Background. The European Population Register EUTOS for CML includes data on adult patients (n = 2904) diagnosed with Ph-positive (Ph+) and/or BCR-ABL1-positive (BCR-ABL1+) chronic myeloid leukemia (CML) in 20 European countries during the period from 2008 to December 2012. Russia took part in this study, having contributed 6.8 % of CML patients to the total number of patients in the Register.

Aim. To estimate long-term treatment outcomes in patients with newly diagnosed CML in the Russian Federation in comparison with the data obtained for a pan-European population cohort of patients.

Patients and methods. The cohort under study consisted of 197 patients from 6 Russia regions, all of whom were diagnosed with a Ph+ / BCR-ABL1 + CML during the period from October, 1, 2009 to December, 31, 2012. The patients’ median age was 50 (18–82) years, with men and women being represented in approximately equal proportions.

Results. In the first line, 97 % and 3 % of the patients received Imatinib and 2nd generation tyrosine kinase (TKI) inhibitors, respectively. The response dynamics was as follows: 12 months after the treatment, a complete cytogenetic response and a major molecular response were achieved in 40 % and 20 % of the patients. The overall survival (OS) and progression-free survival rates in patients in Russia following 12, 24 and 30 months were 93 %, 87 % and 84 %, and 92 %, 87 % and 87 %, respectively. In Russia, the study was prolonged. By 80 months of observation, the OS of patients in the chronic CML phase with a low and high risk of the disease progression had been 88 % and 56 %, respectively. In the acceleration phase, the 5-year overall survival rate was 39 %.

Conclusion. An analysis of treatment outcomes in CML patients in a population-based non-selected sample indicates an increase in the survival of CML patients. However, problematic aspects of the therapy have been identified, along with a need for intensification of the treatment in patients with an unfavourable CML prognosis.

Introduction. Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria. AIP is caused by a deficiency in the third enzyme of the heme biosynthesis system — hydroxymethylbilanine synthase (HMBS) — and has a dominant inheritance type. However, the probability of the clinical manifestation of this condition in carriers of the mutation in the HMBS gene constitutes only 10–20 %. Thi s suggests that the presence of such a mutation can be a necessary but not a sufficient condition for the development of the disease.

Aim. To search for additional genetic factors, which determine the clinical penetrance of AIP using Whole-Exome Sequencing.

Materials and methods. Sequencing of the whole exome was performed using a TruSeqExomeLibraryPrepkit (Illumina) kit by an Illumina HiSeq4000 instrument for 6 women with API with known mutations in the HMBS gene. All the patients suffered from a severe form of the disease. As a reference, a version of the hg19 human genome was used.

Results. No common mutations were found in the examined patients. However, in each patient, functional variations were found in the genes related to detoxification systems, regulation of the heme biosynthesis cascade and expression of delta-aminolevulinic acid synthase (ALAS1) and in genes of proteins regulating nervous system. These variations require further study involving an extended number of patients with AIP manifestations and their relatives, who are asymptomatic carriers of disorders in the gene HMBS.

Conclusions. The results obtained have allowed us to formulate a hypothesis about a possible role of genetic defects in the penetrance of AIP, which determine the development of other neurological pathologies. This is evidenced by the presence of gene pathogenic variations in 5 out of 6 examined patients, defects in which are associated with hereditary myasthenia and muscle atrophy.

Introduction. No recommendations are currently available on the use of positron emission tomography / computer tomography (PET/CT) for evaluating the response to chemotherapy in patients with acute lymphoblastic leukosis / lymphoblastic lymphoma (ALL/LBL).

Aim. The aim of this research was to study the ability of tumour cells to accumulate radiopharmaceuticals during PET/CT in patients with ALL/LBL, as well as to evaluate the prognostic value of PET/CT results performed after completion of consolidation therapy with/without autologous hematopoietic blood stem cell transplantation (auto-HSCT) in patients with Ph-negative ALL/LLL who underwent therapy according to the protocols of a Russian research group ALL-2009/ALL-2016.

