Introduction. Anaplastic large cell lymphoma (ALCL) is characterized by clinical, morphological and immunohistochemical heterogeneity. Both intensive block regimens and programs similar to those used in the treatment of acute lymphoblastic leukemia (ALL) are used in therapy. Taking into account the prognostically unfavorable effect of the expression of T-cell markers by tumor cells, a protocol ALCL NII DOIG 2003 was developed, which takes into account not only risk groups, but also immunophenotypic features of the tumor substrate.
Aim. To evaluate the treatment effectiveness of children with ALCL according to the protocol ALCL NII DOIG 2003 in comparison with the standard protocol NHL-BFM 95.
Materials and methods. The study included 100 patients with newly diagnosed ALCL who received treatment from 2000 to 2023 in 5 federal and regional pediatric oncohematology departments. The patients were divided into 2 groups depending on the protocol of therapy: I group — 48 patients treated with protocol ALCL NII DOIG 2003; II group — 52 patients treated according to the NHL-BFM 95 protocol. The basis of the protocol ALCL NII DOIG 2003 was made up of high-intensity block regimes similar to those used in the treatment of high-risk T-precursor ALL. A comparative assessment of the overall, event-free and relapse-free survival of patients was carried out depending on the therapeutic protocol using the SPSS 21.0 program. Results. The 10-year overall survival rate in patients from I group was 95.3 ± 3.3 %, II group — 82.0 ± 5.4 % (p = 0.037). 10- year event-free survival in I group was 95.3 ± 3.3 %, II — 68.6 ± 6.5 % (p = 0.001). 10-year relapse-free survival in I group of patients was 97.3 ± 2.7 %, while in the II group — 74.4 ± 6.4 % (p = 0.003).
Conclusion. The obtained results indicate the high effi ciency of a differentiated, immuno-oriented approach to the treatment of ALCL with the ALCL NII DOIG 2003 protocol, making it possible to achieve signifi cantly higher survival rates of patients compared to the standard treatment protocol.

Introduction. Congenital thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening genetic disorder characterized by recurrent episodes of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction due to the defi ciency or dysfunction of the ADAMTS13 enzyme. Despite the availability of clinical and laboratory diagnostic criteria the diagnosis remains challenging due to a wide range of diseases with similar appearance.
Aim: to analyze the clinical manifestations and treatment results of identifi ed cases of congenital TTP at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.
Methods. This article reviews 11 clinical cases with congenital TTP genetically confi rmed or with typical clinical and laboratory signs.
Results. Clinical and laboratory signs of TTP are highly variable and nonspecifi c, which was observed in the described cohort of patients. One of the trigger factors is often an acute respiratory viral infection, and stabilization of the disease can occur after transfusions of blood components. A delay of diagnosis can often lead not only to a delay of correct therapy, but also to the prescription of wrong therapy. The main diagnosis confi rmatory method was a molecular genetic test, which was carried out in 8 cases. All patients diagnosed with congenital TTP were successfully treated with FFP therapy.
Conclusion. Early diagnosis of TTP is diffi cult due to the lack of specifi c clinical manifestations and easily accessible laboratory tests

