Ffollicular lymphoma (FL) is one of the most common non-Hodgkin’s lymphomas in adults, while it is a diagnosis of exclusion in adolescents and children. Clinical manifestations of FL in children are represented by long-term asymptomatic lymphadenopathy, less commonly by extranodal areas involvement. treatment standards for FL in children have not been developed and may vary from observational tactics (with the radical resection of a single focus during a biopsy) to the use of radiation therapy and polychemotherapy. Pediatric type follicular lymphoma was first identified as a distinct variant in 2008 in the world Health organization classification of hematopoietic and lymphoid tissue tumors. Clinical, morphological (cytological type 3A), Immunohistochemical (absence of bcl2 expression in the center of the follicle) and cytogenetic (absence of t(14;18)(q32;q21)) features served as the reason for separation into an independent nosological variant. Despite the term “pediatric”, cases of pediatric type FL have been described in adults over 30 years of age. Most often, the disease is diagnosed in the early stages (I, II) and is characterized by a favorable prognosis. In children and adolescents, FL occurs not only of the pediatric type. we present a clinical case of a typical “adult” type FL (grade 1–2) in a 17-year-old patient. the cHop therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab resulted in a complete remission, which lasted more than 2.5 years.

   Background. Patients with B-cell lymphoma have an extremely unfavorable prognosis after relapse or in case of refractoriness to the first and consecutive lines of immunochemotherapy with the anti-CD19 CAR-T cells being the only therapeutic option to such patients. the manual preparation of anti-CD19 CAR-T lymphocytes was reproduced in the N. N. Alexandrov republican research and practical center for oncology and medical radiology (Minsk). Their safety was demonstrated.

   Aim. To estimate safety, tolerability and efficacy of the in-house CAR-T cells, including objective response rate, progression-free and overall survival.

   Materials and methods. The second generation anti-CD19 chimeric antigen receptor contained an anti-CD19 antibody scFv fragment, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. the coding sequence was cloned into the lentiviral vector S4. The cell product was obtained by expansion of CD4- and CD8-positive lymphocytes populations with IL-7 and IL-15 after initial activation and lentiviral transduction with vector S4. CAR-T cells were infused into 8 patients with refractory forms of B-cell lymphoma after the preliminary lymphodepleting chemotherapy. Persistence of CAR-T cells was assessed by flow cytometry. therapeutic efficiency was assessed by positron emission tomography-computed tomography with ¹⁸F-fluorodeoxyglucose.

   Results. Expansion of CAR-T cells with resulting b-cell aplasia was observed in all patients. the median of observation was 113 days (range 22–529 days). objective response rate was 100 %, complete remission was observed in 6 patients, partial response – in 1 patient. One patient died because of complications before the clinical response. Overall survival was 88 ± 12 %. cytokine release syndrome and neurotoxicity were not observed in 6 out of 8 patients despite a high tumor burden.

   Conclusion. Our study demonstrated efficiency and safety of the in-house CAR-T cells for the treatment of patients with refractory B-cell lymphomas.

The high efficacy of the currently used combined chemoradiotherapy for Hodgkin’s lymphoma not only significantly increased overall survival, but also made it possible for most patients to achieve the same quality of life as in a healthy population. at the same time, the problem of identifying late treatment complications, in particular cardiovascular the high efficacy of the currently used combined chemoradiotherapy for Hodgkin’s lymphoma not only significantly increased overall survival, but also made it possible for most patients to achieve the same quality of life as in a healthy population. at the same time, the problem of identifying late treatment complications, in particular cardiovascular diseases, remains an urgent problem, the timely diagnosis of which is an important task. the development of a second malignant neoplasm and the appointment of drug antitumor therapy with cardiotoxic agents necessitate a multidisciplinary approach. In the presented clinical observation, such tactics of patient management made it possible not only to timely identify late cardiovascular complications of Hodgkin’s lymphoma chemoradiotherapy, but also to conduct treatment for the second malignant disease with cardiotoxic agents with a positive antitumor effect.