Materials and methods. PET/CT was performed in 3 patients with various variants of a newly diagnosed ALL before the onset of therapy and after the completion of induction therapy. In 10 patients with Ph-negative ALL/LLL, a PET study was performed after consolidation had been completed according to the ALL-2009/ALL-2016 protocol.

Results. The results of PET/CT in 3 patients with different variants of newly detected ALL/LBL were analysed. All patients showed a metabolic activity of 18F-FDG in all morphologically and immunohistochemically (immunophenotypically) confirmed lesions. An analysis of the PET/CT results in 10 patients with Ph-negative ALL/LBL after completion of consolidation therapy with/without auto-HSCT showed that all patients had achieved a PET-negative disease remission. With a median follow-up of 20.5 months (from 15 to 44 months), only one out of 10 patients demonstrated isolated neurorecurrence 10 months after achieving remission. The remaining 9 patients, under a median relapse-free survival rate of 19 months (from 14 to 43 months), demonstrated complete clinical and hematological remission.

Conclusion. Specific medullary and extramedullary lesions in ALL/LBL are capable of accumulating 18F-FDG in PET, which allows the method under study to be used for evaluating the completeness of remission in extramedullary lesions. The prognostic feasibility of PET/CT under the involvement of the central nervous system remains to be studied.

Introduction. Diffuse large B-cell lymphoma of postgerminal origin (ABC-DLBCL) and follicular lymphoma grade 3B (FL3B) are characterised by an aggressive course and resistance to chemotherapy (CT). Both diseases are characterised by the activation of genes of the post-terminal stage of B-cell differentiation and high expression of the MUM1 transcriptional protein. Lenalidomide in combination with R-CHOP improved the results of treatment in patients with ABC-DLBCL; however, about 40 % of them remain resistant to the therapy.

Aim. The aim of the study was to evaluate the efficacy and toxicity of the R-mNHL-BFM-90 protocol with lenalidomide (R2-mNHL-BFM-90), as well as to analyse possible causes of CT resistance in patients with ABC-DLBCL and FL3B.

Patients and methods. Over the period from October 2016 to December 2018, 8 patients with MUM1-positive DLBCL and FL3B were included in the research. All patients underwent a cytogenetic study of tumour samples. A mutational status of the TP53 gene was determined by Sanger sequencing.

Results. Patients received combination chemotherapy according to the R2-mNHL-BFM-90 protocol with lenalidomide at a dose of 25 mg/day, from the 1st to the 10th day of each course. Autologous hematopoietic stem cell transplantation was performed as a consolidation in three patients. After the end of the chemotherapy, a complete remission of the disease was achieved in all patients. Relapse developed in 1 patient with a mutation in the TP53 gene. With a median follow-up period of 11 months (1–23), event-free survival was 87 %.

Conclusions. The R2-mNHL-BFM-90 protocol has demonstrated a high efficacy and acceptable toxicity in patients with ABC-DLBCL and FL3B. The presence of a mutation in the TP53 gene is established to be an extremely unfavourable prognostic factor even provided intensive treatment protocols, thus requiring the development of alternative approaches to the management of such patients.

Introduction. Patients suffering from chronic myeloid leukemia (CML) demonstrate various degrees of therapeutic effect after treatment using tyrosine kinase inhibitors (TKI). The response is determined by the presence or absence of mutations in the BCR-ABL gene, as well as by the mutation type.

Aim. To establish the prognostic value of polymorphic variants of genes involved in the metabolism of TKI — CYP3A5 and hOCT1 — in patients with CML in the Republic of Bashkortostan (RB).

Materials and methods. A series of genetic studies was performed in 114 patients with a clinically and cytogenetically established diagnosis of chronic myeloleukemia (CML), among whom 55 and 59 were men and women, respectively, with the median age of 43 years, from 14 to 76 years. All the patients received TKI treatment according to national clinical guidelines and European Leukemia Net criteria. In order to compare patients with different treatment efficiencies, a group of 64 patients resistant to the therapy was formed. The groups under comparison were similar in gender and age. An analysis of polymorphic DNA loci of the hOCT1 and CYP3A5 genes was carried out using polymerase chain reaction of DNA synthesis and RFLP analysis followed by electrophoresis in 7–8 % polyacrylamide gel.

