Background. Currently, targeted therapy is the most promising for the treatment of myelofibrosis (MF). Today, the results of many years of experience with the use of ruxolitinib, including outside randomized trials and the identification of predictors of its effectiveness are important.

Aim. To evaluate the results of long-term ruxolitinib therapy in patients with primary and secondary MF resistant to standard treatment and compare the effectiveness of MF targeted therapy in patient groups depending on age, gender, clinical, laboratory and morphological parameters.

Materials and methods. The prospective study included 206 patients (95 (46 %) men and 111 (54 %) women aged 18–84 (mean 64) years) with MF in the chronic phase who received ruxolitinib: 154 (75 %) with primary MF, 39 (19 %) – with post-polycythemic, 13 (6 %) – with post-thrombocythemic. The median duration of chronic myeloproliferative disease from diagnosisto prescription of ruxolitinib was 75 (1–432) months. According to DIPSS (Dynamic International Prognostic Scoring System), 15 % of patients were classified as high risk, 35 % as intermediate-2, 33 % as intermediate-1, and 17 % as low-risk. 44 % of patients had MF3, 49 % – MF2, 7 % – MF1. 71 % of patients had JAK2 V617F mutation, 3 % – MPL, 19 % – CALR, and in 7 % triple negative status was detected.

Results. The median duration of ruxolitinib therapy was 24 (1–116) months. Clinical and hematological response at 1 month: complete and partial response – 14 %, clinical improvement – 20 %, stabilization – 57 %; at 3 months – 21, 34, 36 %, at 1 year – 34, 21, 34 %, respectively. No response was obtained in 18 % of patients. The median allele burden of JAK2 V617F during observation decreased more than twice from the initial value in half of the patients. The median of progression-free survival (PFS) from the start of ruxolitinib therapy was 28 months, the median of overall survival (OS) has not been achieved. PFS at 1 year of treatment was 68 %, at 2 years – 56 %, at 3 years – 46 %, at 5 years – 32 %, OS – 87, 75, 68, and 54 %, respectively. Among many factors analyzed before starting ruxolitinib therapy, the following ones had statistically proofed significance for PFS: age, DIPSS risk level,therapy with hydroxycarbamide, interferon, white blood cell count, platelet count, hemoglobin level, and degree of fibrosis. For OS,the following factors were significantly important: age, risk level according to DIPSS,type of MF, interferon therapy, white blood cell count, platelet count, hemoglobin level, and degree of fibrosis.

Conclusion. The long-term effectiveness of ruxolitinib therapy for primary and secondary MF has been demonstrated. Gender, age, clinical, laboratory, and morphological prognostic factors of ruxolitinib therapy efficiency in MF have been identified.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a decrease in platelet count, which often leads to bleeding. Evidence suggests that low platelet counts in ITP are the result of multiple factors, including impaired thrombocytopoiesis and changes in the immune response leading to platelet destruction. ITP is a heterogeneous disease with a course that is difficult to predict. In a significant number of cases, ITP becomes chronic, requiring long-term maintenance treatment, which leads to an increased risk of hemorrhagic complications and a decrease in quality of life. A deeper understanding ofthe etiology and pathogenesis ofthis disease makesit possible to identify potentialtherapeutic targets for the development of new effective treatments. This review summarizes recent advances in understanding the ITP pathophysiology, evaluating current therapeutic strategies and methods for predicting therapy response.

Background. Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors achieve durable optimal responses. Loss of the achieved molecular response is observed in 15–30 % of patients. Mutations in the BCR::ABL kinase domain are one of the most common mechanisms for the development of resistance to tyrosine kinase inhibitors.

Aim. To conduct a retrospective analysis of the BCR::ABL kinase domain mutational profile in patients with CML observed at the Russian Research Institute of Hematology and Transfusiology from 2012 to 2023. To assess the impact of mutations type and number on the rate of achieving a major molecular response (MMR). To study the risk of MMR loss depending on the therapy line and existing mutational status.

Materials and methods. 1831 patients with CML were examined at different times. The mutational status of the BCR::ABL kinase domain was analyzed by direct Sanger sequencing. A standard cytogenetic study was carried out using GTG banding technology with the analysis of at least 20 metaphase plates.

