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The purpose of this article is to identify the main trends in the influence of digital inclusion on the process of political socialization of high school students. Unconventional political activity of schoolchildren in recent years has increased the interest of scientists in the study of political socialization of children and adolescents, as well as factors influencing this process and its results. The empirical base was made up of the materials of the author's research of high school students in Krasnodar (questionnaire survey and expert sessions), as well as materials of sociological research by other authors. The level of involvement in the political life of citizens and the constructive experience of civil and political practices in a digital society largely depends on the updated set of digital competencies of citizens. Digital inclusion has the maximum impact on the political socialization of Generation Z, whose primary socialization occurred in the digital era. The level of involvement of Krasnodar high school students in digital communication is estimated as medium and high, and the level of digital competencies as medium and low. The authors have identified such vectors of the influence of digital inclusion on the political socialization of schoolchildren as: the movement from the sequence of "five transitions" of youth to their overlap and related problems of managing multitasking of identity construction; the change in the configuration of agents of political socialization from hierarchical to hybrid and the emergence of groups of youth outside the influence of traditional agents of socialization; the increasing role of digital media personalities in the formation of political views of adolescents; the development of digital technologies for the formation of political and civic identity.

Over the past decade NGS has expanded our understanding of the genomic landscape of hematological malignancies. New biomarkers discovered during NGS are now widely used in clinical practice to improve diagnosis, stratify patients into prognostic groups, and select targeted therapy for Ph-MPN patients.To assess possibilities of NGS in diagnosis and determination of prognostic features of disease course in Ph-MPN patients.The study included 36 patients from clinics in Moscow and St. Petersburg (17 men and 19 women), the median age was 55 (IQR 27-79) with diagnosed PV, ET, PMF, MDS, AML.A panel of 116 genes with an average reading depth of 200x or 1000x on MiSeq (Illumina) was used. NGS panel had a detection limit of 3% variant allele frequency. The clinical significance of mutations was determined using COSMIC and ClinVar.Genetic abnormalities were detected in all patients. On average, 10 mutations per one patient were revealed, including 4 somatic mutations in 92% (33/36) patients. In 70% (25/36), from 1 to 3 mutations with known clinical significance were found. In all patients without driver and somatic mutations (ASXL1, EZH2, etc.) and chromosomal aberrations, somatic mutations (both clinically significant and unknown clinical significance) were detected, that served as clonality confirmation. All patients were divided into two groups: 1) driver mutations, normal karyotype (16/36) (favorable prognosis) and 2) triple-negative mutational status (20/36) with additional patients having mutations in epigenetic regulators genes (4/36) (unfavorable prognosis). In the first group, NGS revealed additional mutations in 8/16 (50%) patients (ASXL1, EZH2, IDH1) and in 3/16 (19%) were noted mutations in TET2 gene. In an unfavorable group, additional mutations were also found in genes of epigenetic regulation (ASXL1, IDH1, SRSF2) and in signal transduction genes (RAS genes, PTPN11) and TET2.NGS data can confirm disease clonal nature, assess disease prognosis, and select target therapy for patients with Ph-negative myeloproliferative neoplasms. To get new information it is possible to expand the panel of sequenced genes, as well as study other genetic mechanisms underlying disease pathogenesis (e.g., changes in gene expression level, microRNAs, or transcription factors).

Allogeneic hematopoietic stem-cell transplantation (HSCT) remains the only curative option for patients with advanced chronic myeloid leukemia (CML). However, outcome is dismal and of short follow-up. The objective of the study was to determine long-term outcome and risk factors in patients with a history of CML Blast Crisis (BC; n = 96) or accelerated phase (n = 51) transplanted between 1990 and 2018. At transplant, patients had a median age of 39 (range 7–76) years and were in ≥CP2 (n = 70), in AP (n = 40) or in BC (n = 37) with a diagnosis-HSCT interval of median 1.9 (range 0.3–24.4) years. Overall survival (OS) amounted 34% (95% CI 22–46) and progression-free survival (PFS) 26% (95% CI 16-36) at 15 years. Adverse risk factors for OS and PFS were low CD34+ count in the graft, donor age (>36 years) and BC. Cumulative incidence of Non-Relapse Mortality (NRM) was 28% (95% CI 18–38) and of relapse (RI) 43% (95% CI 33–53) at 15 years. PB-HSCT and HSCT after 2008 were favorable prognostic factors for NRM, while family donor and patient age >39 years were independently associated with higher RI. HSCT resulted in long-term OS in patients with advanced CML. OS was improved in non-BC patients, with donors ≤36 years and with higher CD34+ dose in the graft.