Results. No significant differences were found in the frequency distribution of alleles and genotypes of the rs776746 polymorphic locus of the isoenzyme P3A5 cytochrome p450 (CYP3A5) gene (p > 0.05) between CML patients with different TKI treatment efficiencies. When comparing the frequency distribution of alleles and genotypes of the rs683369 polymorphic variant in the (hOCT1) organic cation carrier gene, the *C*C genotype was established to be statistically significantly more frequent in patients with an optimal response to treatment compared to those treatment resistant. The frequency of occurrence of the *С*G genotype was almost two times higher in CML patients resistant to therapy and comprised 42.86 %, compared to the group of patients with an optimal response to TKI treatment with the value of 21.88 %.

Conclusions. In CML patients, in contrast to rs776746 of the CYP3A5 gene, the study of the rs683369 polymorphic locus of the hOCT1 gene has a prognostic value for assessing the efficacy of TKI treatment. The frequency of occurrence of the *C*G genotype was significantly higher in CML patients resistant to TKI therapy, while the G*G* genotype was less common and associated with the shortest life expectancy. The presence of the C*C* genotype was favourable for the overall survival of patients.

Introduction. Unification of guidelines and standards concerning requirements for HLA typing and assessment of the degree of HLA match between the recipient and the donor for different types of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is of a great importance.

Aim. To present contemporary requirements for the HLA typing of a recipient and a donor for allo-HSCT, to generalize recom mendations for assessing a required match degree of a recipient and a donor and to provide data on additional immunogenetic factors capable of improving the results of allogeneic hematopoietic stem cell transplantation.

General findings. Allo-HSCT appears to be an effective, and, in some cases, non-alternative treatment for many diseases of the blood system. The number of allo-HSCT types is constantly growing globally. Currently, an allogeneic hematopoietic stem cell donor can be selected for almost every recipient having indication for this type of therapy. Such a transplantation can be performed from an HLA-identical sibling, an HLA-match unrelated donor, a partially HLA-match unrelated donor, a relative haploidentical donor or cord blood. HLA match between the recipient and the donor present itself as an important factor affecting the results of allo-HSCT. The choice of a donor should involve a correct assessment the HLA match degree between the recipient and the donor, as well as consideration of additional factors that may affect the results of allo-HSCT.

Introduction. Ruxolitinib presents itself as a drug for the pathogenetic treatment of myelofibrosis (MF). New drugs have recently been developed for the treatment of MF. A search for optimal combinations of these drugs with ruxolitinib appears to be a logical approach to the development of MF therapy.

Aim. To summarize data on the use of ruxolitinib in combination with various drugs approved or currently being studied in terms of their applicability for MF treatment.

General findings. The review analyses data in publications retrieved from the PubMed and Elibrary.ru databases, including clinical cases, original research papers and reviews. We discuss preliminary results of clinical trials of various rational combination therapies, which have demonstrated a high efficacy for the forms of the disease untreatable with ruxolithinib monotherapy, e.g. bone marrow fibrosis and anemia. Combinations of ruxolithinib with azacytidine, panobinostat and α-interferon have shown the most promising results.

Introduction. Neonatal thrombocytopenia presents a serious clinical problem, due to the possible development of dangerous bleeding in the fetus and the newborn.

Aim. To elucidate pathogenesis, methods of laboratory diagnostics as well as markers and predictors of neonatal immune thrombocytopenia (NAIT).

