Introduction. The question of the most adequate treatment strategy of AML in cases when it is impossible to perform allogeneic HSCT because of any reason still remains open.

The aim of this study was to assess the long-term survival of patients with AML who received chemotherapy (CT) or autologous HSCT as consolidation in the first remission of the disease. It was included 135 patients aged 18 to 67 years, with a verified diagnosis of AML (except FAB M3) in the study. Of these, 100 patients received only CT, 35 patients received consolidation with autologous bone marrow transplantation. Patients who achieved remission after completion of induction CT courses received one of three treatment options as consolidation: 1) chemotherapy of standard-intensity (sCT), 2) high-dose chemotherapy (HDCT), 3) autologous HSCT (autoHSCT) conducted after 1–2 courses of high-dose CT. Adverse prognostic factors were identified as: age over 40 years, hyperleucocytosis more than 50,0 × 10 9/L and unfavorable cytogenetic and molecular-biological risk group.

Materials and methods. Depending on the number of prognostic factors at the onset of disease relapse-free survival (RFS) was 47 % in their absence, 45 % in the presence of 1 factor, in the presence of 2 factors – 14 % (p = 0,000), regardless of the variant of consolidation therapy (sCT, HDCT, autoHSCT). A high level of white blood cells adversely affects OS (38 % vs. 22 %) and increases the frequency of relapse (52 % vs. 69 %) when performing only CT (sCT and HDCT). At initial white blood cells level more than 50,0 × 10 9/L the 5-year OS was 60 % when performing both autoHSCT and HDCT. Performance of autoHSCT at failure to achieve remission after the 1st induction course CT is associated with the best 2-year OS (62 % vs. 35 %, p = 0,05), EFS (50 % vs. 22 %, p = 0,05) and RFS (50 % vs. 37 %, p = 0,05) in comparison with HDCT and sCT. In favorable cytogenetic risk group 5-year RFS was 80 % when performing autoHSCT and 67 % when performing HDCT; the 5-year OS was 80 % regardless of consolidation therapy option.

Conclusion. AutoHSCT is the preferred consolidation option in favorable risk group patients, and after failure to achieve remission after the 1st CT course.

Background. Extramediastinal and bone marrow involvement in PMBCL patients in the onset of the disease is an exception to the rules and complete information, except for the word “rare”, in Russian and international literature is not available.

Objective: to characterize PMBCL patients with extramediastinal involvement.

Materials and methods. From 2007 to 2017 diagnosis of PMBCL was established in 157 patients according to WHO criteria with extramediastinal involvement in 16 (10.2 %) patients, 3 of them were at different stages of pregnancy. The median age was 27 years (23–69). Patients received different therapy protocols: m-NHL-BFM-90, R-DA-EPOCH и VACOP-B.

Results. One extramediastinal lesion was verified in 11/16 (68.7 %) patients, multiple – in 5/11 (31.3 %). The most common localizations were: pancreas – 6 (37.5 %), kidneys – 5 (31.2 %), ovaries – 3 (18.7 %), liver – 3 (18.7 %), bone marrow – 3 (18.7 %) and breast – 2 (12 %) cases. Involvement of stomach, bones, soft tissues, spleen, pelvis, adrenal gland was revealed in one case each. In 15/16 cases, extramediastinal lesions were combined with antero-superior mediastinum involvement and only in 1 cases an isolated lesion of the soft thorax tissues without involvement of mediastinal structures was revealed. Five-year overall survival in the group of patients with classical PMBCL who received R-DA-EPOCH, m-NHL-BFM-90 and cohort of patients with extramediastinal lesions was comparable and was 93 %. As a result of the analysis, in 10.2 % (16/157) of cases extramediastinal involvement was revealed. In all cases, there is involvement of organs and tissues, but not the lymph nodes. In 18.7 % (3/16) of cases there was bone marrow involvement, confirmed by molecular and histological studies.

Conclusion. Involvement of the antero-superior mediastinum and the presence of extramediastinal lesion, bone marrow involvement is not excluding criterion for PMBCL, but requires differential diagnosis with DBCL, including standard and molecular methods. Is isolated extramediastinal involvement in PMBCL a poor prognostic factor, is uncertain because of the small number of observations.

Background. Even 100 years after the first attempts to introduce the chemotherapeutic approaches (in 1918) and despite the completely formed notions of myeloproliferative diseases as a group of malignant neoplasms, in the majority of patients with Ph-negative myeloproliferative neoplasms (MPN), a symptomatic, in fact, therapy approach – the impact on peripheral blood indices and nonspecific thromboprophylaxis – is allowed. The limitations of classical cytoreduction and current targeted therapy, as well as the conviction of most specialists in the impossibility of adequately containment of disease progression, continue to be the main factors that keep physicians from the early start of pathogenetic therapy.

Objective: to study the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b) in early (non-risk-adjusted) therapy of classical Ph-negative myeloproliferative neoplasms in initial use and after therapy with other pegylated interferons (PEG-IFN).

Materials and methods. Twenty seven patients with polycythemia vera or essential thrombocythemia, without considering risk, received cePEG-IFN alpha-2b: initially, or after 6 or 12 months of other pegylated interferon therapy, in a dosage of 200 μg per week, with a decrease to 100 μg per week if 2 degree hematological toxicity developed. Hematological and molecular responses were assessed. Follow-up – from 20 to 46 months.

Results. In all groups, a hematologic response comparable in depth and dynamics, as well as a molecular response as a steady decrease in the JAK2V617F allelic load, was achieved. There was no effect on the results of change to therapy with cePEG-IFN alpha-2b. CePEGIFN alpha-2b showed less dose-limiting toxicity for neutropenia and better pharmacoeconomic feasibility.