Background. Mastocytosis is a disease caused by proliferation and accumulation of clonal mast cells in one or more organs. It is often associated with other hematological tumors. Aggressive forms of mastocytosis (AFM) require specific therapy. In non-aggressive forms of mastocytosis (NFM) symptomatic treatment is needed. Aim. To analyze the clinical course and treatment outcomes in different forms of adult mastocytosis. Materials & Methods. The retrospective analysis was based on the records of patients who received in-person and distance consultation within the period from 11/2008 to 11/2020. The analysis of complaints in disease onset and over time was carried out using questionnaires. NFM patients received symptomatic treatment with antihistamines. To all AFM patients chemotherapy was administered. Results. The analysis includes the data of 58 patients: 39 (67.2 %) women and 18 (32.8 %) men. The median age was 40 years (range 18-79 years), the median age on diagnosis was 39 years (range 1-79 years). In all patients skin rashes were reported. The median age of the first skin manifestations was 25 years (range 0.1-70 years). In-person monitoring was conducted in 34 (58.6 %) patients, 24 (41.4 %) patients received distance consultations. Median follow-up was 56.5 months (range 3-564 months). In 8 (13.7 %) patients mastocytosis was diagnosed in childhood with the median of 9 years (range 0-15 years). The diagnosis was morphologically confirmed in 46 (79.3 %) patients. Main complaints included pruritus (67.2 %), edema and erythema response to various irritants (62 %). In 45 (77.5 %) patients NFMs were reported. The regular symptomatic treatment of 78.8 % of NFM patients consisted only of antihistamines (57.9 %), and 2 (4.4 %) patients noted poor disease symptom control. One (2.2 %) patient died of associated chronic myelomonocytic leukemia. None of NFM patients required cytoreductive treatment. AFMs were diagnosed in 13 (22.4 %) patients, 5 (38.4 %) out of them had mast cell leukemia. The indications for starting chemotherapy were cytopenia (n = 3; 23 %), extensive osteolysis (n = 7; 53.8 %), ascitic syndrome with portal hypertension (n = 6; 46.1 %). Overall survival of AFM patients was 84.6 % (n = 11) with median follow-up of 80 months (range 12-131 months). Conclusion. NFM prognosis is favorable. Antihistamines are effective in relieving complaints of most patients. Cytostatic treatment of AFM in some patients provides long-lasting antitumor response.

The present review provides the analysis of theoretical background and therapy of prognostically poorest EV/1-positive myeloid leukemias and myelodysplastic syndromes which is performed at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. The focus is on the evidence of the dominating role of EV/1 gene in impaired epigenetic regulation of hematopoiesis and, thus, on the feasibility of allogeneic hematopoietic stem cell transplantation with hypomethylating agents and/ or trans-retinoic acid used for these diseases treatment.

Ph-negative myeloproliferative neoplasms (MPN) are rare oncohematological diseases characterized by long duration and indolence. World epidemiological data on these diseases considerably vary depending on geographical area and time frame of the study. The breakthrough in the understanding of MPN pathogenesis, observed in the early 2000s, enabled to elaborate approaches to differential diagnosis and treatment of Ph-negative MPNs as well as to improve their prognosis. Although these approaches are specified in the Russian clinical guidelines, physicians still face challenges in their implementation in practice. The present review provides a detailed description and analysis of literature data on epidemiology, pathogenesis, and principles of Ph-negative MPN diagnosis and treatment. It also describes the situation in Saint Petersburg as an example of existing challenges in management of patients with Ph-negative MPNs in Russia and offers potential solutions.

