patients with multiple myeloma (MM). Materials and methods. The study included 35 patients (19 men and 16 women) aged 23 to 73 years with newly diagnosed MM. At the first onset of the disease plasmacytoma was diagnosed in 21 patients: bone plasmacytoma, associated with skeletal bones – in 14 patients; extramedullary plasmacytoma, emerging in various organs not connected with bone tissue – in 7 patients. All patients underwent BM trephine biopsy and plasmacytoma biopsy with subsequent histological examination. BM and plasmacytoma histological specimens were studied using LEICA DM4000B microscope. Frequency domain analysis (cross tables, Fisher–Freeman test) was used for data statistical analysis.Results. The analysis showed that the histological features of BM in MM patients with extramedullary plasmacytoma statistically significantly differed from that in MM patients with bone plasmacytoma and without plasmacytoma. As a result of the analysis, the relationship between BM morphological variant and tumor advancement became apparent. When comparing the morphological pattern of the bone and extramedullary plasmacytomas, no significant differences were found, however, the substrate of the extramedullary plasmacytoma was more often represented by tumor cells with immature morphology as compared to the substrate of the bone plasmacytoma.Conclusion. The established differences in the histological structure of the BM in MM patients with extramedullary plasmacytoma suggest that this type of the disease stands apart and requires further detailed pathomorphological study.

Background. Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that manifests by the accumulation of tumor monoclonal B-lymphocytes in the bone marrow, peripheral blood and secondary lymphoid organs. Recently it was found that CLL cells are able to form immunological synapses with microenvironment cells, directly and indirectly affecting their function. Therefore, it became clear that the pathogenesis of CLL is not only escape of apoptosis but also the ability of CLL cells to cause T-lymphocyte anergy, thereby avoiding immune surveillance.Objective: to study the expression of FAS, co-stimulatory molecules CD80 and CD86, PD-1, PD-L1 on CLL cells, and also to study the basic subpopulations of T-cells (naїve, memory, effector cells).Materials and methods. The study included 46 CLL patients: 16 patients with disease progression after chemotherapy and 30 patients with newly diagnosed CLL. “Primary” patients are categorized according to J. Binet’s CLL stages. Stage A was established in 14 patients, B – 10, C – 6. The control group included 29 healthy donors. Peripheral blood was used as a material for analysis. The study was performed on a 6-color flow cytometer BD FACS Canto II (BD Biosciences, USA).Results. In CLL patients, the proportion of CD80+, CD86+, FAS+ B-cells was significantly lower than in donors. In “primary” patients the proportion of CD80 + CLL cells was higher than in patients with CLL progression. Among “primary” patients the proportion of CD80+ and CD86+ was lower in advanced stages of the disease. In patients with CLL progression the proportion of FAS+ B cells was higher than in “primary” patients. The proportion of PD-1+ B cells in CLL patients was higher than in donors and “primary” patients. The proportion of PD-1+ tumor cells was significantly lower in advanced stages of the disease. The proportion of PD-L1+ B cells in CLL patients was lower than in donors. Among the “primary” patients, the proportion of PD-L1+ B-lymphocytes was higher in stage A. The proportion of PD-1+ Thelpers was higher in CLL patients than in donors, and among “primary” patients it was higher in advanced stages of the disease. The proportion of PDL1+ T-helpers and cytotoxic T-cells in CLL patients was lower than in donors. The proportion of naїve cells (CD95-CD28+) in patients compared with donors was lower and the proportion of effector cells (CD95+ CD28–), memory cells (CD95 + CD28 +) was higher, a proportion of CD8+ memory T-cells was higher among patients in the advanced stage of CLL.Conclusion. Therefore, a decline the CD80/CD86+ B-cells in CLL can cause ineffectiveness of an immunological synapse between tumor cells and T-cells, which leads to anergy of T-lymphocytes. Decline expression of the FAS receptor allows tumor CLL cells to avoid FAS-mediated apoptosis. A change in the T-cell pool toward memory cells and effectors, the acquisition of a CD4+PD-1+ (“exhausted”) phenotype impaired antitumor immunity and possible leads to disease progression.

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.