Results. Mutations in the BCR::ABL kinase domain were identified in 27.6 % of the total studied patients. The most common mutation, 6.3 % in the overall group or 22.7 % among patients with mutations, was the T315I mutation. Additional chromosomal aberrations (ACAs) were detected in Ph-positive cells in 20.5 % of patients, in Ph-negative clones in 3.9 % of cases (p = 0.0001). The frequency of ACAs detection did not statistically significantly differ (p = 0.25) between patients with BCR::ABL mutations (23.5 %) and with a negative mutation status (17.7 %), and the presence of mutations in the kinase domain did not correlate with ACAs in Ph-positive clones (p = 0.73). However, the frequency of T315I mutation detection in Ph-positive cells had significant differences: 40.9 % in combination with ACAs and 21 % without ACAs (p = 0.032). Patients with the T315I mutation had significantly worse MMR than patients with mutations in other BCR::ABL regions (p = 0.04) and patients without mutations (p = 0.02). The probability of MMR achieving did not differ significantly between patients with different numbers of BCR::ABL mutations (p = 0.14). Loss of MMR occurred more often in patients with mutations (p = 0.04) and not depend on the line of therapy (p = 0.03).

Conclusion. For complete monitoring and optimal choice of therapy, CML patients require not only monitoring of BCR::ABL relative expression level, but also standard cytogenetic and analysis of the mutational status.

Background. Acquired aplastic anemia (AA) is a non-tumor disease of the blood system and the pathogenesis is based on immune dysregulation directed against own hematopoietic stem cells, which leads to the development of bone marrow aplasia. Some modern research is directed to the study of intrinsic defects of hematopoietic stem cells, and one of which is the change in telomere length. Several large studies have shown the association of telomere shortening in AA patients with decreased overall survival, poor response to immunosuppressive therapy (IST), high rates of relapse and clonal complications.

Aim. To study the influence of the initial telomeric DNA regions length in AA patients on the disease course.

Materials and methods. 43 adult patients with acquired AA without previous pathogenetic therapy were included in the study. IST was performed according to a standard protocol including the use of hATG and cyclosporine. Flow-FISH was used as the method for measuring relative telomere length, and peripheral blood mononuclear cells were used as the study material.

Results. Telomere length determined before IST did not differ between non-severe and severe AA, but there were significant differences depending on disease duration (p = 0.032). Initially short telomeres correlated with a lower rate of achieving hematologic improvement (53 % vs. 80 %; p = 0.059). In addition, significantly worse results were obtained in achieving partial and complete remission in patients with initially short telomeres compared to those with initially long telomeres (37 % vs. 62 % and 5 % vs. 23 %, respectively; p <0.05). There was a tendency to increase the frequency of new chromosomal aberrations in patients with shorter telomere length.

Conclusion. The results obtained do not contradict previous studies and show the association of a decrease in baseline telomere length with poor response to IST and a high risk of clonal complications. The determination of telomere length should be used both in differential diagnosis between the acquired disease and congenital bone marrow failure syndromes, and for timely choice of patient management tactics (IST or allogeneic hematopoietic stem cell transplantation).

The introduction of the complement component C5 inhibitor eculizumab has radically changed the prognosis and quality of life of patients with paroxysmal nocturnal hemoglobinuria. Up to 30 % of patients develop only a suboptimal response to C5 inhibition. One reason for this is activation of extravascular hemolysis, due to opsonization of erythrocytes with fragments of the C3 component. Pegcetacoplan, the first ever registered C3 inhibitor, is aimed at solving this problem.

In Russia, 2 patients received pegcetacoplan as part of a phase 3, randomized, open-label, active-comparator controlled trial PEGASUS. The analysis includes data from the first year of therapy: the run-in period (pegcetacoplan 1080 mg SC twice weekly in addition to the current dose of eculizumab, 4 weeks), the randomized controlled period (both patients were randomized to eculizumab monotherapy, 16 weeks), and the open-label period of pegcetacoplan therapy (32 weeks). Data from the extension study to evaluate the long-term safety and efficacy of pegcetacoplan are also presented. The duration of follow-up on pegcetacoplan therapy in both patients exceeded 4 years.

Background. Chronic lymphocytic leukemia (CLL) is a slowly progressive malignant disease that results in uncontrolled proliferation and accumulation of B-lymphocytes in the blood and bone marrow, and is the most common form of leukemia in Western countries. Patients with CLL and chromosome 17 deletion or TP53 mutation who progress after treatment with immunological, chemotherapeutic, and targeted agents (e. g., ibrutinib) have a poor prognosis and represent a population with an unmet medical need. Clinical trial results have shown that venetoclax, a selective, bioavailable, orally administered inhibitor of the anti-apoptotic B-cell lymphoma protein, induces apoptosis in CLL cells and provides an alternative treatment option for CLL patients, either alone or in combination with rituximab.