Classical Ph-negative myeloproliferative neoplasms (MPN) constitute a group of diseases including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Over the past decade, the approaches to understanding of MPN pathogenesis and therapy have considerably changed. At the same time, etiological factors and pathophysiological mechanisms of disease progress are being thoroughly studied. The improvement of diagnosis methods and new approaches to therapy can reduce complications and mortality risks. The review outlines the current diagnosis methods, such as the molecular genetic one, and provides prognostic scores. Different methods of conservative therapy are assessed. Special attention is paid to quality of life measurement and targeted treatment of patients.

The development of National clinical guidelines on diagnosis and treatment of Ph-negative myeloproliferative neoplasms comes in response to the need to standardize the approach to diagnosis and treatment. The availability of clinical guidelines can facilitate the choice of adequate treatment strategy, provides practicing physicians with exhaustive and up-to-date information on advantages and shortcomings of different treatment methods as well as lets health professionals better assess expected extents of treatment required by patients. In 2013 a working group was formed to develop and formulate clinical guidelines on the treatment of myeloproliferative neoplasms. These guidelines were first published in 2014, afterwards they were revised and republished. The dynamic development of current hematology presupposes constant updating of knowledge and implementation of new diagnosis and treatment methods in clinical practice. In this context clinical guidelines present a dynamic document to be continuously amended, expanded, and updated in accordance with scientific findings and new requirements of specialists who deal directly with this category of patients. The present edition is an upgraded version of clinical guidelines with updated information on the unification of constitutional symptoms assessment using MPN-SAF TSS questionnaire (MPN10), on applying prognostic scales in primary myelofibrosis, assessing therapy efficacy in myeloproliferative neoplasms, revising indications for prescription, on dose correction, and discontinuation of targeted drugs (ruxolitinib). The guidelines are intended for oncologists, hematologists, healthcare executives, and medical students.

Aim. To comparatively analyze myelofibrosis treatment outcomes with the use of ruxolitinib versus ruxolitinib with subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) as well as to assess the efficacy of ruxolitinib in pre- and post-transplantation periods. Materials & Methods. The study enrolled 78 myelofibrosis patients who were referred to the RM Gorbacheva Scientific Research Institute to determine the indications for allo-HSCT. Allo-HSCT was performed in 33 patients, among them 32 patients with ruxolitinib pre-conditioning (ruxolitinib + allo-HSCT group). They received reduced intensity conditioning (fludarabine 180 mg/m2 and busulfan 10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included cyclophosphamide 50 mg/kg on Day +3 and Day +4, ruxolitinib 10 mg per day from Day +5 to Day +100 (n = 31), rabbit antithymocyte globulin, tacrolimus, and mycophenolate mofetil (n = 2). Ruxolitinib without allo-HSCT was administered to 45 patients (ruxolitinib group). Between the groups there were no significant differences with respect to gender, age, diagnosis, and molecular genetic variant. Results. Median therapy duration in ruxolitinib group was 16 months (range 2-78 months). In 2 (4 %) patients partial response was achieved, 8 (20 %) patients showed clinical improvement, in 16 (39 %) patients stable disease (SD) was reported, in 15 (37 %) patients disease progression (DP) was detected. The treatment succeeded in reducing the spleen size in 8 (20 %) patients and in relieving disease symptoms in 16 (39 %) patients. Cumulative incidence of progression within 3 years was 44 % (95% confidence interval [95% CI] 27-60 %). In ruxolitinib + allo-HSCT group median ruxolitinib therapy duration was 7 months (range 3-22 months). As a result, clinical improvement in 9 (28 %) cases, SD in 17 cases (53 %), and DP in 6 (19 %) cases were observed. In 5 (20 %) patients acute GVHD of grade 2-4, in 3 (12 %) patients acute GVHD of grade 3-4, and in 6 (24 %) patients chronic medium severity GVHD were identified. Within 1 year nonrelapse mortality was 28 % (95% CI 14-44 %). The 3-year cumulative incidence of relapse was 12 % (95% CI 3-28 %) in ruxolitinib + allo-HSCT group. According to the landmark analysis performed throughout 6 months from the first visit to the center, the 3-year overall survival in the group with allo-HSCT was 80 %, whereas in ruxolitinib group it was 41 % (p = 0.022), 12-month landmark analysis resulted in 77 % and 43 % (p = 0.028), and 18-month landmark analysis showed 86 % and 46 % (p = 0.015) in two groups, respectively. Conclusion. Despite the efficacy of JAK1/2 inhibitor ruxolitinib, the risk of myelofibrosis progression is not to be underestimated. Therefore, in DIPSS intermediate-2 and high-risk patients the issue about performing allo-HSCT should be promptly clarified.