Introduction. As part of the implementation of the federal project Development of a network of national medical research centers and the introduction of innovative medical technologies, one of the activities of the National Medical Research Center for Hematology (Center) is the analysis of the staffi ng of medical organizations (MO) of the constituent entities of the Russian Federation (RF) by hematologists.
Aim — to analyze the dynamics of staffi ng by hematologists of MO in the RF.
Materials and methods. Data from the Federal State Statistics Service (Rosstat) — Federal Statistical Observation Form No. 30 “Information about a medical organization” of the constituent entities of the Russian Federation for 2012–2020, reference books of the Central Research Institute of Organization and Informatization Health of the Russian Ministry of Health in the Russian Federation, information obtained from the results of on-site events of the National Medical Research Center for Hematology, including expert assessments were used.
Results. The hematological service is organized in all subjects of the RF, with the exception of the Chukotka and Nenets Autonomous Okrug, Republic of Kalmykia and Altai, as well as the Jewish Autonomous Region. As of December 31, 2021, 1,594 hematologists work in the constituent entities of the RF, of which 460 specialists are in outpatient care and 1133 specialists in hospital settings. Analysis of the availability of full-time positions of hematologists per 10,000 populations in the Russian Federation in dynamics for 2012–2020 revealed fl uctuations in the values of this indicator from 0.06 to 0.17. The largest “failure” in the provision of hematologists occurred in 2014 in almost all federal districts (FD) of the Russian Federation. Only the Urals FD maintains the stability of the indicator of availability of these specialists. Over the past 3 years, there has been an increase in the number of full-time positions of hematologists, while the staffi ng of individuals reduced due to the lack (increase) of new employees and slightly offset by an increase in the coeffi cient of internal part-time work. Thus, the highest combination coeffi cient was noted in 2020 in the Ural (1.49) and Siberian (1.45) FD, the lowest in the North-Western FD (1.09). In accordance with the legal act regulating the activities of the hematology service, the standard for calculating the positions of outpatient hematologists is 1 doctor per 200 thousand of the population, however, the provision of full-time positions for the outpatient stage of care remains not achieved (2021 — 0.92 per 200 thousand); at least 731 doctors are needed against the existing 456 specialists. The staffi ng standard of the department of hematology corresponds to one medical position per 10 beds. Compliance with regulations regarding the formation of the staffi ng table of the inpatient unit was noted in 95% of the constituent entities of the Russian Federation.
Conclusion. The issues of personnel shortage of hematologists are relevant. The shortage of hematologists in the Russian Federation indicates the lack of attractiveness of remuneration and indicates the need for management decisions to be made by the Government of the Russian Federation and executive authorities of the constituent entities of the Russian Federation aimed at developing mechanisms for maintaining the human resource of hematologists in the healthcare system.

Introduction. In Russia, within the framework of the GIPAP program, in the period from 2001 to 2007 at the National Medical Research Center for Hematology, imatinib therapy was initiated in 235 patients in the chronic phase of chronic myelogenous leukemia (CML).
Aim: to analyze the long-term results of therapy in patients with CML who started imatinib therapy as part of the GIPAP program.
Methods. A retrospective analysis of the results of therapy was performed in 235 patients with СР CML, who received imatinib under the GIPAP program from 2001 to 2007 at the National Medical Research Center for Hematology. The protocols for therapy and monitoring of the residual disease of patients at various time intervals were determined by the clinical recommendations relevant at that time in the conditions of real clinical practice and the possibilities of the patient’s region of residence. Overall survival and survival without discontinuation of imatinib therapy, univariate and multivariate analysis of overall survival were performed. The cumulative incidence of responses was calculated. An analysis of response factors, the probability of death from concomitant diseases and death from CML was carried out.
Results. The median follow-up of living patients at the time of analysis was 17.3 years (IQR 15.5–18.5). 70 (30 %) patients died, with the median time to death from the start of therapy being 7.8 years (IQR 3.7–13.6). The overall 10-year, 15-year and 20-year survival rates were 82 %, 74 % and 62 %. The cause of death in 43 cases (61%) was the progression of CML to the phase of acceleration or blast crisis and death out of remission for an unspecifi ed cause. 27 (39%) patients died from causes not related to CML. Patient age at initiation of imatinib therapy, length of time from diagnosis to initiation of imatinib therapy, and Sokal and ELTS risk groups at disease onset were identifi ed as signifi cant for survival by univariate analysis. Multivariate analysis showed independent predictive value for overall survival for age at initiation of imatinib therapy, length of illness before imatinib treatment, and ELTS risk group at disease onset. Among patients who died from CML progression, the proportion of patients who did not achieve CCyR for the entire period of therapy before death was 83% (35/42), while among patients who died from concomitant diseases, the proportion of patients without CCyR for the entire period of therapy was 11 % (p < 0.0001). The median duration of imatinib therapy was 11.4 years (0.8–21 years). 40 people died during imatinib therapy, 103 patients are alive and continue therapy with imatinib, 92 patients received at least one second-generation of Tyrosine kinase inhibitors (TKI) (TKI2), of which 62 people are alive and continue treatment with TKI. No more than two lines of TKI therapy were received by 49 (21 %) patients, and three or more lines were prescribed to 43 (18 %) patients. The median duration of therapy after switching to TKI2 was 7.8 years (0.1–15.6 years). Overall 15-year survival after switching to TKI2 was 59 %. On therapy with imatinib, during the entire observation period, complete cytogenetic response (CCyR) was achieved in 171 patients (73 %), another 18 patients (8 %) achieved CCyR for the fi rst time after switching to TKI2. Major (MMR) and deep molecular response (DMR) were achieved with imatinib in 129 (56 %) and 124 (53 %) patients, with TKI2 TKI2 therapy in 38 (16 %) and 33 (14 %) patients, respectively. Multivariate analysis showed an independent predictive value of only the time period from diagnosis to the start of imatinib treatment for achieving molecular responses to TKI therapy.
Conclusion. After 20 years of monitoring patients on TKI therapy, we still cannot say that survival in CML is comparable to the survival of normal population. Long-term follow-up confi rms the fact that tumor reduction to at least the level of CCyR is the most signifi cant surrogate marker associated with a reduced risk of death from CML. Timely diagnosis of the disease, rapid initiation of targeted therapy and the fastest possible induction of cytogenetic and molecular responses is a very important mechanism for reducing the risk of resistant course and progression of CML.