   Multiple primary malignant neoplasms (MPMNs) is a complex process in which the development of 2 or more neoplasms simultaneously or after a certain interval is observed. MPMNs develop independently from each other within one or more organs. Many etiopathogenetic factors can cause MPMNs. Numerous studies have been conducted to study the effect of T-cell immunity on the development of this pathology. Today, there is a steady upward trend in the prevalence of mpmns, which, on the one hand, is due to more effective methods of early diagnosis, an increase in patient overall survival, and early antitumor therapy (chemotherapy, radiation therapy), on the other hand, this trend may be associated with pathology of T-regulatory cellular immunity. T-regulatory cells play a strategic role in the development of immune homeostasis, and their function is closely related to the occurrence of a wide range of pathologies, including autoimmune diseases and malignant neoplasms. The article presents a clinical case of a patient with a confirmed diagnosis: mpmn, immune thrombocytopenia (idiopathic thrombocytopenic purpura). On prednisolone therapy, remission was achieved for 2 metachronous tumors and a complete hematological response for immune thrombocytopenia was obtained. there were no signs of hemorrhagic syndrome and complications during prednisone therapy. It is planned to continue monitoring the patient for metachronous tumors by a hematologist, an oncologist at the place of residence, as well as at the center for orphan diseases of the Moscow Regional Research Clinical Institute named after M. F. Vladimirsky with control of platelets and general condition.

   Differentiation syndrome (DS) is a severe complication of acute promyelocytic leukemia and its treatment, which is one of the causes of high early mortality. the similarity of clinical manifestations of DS and other complications that may develop during acute promyelocytic leukemia therapy makes it difficult to diagnose ds. at the same time, untimely initiation of DS therapy with glucocorticosteroids can lead to the patient’s death. The only generally accepted risk factor for ds is initial leukocytosis. Specific markers confirming ds have not yet been found. A number of studies show that in patients with diagnosed DS, the expression of CD56, CD54, CD2, CD15, CD13, markers of immature granulocytes, β2-integrins was more often found on blast cells. exposure to tretinoin increased the expression of chemokine receptors, chemokines, and cytokines by blast cells and vascular endothelium. The influence exerted by atypical promyelocytes, due to their biological characteristics, on the coagulation system suggests an association between hemostasis state and ds development. However, the value of the above markers as predictors or signs of DS still needs to be tested, especially when it comes to non-chemotherapeutic treatment of acute promyelocytic leukemia with arsenic trioxide.

   Background. Aplastic anemia proceeds with bone marrow failure and is associated with immunological suppression of normal blood stem cells’ proliferation, which lead to bone marrow aplasia. autoimmune aggression and internal defects of blood stem cell that cause abnormal hematopoiesis are being actively studied. An important role in the pathogenesis of the aplastic anemia is played by instability of telomere length (TL). determination of the initial TL makes it possible to clearly differentiate between the aplastic anemia and dyskeratosis congenita. also, it helps to identify the group of patients with short telomeres for prediction of therapy response.

   Aim. To investigation the TL of various blood and bone marrow cells in patients with aplastic anemia before treatment.

   Materials and methods. The group of patients with aplastic anemia was investigated (n = 45). blood donors (n = 32) and bone marrow donors (n = 10) of different ages were included in the reference group. adult patients with dyskeratosis congenita (n = 5) were included in the comparison group. Relative and absolute tl was identified in peripheral blood and bone marrow mononuclear cells, monocytes, lymphocytes by flow-FISH technique (combination of flow cytometry and fluorescence in situ hybridization).

   Results. Relative and absolute TL was comparable in different blood and bone marrow cells in patients with aplastic anemia before treatment. TL in peripheral blood and bone marrow mononuclear cells wasn’t significantly differed in groups of patients with aplastic anemia and healthy donors. Telomeres in patients with dyskeratosis congenita were identified as “ultrashort” and were significantly shorter than in patients with aplastic anemia.

   Conclusion. Determination of TL in patients with aplastic anemia is modern examination method, which is a necessary step of differential diagnosis between aplastic anemia and dyskeratosis congenita, which is the disease from group of constitutional bone marrow aplasia. It is preferred to identify the TL in adult patients with aplastic anemia by the flow-FISH. It is necessary to investigate the TL to predict treatment response and to identify risks of developing adverse experiences, which include relapse and clonal evolution.

   Background. Immune thrombocytopenia (ITP), or idiopathic thrombocytopenic purpura, is a hematological autoimmune disease characterized by bleeding and an isolated decrease in platelet count <100 × 10⁹ / l. The decision to start treatment for ITP depends on several factors. The ITP treatment strategy is based on the clinical symptoms, with a focus on reducing the risk of severe bleeding and increasing platelet counts.

   Aim. To evaluate the efficacy of 2^nd line therapy with the thrombopoietin receptor agonist eltrombopag in patients with ITP.

   Materials and methods. 490 patients with ITP are under observation at the center for orphan diseases of M. F. Vladimirskiy Moscow Regional Research Clinical Institute. The present study included 186 patients with primary ITP after 1^st line glucocorticosteroid therapy. eltrombopag, a thrombopoietin receptor agonist, was prescribed as the 2^nd line of therapy.