Introduction: There is growing evidence of a connection between tumor clonal profile and its clinical impact. However, there is a lack of a feasible and reliable method for clonal profiling in actual clinical practice. Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder characterized by morphological dysplasia, cytopenia and a high risk of evolution to acute myeloid leukemia. The clinical outcome of myelodysplastic syndrome is greatly heterogeneous; therefore, specific examination of clonal profiles is needed to resolve the prognosis of patients with such complex disorders. Purpose: Development of a pipeline specifically for determining the clonal profiles in patients with myelodysplastic syndrome on the basis of target next-generation sequencing data. Results: The pipeline was developed and evaluated on a set of 35 patients with high-risk myelodysplastic syndrome. It is possible to use the target sequencing data in order to assess the heterogeneity of clonal profiles and characterize their genetic features. This approach allows you to identify the consistency between a specific individual profile and the disease prognosis, which can be critical for the treatment decision. Herein, the characterization and analysis of clonal profiles are presented. Practical relevance: The information about relation patterns between clonal profile characteristics (number of subclones, mutations-per-clone rate) and clinical outcome can be used by doctors in current practice for a more accurate therapy selection depending on the identified individual specificity of the disease.

Neuroblastoma (NB) is the most frequent pediatric extracranial solid tumor characterized by extreme biological heterogeneity with variable clinical course. Older age is an important risk factor. These patients may lack other common risk features but still have a chemoresistant disease with dismal prognosis. As there is currently no consensus on optimal treatment for patients with primary resistant NB, a number of clinical options is being explored including immunotherapy-based approaches. Immunotherapy with dinutuximab beta (DB) have proven its effectiveness as maintenance therapy. Allogeneic stem cell transplantation from haploidentical donor (haplo-HSCT) may be an effective consolidation in some cases. However, all forms of immunotherapy are much less effective in patients with large residual tumor. While there is no data on immune checkpoints inhibitors effectiveness in NB, some patients may benefit from this option as a part of complex immunotherapy strategy. Case presentation A 12-year old girl with gross paravertebral thoracic and abdominal tumor was diagnosed with undifferentiated neuroblastoma and bone metastases. While there was no response to several lines of chemotherapy, and only partial tumor resection was possible, the hematopoietic stem cell transplantation from haploidentical donor (haplo-HSCT) was performed as salvage therapy. Since there was only minor decrease in tumor volume with good dynamics by MIBG scan, additional post-transplant therapy was initiated. External beam radiotherapy was given for local control. The patient also received combined immunotherapy with DB and nivolumab. Currently, 3.5 years post haplo-HSCT, despite still gross residual tumor mass, it is MIBG-negative and shows signs of differentiation. Conclusion The combination of haplo-HSCT with post-transplant anti-GD2 and nivolumab may lead to a long-term response in an adolescent with primary resistant NB in spite of a large residual tumor mass.

The aim of this paper was to present evaluation and synthesis of data derived from a survey of Russian patients and physicians, performed as a part of the international Landmark study for the emerging market countries designed to specify problems and areas of concern in management of patients with chronic Ph-negative myeloproliferative neoplasms (MPN). The online survey forms were filled by 40 adult patients with Ph(-) MPNs (PV, 42.5%; MF, 37.5%; ET, 20%) and 30 physicians with sufficient experience in the Ph(-) MPNs treatment. As a part of this survey, patients and physicians answered questions related to perception of the disease symptoms and their impact on quality of life, daily activities and work productivity of patients, as well as their attitude to main treatment goals and various aspects of the patient-physician communication. The results revealed a number of differences between patient and physician perception of the disease and treatment, thus complementing the data of the Landmark Survey in other countries. It was shown that the patients with different variants of Ph(-) MPNs encounter sufficient disease-related difficulties in everyday life, impaired quality of life and reduced work productivity. Lack of coincidence revealed between the physician and patient assessment of the disease burden and treatment indicates the need for new ways of improving quality of clinical care provided to this category of patients. Further research in this area would be an important step towards implementation