Introduction. The RH system includes major antigens D, C/c and E/e encoded by two closely related RHD and RHCE genes. Correct identifi cation of Rh antigens in both donors and recipients is the key to proper transfusion practice. However, there are cases when Rh antigens cannot be detected by standard serological typing. For example, –D– phenotype has no expression of C, c, E, and e antigens on the surface of erythrocytes due to various genetic rearrangements in the RHCE gene.
Aim: to present a study of a family where two siblings have a defi cient -D-phenotype with a normal rhesus phenotype in the parents
Materials and methods. A comprehensive study of family N., including parents and two sons was conducted. Initially, an unusual phenotype -D- was identifi ed in the siblings, who are currently donors. All family members identifi ed themselves as Tatars. Serology tests were performed using gel cards. Genomic DNA of family members, as well as cDNA of siblings, was examined by allele-specifi c PCR, exon-scanning assay, and Sanger sequencing. In addition, copy number analysis was performed to identify rearrangements in the RHD and RHCE genes.
Results. During serological typing of siblings, only the D antigen was revealed, while the C/c and E/e antigens were absent. Molecular genetic analysis suggested that the cause of the phenotype –D– in the brothers was a hybrid allele RHCE-D(3-8)- CE in homozygous status, forming a haplotype inherited from each parent with the normal RHD allele. The sequence of the fi rst two exons in the hybrid allele corresponded to RHCE*C allele. The parents were heterozygous for the identifi ed allele, so the expression of C/c and E/e antigens was not altered.
Conclusion. Two donors with the –D– phenotype were assessed by comprehensive study. Identifi cation of the genetic causes of such variants in recipients is necessary to ensure safety during transfusion of erythrocyte-containing blood components. Genotyping of donors with Rh-defi cient phenotypes is also highly recommended in order to predict the molecular structure of Rh antigens.