Aim. To evaluate the efficacy and safety of venetoclax in relapsed/refractory CLL in Russia routine clinical practice.

Materials and methods. A multicenter observational prospective study P19-569 FORTE was conducted in Russia. The patients were monitored throughout the 24-month treatment period. During this period, the treating physician assessed the objective treatment response according to the International CLL Working Group criteria. The last minimal residual disease result obtained during treatment and the method of its assessment (if performed) were also to be recorded. The primary endpoint was the overall response rate at 12 months after initiation of treatment.

Results. The study included 71 previously treated patients with relapsed/refractory CLL. The median age was 63 (35–83) years. All patients were white/Caucasian, and the majority were male. According to baseline characteristics, the study population included patients who had previously received intensive therapy: the median number of previous therapy lines was 3 (1–8). A number of factors associated with the risk of an unfavorable prognosis have been identified in patients, including chromosome 17 deletion or TP53 mutation.

12 months after the start of treatment, the overall response rate was 68.6 %, complete remission was observed in 41.4 % of patients; in the venetoclax monotherapy subgroup these parameters were 63.3 and 42.9 %, in the venetoclax with ibrutinib subgroup – 81.0 and 38.1 %, respectively. 24 months after the start of treatment, the overall response rate was 71.4 %, complete remission was observed in 45.7 % of patients; in the venetoclax monotherapy subgroup these parameters were 67.3 and 46.9 %, in the venetoclax with ibrutinib subgroup – 81.0 and 42.9 %, respectively. During 24 months of treatment, minimal residual disease was assessed in 28 (40 %) patients, of whom 14 (50 %) had undetectable disease in the peripheral blood or bone marrow.

There were 23 deaths during the study. The median overall survival was not achieved. No laboratory signs of tumor lysis syndrome were detected in patients. The majority of adverse events leading to death were CLL progression; the 2nd largest group were cases of SARS-CoV-2 infection.

Conclusion. The obtained data confirm the possibility of venetoclax therapy in relapsed/refractory CLL patients.

Background. The study of bone marrow involvement is a necessary step in disease staging, both in non-Hodgkin lymphomas and in the case of Hodgkin lymphoma (HL). The standard assessment of bone marrow lesion is carried out based on immunohistochemical examination of bone marrow trepanobioptate, and recently computer technologies (positron emission tomography combined with computed tomography) have been introduced to assess bone marrow involvement. At the same time, immunological methods for detecting tumor cells using multicolor flow cytometry are more available. In addition, they allow for detailed study of the tumor bone marrow microenvironment.

Aim. To evaluate the immunomorphological features of bone marrow in HL and the possibility of identifying specific bone marrow lesions using flow cytometry.

Materials and methods. The study included the analysis of 107 bone marrow samples. The samples were obtained from 107 patients with various variants of classical HL, diagnosed and treated at the Lapino Clinical Hospital and the P.A. Herzen Moscow State Medical Institute from 2018 to 2022.

Results. The features of bone marrow lymphocytes subpopulation in patients with classical HL are shown.

Conclusion. An immunological assessment of bone marrow involvement degree was carried out, data from flow cytometry and immunohistochemical examination of trephine biopsy specimens during primary diagnosis were compared, and the features of bone marrow lymphocytes subpopulation were evaluated. The interrelation of these factors at the diagnostic stage in classical variants of HL was studied. At the end of treatment, the primary immunological data (the degree of bone marrow involvement) were compared with the results of the positron emission tomography combined with computed tomography.

Aim. To evaluate the acute myeloid leukemia (AML) treatment efficacy in adults in Moscow real clinical practice according to the Moscow Cancer Registry data.

Materials and methods. We retrospectively collected data from the Moscow Cancer Registry on Moscow permanent residents who were primary diagnosed with AML from January 2019 to November 2023. The effectiveness of antitumor therapy was assessed by the complete remissions rate, relapses, deaths, and 3-year overall and relapse-free survival. Data analysis performed as of 01.12.2023.