В статье представлены результаты апробации программы индивидуальной коррекции нарушений письменной речи у младших школьников с задержкой психического развития на основе предварительной углубленной диагностики дисграфических ошибок, а также особенностей ряда познавательных процессов.

Contains fulltext : 248798.pdf (Publisher’s version ) (Open Access) Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.

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

Randomized multicenter trials in the area of hematopoietic stem cell transplantation (HSCT) face considerable challenges, therefore, their amount is relatively small. Most clinical guidelines are based on the data of multicenter registry studies or well-controlled prospective single-center non-randomized studies. To determine the criteria of a well-controlled single-center trial the results of which can be confi rmed by a multicenter analysis, the total of 44 groups of patients from 22 cooperative studies in collaboration with EBMT were analyzed. The results of these studies were compared with single-center data and the results of the planned studies of RM Gorbacheva Scientifi c Research Institute of Pediatric Oncology, Hematology and Transplantation. In 43 % of cases signifi cant diff erences were observed. The probability of diff erences did not decrease with an increasing number of patients in the single-center groups, but became higher (odds ratio 1.037; 95% confi dence interval 1.001-1.074; p = 0.046), which highlights the diff erences in methods of single- and multicenter trials. While analyzing the reasons for signifi cant diff erences the following necessary criteria for high-quali ty single-center trials in the area of HSCT were formulated: 1) conditioning regimens and graft-versus-host disease prophylaxis (if they are not subject of the study) need to be consistent with the most frequently used practices; 2) groups of patients should be status-homogeneous; 3) the trial must not include patients treated more than 5 years before the analysis; 4) patients should receive current antitumor therapy at pre- and post-transplantation stages; 5) each compared group should include more than 30-40 patients

A new simple universal form of the Kelvin equation, which can be used near the gas-liquid phase transition critical point, and the correction of the pressure and density for gas phase fluid outside the porous medium are taken into account for the oxygen meniscus effective curvature radius calculation at the phase equilibrium in mesoporous silica MCM-41, on the basis of the capillary evaporation and condensation experimental data.

The predictive value of graft composition and plasma biomarkers on the outcome of allogeneic HSCT is well known for conventional GVHD prophylaxis based on calcineurin inhibitors with or without antithymocyte globulin. Currently, there is limited data whether these results could be translated to post transplantation cyclophosphamide (PTCy). The prospective extension cohort of NCT02294552 trial enrolled 79 adult patients with acute leukemia in CR. Twenty-six received matched-related bone marrow (BM) grafts with single-agent PTCy and 53 received unrelated peripheral blood stem cell graft (PBSC) with PTCy, tacrolimus, and MMF. The grafts were studied by the flow cytometry, and plasma samples were analyzed by ELISA. In the cluster and major component analysis, we determined that transplantation from donors with high content of CD3, NKT, and CD16-CD56 + subpopulations in the PBSC grafts was associated with poor immunological recovery and compromised event-free survival (50% vs. 80%, HR 2.93, p = 0.015) both due to increased relapse incidence and non-relapse mortality. The significant independent predictor of moderate and severe chronic GVHD was the high prevalence of and iNKT, Vβ11, and double-positive cells in the PBSC grafts from young donors (HR 2.75, p = 0.0483). No patterns could be identified for BM grafts and for plasma biomarkers.