   Results. The median platelet count prior to eltrombopag therapy in all patients was 27.5 × 10⁹ / l. after eltrombopag therapy, a significant (by 490 %) increase in platelet levels (median 135 × 10⁹ / l) and a complete response according to clinical recommendations were noted.

   Conclusion. Glucocorticosteroids (prednisolone, dexamethasone) remain the drugs of choice for the 1^st line of therapy. Treatment with drugs of this group in most cases allows achieving an optimal platelet level and preventing bleeding. In case of inefficiency, intolerance, occurrence of side effects, the appointment of thrombopoietin receptor agonists eltrombopag or romiplostim is recommended. therapy with eltrombopag at a dose of 50 mg daily for several weeks has been able to achieve an increase in platelet levels, correct hemorrhagic syndrome, reduce the number of side effects during first-line glucocorticosteroid therapy, and improve the patient’s quality of life.

   Hodgkin’s lymphoma (HL) is a unique lymphoma of b-cell origin, the tumor cells of which have lost the expression of main b-cell antigens. The standard immunophenotype of the tumor substrate, according to immunohistochemical studies, is characterized by the expression of such markers as CD15, CD30 and PAX-5, while tumor cells have a negative expression of CD3, CD19 and in most cases also CD20 and CD45 (or express this antigen rather weakly). The knowledge gained in recent years has increased the effectiveness of diagnosis, prognosis and treatment of LH. Flow cytometry, as a method of immunophenotyping in classical LH, was practically not used due to the difficulty of distinguishing single reed–sternberg–berezovsky tumor cells (RSB) and the tumor microenvironment (reactive background), which is very rich in cellular elements and is represented by T cells, B cells, eosinophils, histiocytes and plasma cells. However, in the recent past, several studies have successfully attempted to identify rsb cells using multiparameter flow cytometry during aspiration with a thin needle or biopsy of lymph node tissue to confirm or supplement immunohistochemical staining during primary diagnosis. Taking into account the very characteristic immunophenotype of RSB cells, the flow cytometry may become an additional diagnostic method of classical LH in the future. In this review, we summarize the data on the possibility of using the flow cytometry as an additional clinical diagnostic option in the primary diagnosis of classical LH.

   Aim. To study the glomerular filtration rate (GFR) dynamics during induction immunopolychemotherapy (PCT) in patients with newly diagnosed diffuse large B-cell lymphoma.

   Materials and methods. The study included 39 patients with newly diagnosed diffuse large b-cell lymphoma who received specialized treatment in oncohematology department of national medical research centre for oncology (Rostov-on-Don). Patients underwent induction pct according to the R-CHOP (rituximab, doxorubicin, cyclophosphamide, vincristine, prednisolone) regimen with accompanying therapy (allopurinol). blood sampling was carried out at 0, 24, 48, 72, 120 hours and 21 days of the 1^st PCT cycle. GFR was calculated using the SKD-epicre formula (chronic Kidney disease epidemiology collaboration creatinine-based). statistical data processing was carried out using the IBM SPSS statistics 23 program.

   Results. According to the gfr level before the start of chemotherapy (0 hours), the patients were divided into two groups: group a with GFR > 90 ml / min / 1.73 m² and group b with GFR < 90 ml / min / 1.73 m². In group a, there were no significant dynamic changes in the GFR level during PCT. Group B patients reacted more acutely to the administration of pct, which was manifested in an even greater decrease in the gfr level at 48 hours of PCT, and at 120 hours of PCT, the GFR approached the optimal values. on the 21^st day from the start of the 1^st pct course, the studied indicator returned to its initial values at 0 hour. further, the patients of these groups were divided into subgroups depending on the disease stage: group a consisted of 12 people with stages I–II and 15 people with stages III–IV. In group B, there were an equal number of patients with stages I–II and III–IV – 6 people. In group a, in patients with stages I–II and III–IV before the start of PCT (0 hours) and during PCT, there were no differences in the GFR level dynamics. In group B, patients with stages I-II and III–IV had similar GFR before the start of PCT, and during treatment, they reflected the previously noted general group trend in GFR level dynamics.

   Conclusion. The study found that in patients with initially low GFR level, a further, even more pronounced decrease in GFR during pct is observed. at the same time, the absence of significant differences in GFR level depending on disease stage allows us to conclude that the leading role is not so much the stage of the disease and tumor volume, but rather the initial functional status of the kidneys in the development of renal dysfunction in patients with diffuse large B-cell lymphoma during R-CHOP therapy.