Discussion. New data about mechanisms of antiproliferative effects of interferon alfa preparations are given. The pharmacological advantages of cePEG-IFN alpha-2b are discussed: superiority in pharmacokinetic parameters, the presence of one position isomer purity of the drug substance, the convenience of self-application.

The review contains data on new important aspects of the pathogenesis and treatment of anemia of chronic diseases. The complex multicomponent genesis of this anemia is shown, which is based on the disturbances in iron metabolism, damage of proliferation and differentiation of erythropoiesis cells, a decrease in the synthesis and biological activity of erythropoietin. The value of blood transfusions, iron preparations and erythropoiesis-stimulating agents in the treatment of patients with anemia of chronic diseases is shown. It is established that the safety data of these methods are quite contradictory, further studies are needed in this direction with the aim of developing uniform principles for the diagnosis and treatment of this anemia. Comparative analysis results of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α) concentration in patients with malignant neoplasms with anemia and without it are presented, as well as correlation analysis for evaluation their influence on the number of erythrocytes and hemoglobin concentration. Sixty three patients with stage II–IV disease were examined. In patients with anemia, compared with the control group, higher levels of IL-6 (41.5 (3.8–31.1) and 7.1 (0.00–9.40) pg/ml), TNF-α (58.6 (36.1–81.1) and 8.25 (1.3–13.6) pg/ml) and IL-10 (18.3 (4.5–14.4) and 0.9 (0.3–5.5) pg/ml) were revealed (p <0.05). For IL-6, there was a correlation with erythrocytes (r = –0.55), hemoglobin (r = –0.52); for TNF-α, a correlation with erythrocytes (r = –0.74), hemoglobin (r = –0.69) was revealed; for IL-10, there was a correlation with hemoglobin (r = –0.74) and erythrocytes (r = –0.6). The results confirm the importance of these cytokines in the genesis of anemia in cancer patients.

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.

Myelodysplastic syndromes (MDS) are heterogeneous group of clonal hematological neoplasms characterized by cytopenias, sighs of dysplasia and high risk of transformation in acute myeloid leukemia. Diagnostics of MDS requires a comprehensive approach, but even when performing cytological, cytogenetic, molecular and histological studies, it is not always possible to establish a diagnosis. Multicolor flow cytometry (MFC) is a high-tech method, increasingly used in the diagnosis of various hematologic diseases. Over the last years, MFC is standardized for assessing of dysplasia in all cell compartments of the bone marrow. Many research groups have demonstrated high sensitivity and specificity of this diagnostic approach, which indicates the necessity of integration of flow cytometric study into diagnostic protocols of MDS.

Background. Flow cytometry is one of the key technologies for acute lymphoblastic leukemia (ALL) diagnostics. Nevertheless lack of technological standards hampers implementation of immunophenotyping data in treatment protocols.

Objective: development of harmonized guidelines for flow cytometric diagnostics of childhood ALL.

 Materials and methods. Three reference laboratories of the immunophenotyping group “Moscow–Berlin” took part in the development and standardization of approaches to the cytometric determination of the minimal residual disease. The sequence of steps for staining with monoclonal antibodies, selection of reagents for immunophenotyping, flow cytometer adjustment algorithms were discussed.

Results. We developed and implemented in multicenter setting the harmonized approach for immunophenotyping flow cytometric childhood ALL. Successful integration of this protocol in the multicenter group has shown good level of our approach reproducibility.

 Conclusion. These results will allow implementing diagnostic standards in stratification system of pediatric ALL treatment protocols of russianbelarusian multicenter group.

Patients with acute myeloid leukemia (AML) have a high risk of relapse. Determination of the presence of residual tumor cells during the remission of AML allows predicting the onset of relapse. Slow decrease of blast cells after induction courses is associated with a high probability of relapse. There are two most sensitive methods for determining minimal residual disease (MRD): molecular (polymerase chain reaction – PCR, droplet digital PCR, next generation sequencing – NGS) and immunophenotypic (multicolor flow cytometry – MFC). Both methods have advantages and disadvantages. The molecular diagnostic method is more sensitive, but it takes more time to get the result (from several days). Measurement of MRD by PCR is applicable in 40–50 % of AML patients, and by MFC – in 90 % of patients. The MFC method is based on the identification of antigens combination that is characteristic of tumor cells and is not found on normal hematopoietic cells. There are several drawbacks of the MFC method: the change of tumor clone immunophenotype during treatment, the inadequate difference in the antigen profiles of tumor cells and normal cells, difficulties in evaluating the MRD status in low cellularity bone marrow or blood sample. In AML patients the effect of MRD, measured by the MFC method, on long-term treatment outcomes was well-demonstrated. Evaluation of early MRD status shows tumor chemosensitivity and therapy efficacy. Despite the different approaches in MRD detection, thresholds and the combination of monoclonal antibodies, the lack of standardization, “positive” MRD values in early or later stages of therapy worsen the disease-free (DFS) and overall survival (OS) in AML patients. So far, the principles of MRD-directed therapy have not been developed, but protocols exist with the use of targeted drugs in combination with standard chemotherapy that help to reduce the MRD level. It is proved that the intensification of treatment does not affect the quantitative value of MRD and the long-term results of therapy. New prospective studies are needed to search for universal MRD markers, to create a standardized panel of monoclonal antibodies and to develop a specific therapy strategy in accordance with the MRD values.

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.