Aim. To assess the prognostic value of the mutation of DNA methylation genes, SF3B1, and TP53 in patients with myelodysplastic syndrome (MDS). Materials & Methods. Out of 35 MDS patients included into the trial 2 had multilineage dysplasia, 13 with excess blasts-I, 19 with excess blasts-II, and 1 had 5q-syndrome (criteria WHO 2016). In 30 patients primary MDS was identified, in 5 patients it was detected after prior chemo- or radiotherapy. 25 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to IPSS-R there were 1 low-risk, 5 intermediate risk, 17 high-risk, and 12 very highrisk patients. Hypomethylating agents were administered to 28 patients. Median age of patients was 49 years (range 18-80 years). Next-generation sequencing was applied for identifying somatic mutations in DNA methylation genes (TET2, IDH1/2, ASXL1, and DNMT3A) as well as in SF3B1, TP53, and RUNX1. Time to progression (TTP) was defined as the time from the initial diagnosis to the date of acute leukemia diagnosis. Allo-HSCT- or antitumor therapy-associated death was considered as competing risk. Results. Methylation gene analysis showed no mutation in 37 % of patients, in 40 % mutation was detected only in one of the genes, in 23 % mutation was identified in > 2 genes. SF3B1 mutations were reported in 23 % and TP53 in 11 % of patients. Median follow-up was 25 months (range 5-116 months). Univariate analysis showed no considerable differences in overall survival depending on mutation status. Median TTP in the group with allo-HSCT was not achieved, in the group without allo-HSCT it was 6 months (p = 0.0001). In patients with no SF3B1 mutation median TTP was 35 months, in patients with this mutation it was not achieved (p = 0.043). With ≥ 2 mutations in methylation genes median TTP was 12 months, in other cases it was not achieved (p = 0.024). In cases of TP53 mutation median TTP was 6 months, in cases without this mutation it was 43 months (p = 0.023). Multivariate analysis confirmed unfavorable prognostic value of TP53 mutation or ≥ 2 mutations in methylation genes in terms of TTP regardless of the drug treatment or allo-HSCT performed (hazard ratio 7.1; 95% confidence interval 2.6-19.6; p = 0.0001). Conclusion. The analysis of molecular markers yields additional data concerning the MDS prognosis. Further research is required to determine the prognostic value of molecular markers in clinical practice which will enable to individualize approaches to MDS treatment.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a radical method of chronic myeloid leukemia (CML) treatment. In the 1990s CML became the most frequent indication for allo-HSCT worldwide. CML treatment drastically changed after tyrosine kinase inhibitors (TKI) had been introduced into clinical practice. However, despite considerable progress achieved in treatment, low survival rate is observed in patients with CML either diagnosed at an advanced stage or characterized with resistance, TKI intolerance, and loss of response. For such patients allo-HSCT remains the only and the best treatment solution. The present article discusses current views on the importance of allo-HSCT for CML treatment in the era of extensive use of TKIs.

Chronic graft versus host disease (cGVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It significantly decreases survival and quality of life. The present study demonstrates retrospective data on extracorporeal photopheresis (ECP) in children with cGVHD. A total of 42 children with steroid-refractory cGVHD were enrolled in the study. The majority of patients had acute leukemia (n = 32, 76%). All patients received ECP as second (n = 18, 43%) or third (n = 24, 57%) line of therapy. Initial ECP schedule consisted of bimonthly regimen for two consecutive days with possibility of further tapering according to response. Any concurrent treatment administered before ECP could be continued if considered necessary. Complete response to ECP was registered in seven (17%) patients and partial response in 24 (57%). Overall response according to organ involvement was as follows: skin (n = 24, 75%), mucous membranes (n = 16, 73%), liver (n = 8, 80%), gut (n = 4, 80%), lungs (n = 2, 22%) and joints (n = 2, 67%). Five-year overall, progression-free and failure-free survival was 57%, 56% and 30%, respectively. Non-relapse mortality at 5 years was 14%. We didn’t observe any clinically significant complications in children that could be attributed to the procedure. ECP remains important and safe treatment option in children with cGVHD.

The use of semiconductor converters is relevant in various fields of industry and electrical engineering. Real objects and their parameters are included in the article and there is a description of rectifier circuits using mathematical formulas. The results of the research object models are presented in the work by using MatLab Simulink.

the risk of detecting incidents in the field of computer technology in Maritime transport is considered. The structure of the computer incident investigation system and its functions are given. The system of conducting investigations of computer incidents on sea transport is considered. A possible algorithm for investigating the incident using the tools of forensic science and an algorithm for transmitting the received data for further processing are presented.