Results. According to the Moscow Cancer Registry, from 01.01.2019 to 01.12.2023, the diagnosis of AML (except for acute promyelocytic leukemia) was established in 752 patients with a median age at the time of diagnosis of 64 (19– 94) years. In the studied sample, females slightly predominated: women – 56.6 % (n = 426), men – 43.4 % (n = 326). Of all patients included in the study, 36 % (n = 275) received intensive chemotherapy, while 57 % (n = 427) received low-intensity chemotherapy, and the remaining 7 % (n = 50) patients received best supportive care. Early mortality (first 60 days) in the total group was 16 % (n = 123), 20 % (n = 149) of patients were refractory to the therapy. Complete remission was achieved by 63 % (n = 473) of patients: 82 % (n = 225) of them received intensive chemotherapy, 58 % (n = 248) – low-intensity chemotherapy. Relapses occurred in 41 % (n = 194) of 473 patients who achieved complete remission. In the first remission, allogeneic hematopoietic stem cell transplantation was performed in 11 % (n = 79) of patients. With a median follow-up of 30.1 months, the 3-year overall survival in total group was 27 % (95 % confidence interval 23–32), and the 3-year relapse-free survival was 44 % (95 % confidence interval 37–51).

Conclusion. The main problem in the treatment of adult AML patients remains high induction mortality and limited opportunities for allogeneic hematopoietic stem cell transplantation in real clinical practice, which emphasizes the need to develop transplant centers in Moscow.

Background. Renal failure (RF) is unfavorable prognostic factor for the multiple myeloma (MM) patients, negatively affecting overall survival. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is associated with an increased risk of HSCT-related complications and mortality, which may limit its implementation in MM patients with RF, especially in patients with severe RF requiring hemodialysis.

Aim. To analyze the effectiveness and adverse events of high-dose chemotherapy followed by auto-HSCT in newly diagnosed MM patients with severe RF requiring hemodialysis.

Materials and methods. We analyzed the data of 7 newly diagnosed MM patients with severe RF requiring hemodialysis, who received auto-HSCT.

Results. Complete remission achieved 2 (28.6 %) patients, very good partial remission – 4 (57.1 %) patients, partial remission – 1 (14.3 %) patient on the 100th day after auto-HSCT. Complete renal response achieved 6 (85.7 %) patients, 1 (14.3 %) patient remained a minimal renal response. Auto-HSCT led to an improvement in both hematological and renal responses in 1 (14.3 %) patient, hematological response – in 2 (28.6 %) patients. With a median follow-up of 19 months, median progression-free survival and overall survival were 43 and 81 months, respectively. In the early post-transplant period, febrile neutropenia (71.4 %) and grade III–IV mucositis (71.4 %) were most often diagnosed. In the study group of patients, there was no auto-HSCT-related mortality.

Conclusion. Auto-HSCT is an effective and safe method of treating newly diagnosed MM patients with severe RF requiring hemodialysis.

Follicular lymphoma is one of the most common non-Hodgkin’s lymphomas in adults. One of the rather rare variants of follicular lymphoma is pediatric follicular lymphoma. This variant, despite the name, is diagnosed not only in children, but also among young adults. Pediatric follicular lymphoma is characterized by early (I, II) stages, the absence or weak BCL2 expression, and the predominant absence of t(14;18)(q32;q21) translocation. Treatment tactics vary widely from radical surgical tumor resection with subsequent follow-up to chemoimmunotherapy with rituximab.

This article presents a clinical case of advanced pediatric follicular lymphoma (stage III) in a 5-year-old patient. Using a combined treatment approach (surgery followed by immunochemotherapy) allowed to achieve a complete metabolic response which lasts more than a year.

Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia <0.5 × 10⁹ /L after successful initial engraftment, which cannot be explained by tumor relapse, infections or chemotherapy toxicity.

In this report, we present a clinical case of a 57-year-old woman with newly diagnosed diffuse large B-cell lymphoma with multiple lesions of the skeletal bones and lymph node involvement on both sides of the diaphragm. A feature of this case of diffuse large B-cell lymphoma was the secretion of monoclonal IgGκ and plasmacytoid differentiation of tumor cells. Firstline therapy with 6 cycles of R-CHOP was unsuccessful. A complete metabolic response according to positron emission tomography combined with computed tomography (PET/CT) was obtained after 2 cycles of second-line R-DHAP therapy, followed by myeloablative consolidation and transfusion of 16.9 × 10^6/kg CD34⁺ autologous hematopoietic stem cells. The patient was discharged from the hospital on day +15 with stable restoration of hematopoiesis. The pancytopenia and aplasia of bone marrow hematopoiesis developed across 3 months after auto-HSCT. For secondary GF, the patient received G-CSF, transfusions of blood components, and treatment similar to that for aplastic anemia (cyclosporine 5 mg/kg plus eltrombopag). A partial hematological response was obtained within 9 months, and a complete response by 24 months of therapy. According to PET/CT data 36 months after auto-HSCT, the patient had a local increase in the level of ¹⁸F-fluorodeoxyglucose fixation (maximum standardized uptake value 3.33), possibly of an inflammatory nature, in the body of the L4 vertebra on the background of bone cement after vertebroplasty performed at the onset of the disease. In addition, monoclonal secretion of IgGκ persists in the absence of immunomorphological evidence of bone marrow involvement.