General findings. NAIT develops due to a mismatch between the mother and the fetus in terms of platelet alloantigens (HPA, Human Platelet Alloantigens). The mother produces alloantibodies against alloantigen, absent on her platelets, but expressed on the platelets of the fetus and the father. Antibodies enter the bloodstream of the fetus, thus causing destruction of the platelets of the fetus/newborn. Neonatal transimmune thrombocytopenia (NTIT) is diagnosed in some newborns (20–40%) from mothers with immune thrombocytopenic purpura (ITP). In this case, the platelets of the fetus/newborn are affected by ITP maternal autoantibodies. The following methods are used to diagnose neonatal immune thrombocytopenia: measurement of platelet-associated immunoglobulins G (TA-IgG); determination of antiplatelet circulating (serum) antibodies (cAB); identification of cAB antigens. In the case of NAIT, the mother has neither thrombocytopenia nor an increase in TA-IgG; however, cABs are detected that react with the father’s platelets carrying conflicting HPA alloantigen. In newborns, thrombocytopenia and increased TA-IgG are observed. Alloimmune conflict is confirmed by genotyping HPA of maternal and child alloantigens, and/or by determining the specificity of cABs using alloantigens of HPA-typed donors. In the Russian population, the most common causes of NAIT are conflicts with respect to HPA-1a, HPA-1b (33 % and 33%, respectively) and HPA-15a/b (25%) conflicts. In the case of NTIT, ITP mothers demonstrate reduced platelet count and increased TA-IgG, and thrombocytopenic newborns shows increased TA-IgG. The predictor of NTIT is the presence of antiplatelet cAB in pregnant women with ITP.

Introduction. Neutrophils are the most numerous subpopulation of leukocytes circulating in the blood; they constitute the first line of defence of the innate link of the immune system.

Aim. To generalize basic concepts about phenotypic and functional heterogeneity of neutrophils.

General findings. According to contemporary concepts, this type of blood cells performs not only antimicrobial functions, but also participates in capture and destruction of various microorganisms, including such processes as phagocytosis and intracellular degradation, degranulation and formation of extracellular neutrophilic traps after the detection of microorganisms. Neutrophils are considered to be a phenotypically heterogeneous pool of blood cells featuring a significant functional variability. Under pathological conditions, they can differentiate into discrete subpopulations with va rious phenotypic and functional characteristics. They are capable of interaction with macrophages, natural killers, dendritic and mesenchymal stem cells, B and T lymphocytes or platelets. In addition, neutrophils exhibit vector properties with respect to cancerous tumours. They possess a high morphological and functional variability, being modulators of both inflammation and active triggers of immune responses. A search for molecular markers able to efficiently differentiate neutrophil phenotypes and establish the degree of their diagnostic specificity for various pathologies is of a particular importance.

Introduction. Screening and identification of anti-erythrocyte alloimmune antibodies in recipients is an important and necessary step in their testing before blood transfusion.

Aim. To formulate algorithms that could facilitate the process of pre-transfusion immunohematological testing.

General findings. Such a testing allows the development of post-transfusion reactions and complications to be avoided. The presence of alloantibodies of various specificities and autoantibodies in the test blood may complicate pre-transfusion testing and require the use of additional methods (adsorption, elution, etc.). The author has proposed an effective system of algorithms for conducting immunohematological studies, which can be used to identify patients at risk of developing immune post-transfusion complications and ensure an individual selection of compatible donor blood-transfusion products.

Introduction. Priapism is a prolonged painful erection lasting for more than four hours, which either persists after the termination of sexual stimulation or is not associated therewith. Priapism may be the first clinical manifestation of chronic myeloid leukemia (CML).

Aim. To describe a clinical case of ischemic priapism that occurred in a patient with a previously undiagnosed CML.

General findings. We present a clinical observation of ischemic priapism having lasted for 18 hours, which occurred in a patient with a previously undiagnosed CML. The diagnosis of CML was subsequently established on the basis of a study of peripheral blood and bone marrow. The therapeutic tactics consisted in an immediate puncture aspiration of blood from the corpora cavernosa and an intracavernous injection of a phenylephrine solution. After priapism had been relieved, an CML therapy was applied, which allowed the recurrence of priapism in the patient to be avoided.