The use of DC switching power supplies is relevant in various industries. DC switching power supply is considered as an example. The article contains a description of a DC power source with a power factor corrector. The results of the study of the object model considered in the article using MatLab Simulink are presented. The paper examines the characteristics of a pulse power supply for a personal computer. We also consider the possibility of using a power factor corrector to reduce the harmful effect of IIP on the supply network.

Power grids have become an integral part of the modern industrial world. Such grids are used not only to transport energy over long distances, but in many other applications (cars, homes, etc.) as well. Due to wide application of power grids, there are various specific solutions for each area of their application. This paper presents the main examples of the use of power grids and analyzes a number of key features using specific examples.

JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n = 274) or with (n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p = 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p = 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p = 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age > 58 years (p = 0.03) and HLA mismatch donor (p = 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10% to 15% of patients are cured by the procedure. Preclinical studies indicate that substitution of post-transplantation cyclophosphamide with bendamustine (PTB) in a prophylaxis regimen may be associated with an augmented graft-versus-leukemia (GVL) reaction. The aim of this study was to establish the optimal dose of PTB and evaluate the antileukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. In the prospective trial (NCT02799147), PTB was administered in doses of 140, 100, and 70 mg/m2 on days +3 and +4. Myeloablative conditioning with fludarabine and oral busulfan was provided to all patients. The first 12 patients received single-agent PTB, and subsequent patients received combination therapy with tacrolimus and mycophenolate mofetil (MMF). Inclusion criteria were acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to at least one induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. The study cohort comprised 22 patients with AML and 5 with ALL. Seven patients were enrolled in the 140 mg/m2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m2 and 70 mg/m2 groups. Primary refractory disease was documented in 41% of the patients, and secondary refractory was documented in 59%. The median blast count in the bone marrow at the start of the conditioning was 18% (range, 6% to 97%). Transplantation was performed with a matched sibling donor in 5 patients, a matched or mismatched unrelated donor in 15, and a haploidentical donor in 7. Engraftment was documented in 93% of the patients, including 89% with complete remission and 63% without measurable residual disease. After PTB prophylaxis, we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3 to 5 CRS in 44%. The most frequent clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation in 37%, and central nervous system toxicity in 26%. The development of CRS was associated with use of an HLA-mismatched donor (75% versus 20%; P = .0043). Classic acute GVHD was documented in 44% of the patients. Grade II-IV acute GVHD was associated with grade 3 to 5 CRS (67% versus 25%; P = .031). Moderate and severe chronic GVHD in the 100-day survivors were more often observed after single-agent PTB than after the combination immunosuppression (100% versus 18%; P = .002). A relatively low relapse rate was observed for this patient population. Three-year overall survival was 28% (95% confidence interval [CI], 13% to 46%), and event-free survival was 29% (95% CI, 13% to 46%). Nonrelapse mortality was 46% (95% CI, 25% to 64%), and the cumulative incidence of relapse was 26% (95% CI, 11% to 44%). No relapses were documented after day +100. There were no statistically significant differences among the dose groups (P = .3481); however, survival was higher in the 100 mg/kg group. Survival was higher in patients with AML compared with those with ALL (35% versus 0%; P = .0157). PTB represents a promising option to augment the GVL effect in refractory AML; however, the high CRS-associated mortality necessitates additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications, at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA-TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1-year overall survival (HR 0.3, 95% CI 0.13-0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99-4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA-TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified.

The paper shows a control system using artificial intelligence as an example of an induction motor with a frequency changer. Management is implemented using a fuzzy output controller. The optimal parameters of the fuzzy controller are determined. The calculations were carried out in the environment of dynamic modeling of technical systems SimInTech.