   Background. Classical Hodgkin’s lymphoma is a B-cell lymphoproliferative disease, the tumor substrate of which is Berezovsky–Reed–Sternberg cells, characterized by CD30, PAX-5, CD15 expression and the absence of CD3, CD45. In some cases, tumor cells express CD20. modern anticancer therapy has increased the survival probability for most patients, not only with early but also with advanced stages of classical Hodgkin’s lymphoma. Such successes are mainly due to the distribution of patients into prognostic groups and the choice of an appropriate treatment regimen. tumor infiltration of the bone marrow suggests assigning patients to the advanced stages group, followed by the choice of an intensive therapy program.

   Aim. To determine the bone marrow involvement frequency according to positron emission tomography combined with computed tomography (PET/CT), with ¹⁸F-fluorodeoxyglucose (FDG) and bone marrow trephine biopsy (bmtb), to compare the results obtained with primary tumor immunophenotype and bone marrow cellular composition, and to identify of prognostic risk factors.

   Materials and methods. The study included 107 patients with newly diagnosed classical Hodgkin’s lymphoma, who underwent a diagnostic examination at the moscow research institute of oncology named after P. A. Herzen – a branch of the National Medical Research Center for Radiology and the “Lapino” clinical Hospital from 2015 to 2022, followed by anticancer therapy and further follow-up. Morphology of the primary tumor biopsy specimen in all patients and immunohistochemical (IHC) study using a wide panel of monoclonal antibodies (CD15, CD30, CD3, CD45, CD20, PAX-5 anti-gens; in some cases epstein–barr virus proteins expression) in most cases were performed. All patients underwent a morphological and / or IHC study of BMTB and the majority underwent aspiration biopsy and PET/CT with ¹⁸F-FDG.

   Results. The most common histological variant of classical Hodgkin’s lymphoma was nodular sclerosis (86.9 %). The majority of patients (51.4 %) were assigned to the advanced stage prognostic group. bone marrow tumor infiltration was statistically significantly more frequently diagnosed during PET/CT with ¹⁸F-FDG compared with the results of the BMTB – in 27.1 % and 12.1 % of cases, respectively (p < 0.05). when comparing the results of both diagnostic methods, it was found that in 17.1 % of cases, bone marrow infiltration, detected during PET/CT, was not confirmed by IHC examination of the trephine biopsy. In addition, it was found that the majority of cases with CD20^+/± and CD15^+/± expression in the primary tumor were observed in the group of patients without bone marrow involvement. when assessing the cellular composition of bone marrow aspirates, it was revealed that in patients with bone marrow tumor infiltration, an increase in cellularity and megakaryocytes number along with a decrease in the plasma cells number is observed.

   Conclusion. The results suggest further study of bone marrow immunomorphological features in order to identify prognostic factors and search for new therapeutic targets. a more extended analysis of bone marrow aspirate immunomor-phological characteristics using new modern diagnostic methods, minimal residual disease status as a surrogate marker seems to be relevant and necessary to confirm the depth of the antitumor response achieved. Detection of CD20^+/±- and cd15^+/±-Berezovsky–Reed–Sternberg cells according to primary tumor IHC analysis indicates a low probability of bone marrow tumor infiltration, but further analysis is required on a large clinical and laboratory material.

   During aging phenotypic changes in the hematopoietic system occur, and possible reason of these changes can be accumulation of gene mutations in hematopoietic stem cells or early blood progenitors. Although these mutations are mostly neutral, some may give hematopoietic stem cells and progenitor cells a proliferative advantage. In this case clonal hematopoiesis will arise, which is characterized by the formation of a genetically distinct subpopulation of blood cells. Clonal hematopoiesis may become a basis for the development of hematologic malignancies, such as acute myeloid leukemia. Clonal hematopoiesis associated genes which are most commonly mutated in acute myeloid leukemia patients are DNMT3A, TET2 and ASXL1. The prognostic significance of these gene mutations currently remains a subject of study.

Background. Tumor cell proliferation in acute myeloid leukemia (AML) may manifest with high leukocyte counts. In our work, we evaluate the association of high leukocyte counts with individual mutations, as well as their total contribution to the development of leukocytosis in AML. The results obtained should improve our understanding of pathogenic mechanisms leading to the leukocytosis in AML.

Aim. To study the genetic landscape of AML with leukocytosis.

Materials and methods. The laboratory data of 214 AML patients admitted to the National Medical Research Center for Hematology (Moscow) from 2010 to 2022 were retrospectively examined. Real-time PCR, capillary electrophoresis and NGS (next generation sequencing) methods were used to detect mutations of FLT3, NPM1, CEBPA, IDH1/2, DNMT3A, TET2 genes, and CBFB::MYH11, RUNX1::RUNX1T1 chimeric gene transcripts.