Introduction. In addition to the clonal nature of the development of erythrocytosis, there are other causes, such as germinal mutations in genes of proteins responsible for the development of familial inherited erythrocytosis (EPOR, VHL, EPAS1, EGLN1, etc.).
Aim. To conduct the analysis of mutations in the EPOR, VHL, EPAS1 and EGLN1 genes associated with the familial erythrocytosis ECYT1-4 among JAK2- and CALR-negative patients.
Materials and methods. The study included 50 JAK2- and CALR-negative patients of Krasnoyarsk Krai with erythrocytosis of unclear etiology. Analysis of mutations in the EPOR, VHL, EPAS1 and EGLN1 genes, responsible for the development of familial erythrocytosis was conducted with the use of the Sanger sequencing. A mass parallel sequencing study was also performed for 12 patients.
Results. The Sanger sequencing analysis of EPOR, VHL, EPAS1 and EGLN1 revealed any of the genetic variants in 22 of the 50 patients studied. Of all the variants identifi ed in the coding regions of the genes surveyed that result in amino acid substitutions, the following were of biggest interest: 1) two mutations in the VHL gene (rs28940298 and rs5030821) associated with the development of Chuvash polycythemia (ECYT2); 2) rs12097901 variant in the EGLN1 gene associated with altitude adaptation and increasing haemoglobin levels, but with no pathogenetic relevance for erythrocytosis according to ClinVar; and 3) one mutation in the EPOR gene not previously described in literature. According to the results of the NGS study, 12 somatic and 4 putative germinal variants were identifi ed in 5 out of 12 patients.
Conclusion. The possibility of conducting a comprehensive molecular genetic study in order to identify new mutations or those already described in the literature in genes associated with familial erythrocytosis could make a signifi cant contribution to the diagnosis of patients with absolute erythrocytosis.

Introduction. Von Willebrand disease (vWD) is a hereditary disorder of the blood coagulation system caused by a quantitative and/or qualitative defect of Willebrand factor (vWF), the pathogenetic principle of treatment of which is substitution therapy with combined concentrates of factor III and vWF. When bleeding foci of gastrointestinal angiodysplasia appear, hemostatic replacement therapy may not be effective.
Aim: to present a clinical observation of the cessation of bleeding from gastrointestinal angiodysplasia after the use of a growth factor inhibitor in a vWD patient.
Main fundings. A clinical case of treatment of a type III vWD patient with recurrent bleeding from foci of gastrointestinal dysplasia is presented. In order to stop bleeding, a course of therapy with a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (bevacizumab) was performed. 6 injections of the drug were administered, with a single dose being 400 mg. The interval between injections was 2 weeks. After bevacizumab therapy for 12 months, there were no cases of bleeding, although no hemostatic drugs were administered.

Introduction. Hairy cell leukemia (HCL) is a chronic indolent B–cell lymphoproliferative disease with a good response to treatment in most cases. However, despite successful treatment, there remains a group of patients with a resistant/recurrent course of the disease, a short remission after treatment, and with contraindications to standard therapy. The use of the RASRAF- MEK-ERK pathway inhibitor in the V600E marker mutation of the BRAF gene may prove to be an effective treatment option for complicated/resistant cases of HCL.
Aim — to present the results of the use MEK-kinase inhibitor trametinib in the treatment of HCL.
Main findings. The MEK-kinase inhibitor trametinib was used at a dose of 1 mg/day for 3 months in three patients. In two patients trametinib was used as preliminary stage before the main course of treatment with cladribine. In one patient with a resistant/relapsing course of HCL, trametinib monotherapy made it possible to achieve a good partial remission, and the treatment continues without a decrease in the quality of life.
Conclusion. Trametinib can be used as a preliminary stage before analogous purine treatment in patients with HCL without the BRAF V600E mutation, in a case of deep neutropenia or infectious complications, and as the main antitumor therapy in patients with resistant/recurrent HCL. Trametinib is effective in the absence of the MAP2K1 mutations. Trametinib monotherapy can be effective at a reduced dosage (1 mg/day or 1 mg every other day).

Introduction. Primary immune thrombocytopenia (ITP) is an autoimmune disease caused by the production of antibodies to the membrane structures of platelets and their precursors — megakaryocytes, which causes not only increased destruction of platelets, but also inadequate thrombocytopoiesis, characterized by isolated thrombocytopenia below 100.0×109/L and the presence/absence of hemorrhagic syndrome of varying severity.
Aim: to present modern recommendations for the diagnosis and treatment of ITP
Basic information. The recommendations are based on the experience of Russian and international experts, the leadership of the international working group on the study of primary immune thrombocytopenia, and recommendations of the European and American Societies of Hematology using new data on the development and course of ITP. Approaches to the treatment of the disease using new drugs from the group of thrombopoietin receptor agonists are present