Aim. Using strict criteria, to assess incidence, pretransplant risk factors, and outcomes of severe "poor graft function" (sPGF), following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults. Materials & Methods. The study included 710 adult patients (median age was 31 years, range 18-70 years; 55 % male and 45 % female patients) with different hematological diseases and documented transplant engraftment after allo-HSCT from matched sibling (20 %), unrelated (67 %) and haploidentical (13 %) donors in the period from 2008 to 2016. Myeloablative and reduced-intensity conditioning regimens were administered in 30 % and 70 % of patients, respectively. The analysis was based on the following sPGF criteria: 2 or more lines of cytopenia (platelets < 20 x 109/L, absolute neutrophil count < 0.5 x 109/L, and hemoglobin < 70 g/L at any time after documented engraftment), complete or stable mixed donor chimerism > 90 %, and absence of relapse signs, rejection, and severe acute graft-versus-host reaction. The following factors were analyzed: age, sex, diagnosis, presence/absence of remission in acute leukemias, ferritin level, type of donor, HLA-match, blood group and sex match, graft source, number of transplanted CD34+ cells, and conditioning regimen. Multivariate analysis included parameters of univariate analysis with p < 0.05. Results. After allo-HSCT sPGF was identified in 103 patients with 2-year cumulative incidence of 15 % (95% confidence interval [95% CI] 12-18 %). In most cases sPGF developed during the 1st year after allo-HSCT (median 50 days). Bi- and trilineage cytopenia was found in 59 % and 41 % of cases, respectively. In multivariate analysis sPGF risk was associated with myelodysplastic syndrome, myeloproliferative disorders (hazard ratio [HR] 3.403; 95% CI 1.972-5.606; p < 0.0001), and haploidentical donors (HR 3.830; 95% CI 1.545-8.828; p = 0.001). The absence of remission at the time of allo-HSCT in acute leukemias and blood group incompatibility were of borderline significance. In almost half of the cases, sPGF had a poor outcome, including death from cytopenia-related complications, further relapses, and graft rejection. Prognosis of bilineage sPGF was more favorable than that of trilineage sPGF. Conclusion. The present large cohort study yielded the incidence and analyzed the structure of sPGF in adult patients with oncohematological diseases. In addition, the key pretransplant sPGF risk factors were identified. The results of the trial can serve to optimize the choice of therapy after allo-HSCT.

Background. Although the use of methotrexate (MTX) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) was compared in a large number of studies, the published results are contradictory. This fact provides ground for the present retrospective single-center trial comparing these two approaches in GVHD prophylaxis. Materials & Methods. The present study included 294 allo-HSC recipients with MTX prophylaxis and 172 allo-HSC recipients with MMF prophylaxis. 36 % of patients underwent matched related donor transplantation, and 64 % of patients received matched unrelated donor transplantation. Results. Univariate and multivariate analyses showed that probability of acute grade 2-4 GVHD was 36 % vs. 39 % (hazard ratio [HR] 1.297; 95% confidence interval [95% CI] 0.931-1.795; p = 0.122), grade 3-4 GVHD was 21 % vs. 25 % (HR 1.472; 95% CI 0.951-2.256; p = 0.05), and probability of chronic GVHD was 52 % vs. 55 % (HR 0.978; 95% CI 0.951-1.406; p = 0.91). In the MTX and MMF groups there were no significant differences in transplantation mortality (HR 1.173; 95% CI 0.797-1.708; p = 0.43), relapse incidence (HR 1.034; 95% CI 0.743-1.428; p = 0.84), overall survival (HR 1.087; 95% CI 0.825-1.433; p = 0.55), event-free survival (HR 1.108; 95% CI 0.854-1.437; p = 0.43), disease and GVHD free survival (HR 1.065; 95% CI 0.845-1.343; p = 0.59). Engraftment occurred earlier when MMF was used (p = 0.035). Administration of MMF instead of MTX was associated with lower probability of grade 3-4 toxic hepatitis (7 % vs. 31 %; p < 0.0001) and grade 3-4 mucositis (23 % vs. 45 %; p = 0.0002). Conclusion. The efficacy of GVHD prophylaxis using MMF is comparable with that of MTX, but MMF is associated with a better safety profile due to reduced incidence of severe liver toxicity and mucositis.