Results. Mutations of the FLT3 gene (odds ratio 5.45; p < 0.0001), inv(16)/CBFB::MYH11 (odds ratio 10.03; p = 0.0009) are most associated with leukocyte counts higher than 30 × 10⁹ / L in the debut of AML. Translocation t(8;21)/RUNX1::RUNX1T1 and adverse cytogenetic aberrations, such as -5/del(5q); -7 / del(7q); -17 / abn(17p), complex and monosomic karyotype were significantly associated with leukocyte counts lower than 30 × 10⁹ / L at the time of disease manifestation (p < 0.0001). In the group of patients with intermediate cytogenetic risk bearing only IDH1/2, DNMT3A, and TET2 gene mutations, leukocyte counts at AML debut were significantly lower, whereas the most pronounced leukocytosis was observed in patients with a combination of driver mutations with IDH1/2, DNMT3A, and TET2 gene mutations or FLT3, NPM1, and CEBPA gene mutations.

Conclusion. In addition to the individual effect of certain genetic lesions and cytogenetic aberrations on the proliferative potential of tumor cells, there is a total contribution of various types of genetic events to the development of leukocytosis in AML. High leukocyte counts at the time of AML manifestation in patients with intermediate cytogenetic risk can serve as an indirect marker of the presence of a large number of genetic aberrations with a combination of IDH1/2, DNMT3A, and TET2 gene mutations or FLT3, NPM1, and CEBPA gene mutations.

   Minor histocompatibility antigens (MiHAs) are polymorphic peptides on the cell surface derived from self-proteins that are capable to induce an immune response during allogeneic hematopoietic stem cells transplantation. Their presentation occurs in the context of the certain major histocompatibility complex (HLA – human leucocyte antigen) alleles. One of the most common HLA alleles is HLA-A*02:01. Accordingly, for a significant number of donors and recipients pairs, it is possible to use the MiHAs presented in the HLA-A*02:01 as a target for relapsed leukemia therapy. This review discusses the main known MiHAs presented in the context of HLA-A*02:01, their characteristics and approaches used for identification. The described approaches may be used to search for new MiHAs for immunotherapy.

   Oncological and hematological diseases associated with HIV infection continue to cause discussions among foreign and domestic researchers, clinicians, doctors, medical workers. The ongoing world globalization and modernization, environmental degradation have a detrimental effect on the health of citizens, which can be seen in virus mutations, high morbidity and a decrease in the social level in the Russian Federation and in the world. Oncological and hematological diseases associated with HIV infection are growing in the Russian Federation, but scientists do not stop at the results achieved, improving methods, treatment and therapy. As part of this study a statistical analysis of oncological and hematological diseases associated with HIV infection for 3 years (2019–2021) in Russia is carried out in order to trace the percentage of the medicine’s level, treatment’s effectiveness and deaths. A detailed analysis shows the decrease in deaths from HIV infection which pays attention the work of specialists in the Russian Federation.

   The purpose of this study is to identify a key method for the treatment of oncological and hematological diseases in HIV infection in Russia.

   The objective is to study the effectiveness of existing methods of treatment.

   Research methods – clinical, functional, microbiological and morphological.

   Currently no therapy of acute lymphoblastic leukemia is conceivable without L-asparaginase drugs, with its antileukemic effect by extracellular asparagine depletion, thus preventing its admission to leukemic cell. Besides high antitumor effect, L-asparaginase drugs have side and toxic effects, such as hypersensitivity reactions, thrombosis, pancreatitis / pancreatic necrosis, and hepatotoxicity. For L-asparaginase safety profile improvement a technology of pegylation was lay down and PEG-aspargase drug produced. This drug has less toxic effects and recommended as first-line therapy of acute lymphoblastic leukemia. Drug monitoring for assessment the effectiveness and toxicity of L-asparaginase is optimal. Such therapy individualization helps for L-asparaginase dose finding and decrease frequency and severity of side effects.

   On June 24, 2023, an Expert Council was held in St. Petersburg, during which leading experts in the field of hematology discussed current achievements and answered a number of unresolved issues of targeted therapy of paroxysmal nocturnal hemoglobinuria (APG) in order to further improve treatment results in Russia. During the Expert Council, the following aspects of targeted APG therapy were considered: • criteria for the suboptimal response of patients with APG to therapy with inhibitors of the 5th component of complement (C5); • efficacy and safety of the use of pegcetacoplan in APG in patients with insufficient efficacy of inhibitors of the C5 component of complement; • vaccination issues before starting therapy with complement inhibitors and the possibility of conducting treatment with pegcetacoplan at home.