In conclusion, the article discusses the possible causes of the monotonous monoclonal IgGκ secretion and presents a literature review of known GF treating methods.

Background. Mastocytosis is a rare myeloproliferative disease based on clonal hematopoiesis of mast cells, with accumulation of mast cells in various tissues and organs. The cutaneous mastocytosis is common in the pediatric population and, in general, progression to aggressive forms is not typical. In the adult population, there is systemic mastocytosis with a predominance of indolent and smoldering forms according to the literature, but there aren’t epidemiological data for the Russian Federation.

Aim. To evaluate the results of primary diagnostics obtained during the examination of 70 patients with suspected systemic mastocytosis.

Materials and methods. The histological studies of the skin and bone marrow, mutations in the c-kit gene in the bone marrow and serum tryptase level were examined in the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation in accordance with WHO 2017 criteria.

Results. The diagnostic results of 70 patients with suspected mastocytosis, the diagnosis was confirmed in 71.4 % (n = 50) of patients, of which systemic mastocytosis accounted for 82 % (n = 41). The 2 most common categories were identified: indolent systemic mastocytosis in 23 (56 %) patients and widespread forms in 15 (36.5 %), with a median time of diagnosis of 12 and 5 years, respectively.

Conclusion. The late diagnosis is noted in all subgroups of systemic mastocytosis.

Evaluation of bone marrow cytogenetic abnormalities in myelodysplastic syndrome is of great importance for confirming the clonal disease nature, determining the prognosis and choosing treatment tactics. Cytogenetic abnormalities are detected in 40–70 % of patients with myelodysplastic syndrome, and the variety of these abnormalities reflects the disease characteristics.

This article describes the clinical follow-up of a patient with a myelodysplastic neoplasia with blast excess 1 and trisomy of chromosome 14.

Recent advances in the diagnosis and understanding of follicular lymphoma (FL) pathogenesis have had a significant impact on therapeutic tactics. The life expectancy of patients has increased significantly. Currently, the 5-year overall survival of FL patients achieved 90 %, and its median is approaching 20 years. However, FL remains an incurable disease with periods of remission and relapse, requiring multiple therapy courses throughout the patient’s life.

The main problem is the treatment of patients with refractory/relapsed forms, especially after 3rd line of therapy, as well as with a primarily resistant course and early (in the first 2 years) relapses. Therefore, despite the indolent FL course in most patients, there remains a need for new drugs that can ensure increased treatment efficacy with minimal toxicity and simultaneously maintain a high quality of life, mainly in the presence of primary refractoriness, early progression and in later lines of therapy. In recent years, new targeted drugs have been studied – phosphoinositide 3-kinase, enhancer of zeste homolog 2 inhibitors, as well as immunological drugs (CAR-T therapy (CAR – chimeric antigen receptor) and bispecific antibodies).

The article presents the possibilities of treatment for refractory/relapsed FL as 3rd and subsequent therapy lines.

Background. Aplastic anemia (AA) is a non-tumor and rare disease of the blood system, characterized by deep pancytopenia due to the development of bone marrow aplasia with immune-mediated damage of hematopoietic stem cells. Research results indicate the presence of antigenic effects leading to pathological activation and dysregulation of the T cells in the bone marrow with increased production of pro-inflammatory cytokines that damage hematopoietic stem cells. The triggering factor that initiates the cascade of immune reactions is currently unknown. The high efficiency of immunosuppressive therapy (IST), which allows achieving remission in the majority of AA patients, is evidence of the immune genesis of the disease. The pathogenesis of AA is currently being actively studied. The participation of T cell subpopulations in immune response is beyond doubt, but the issues of their significance in the AA pathogenesis have not been fully studied. A more detailed understanding of the AA development mechanisms is necessary for the development of long-term effective treatment.

Aim. To investigate the T cells subpopulation in bone marrow of AA patients during IST.

Materials and methods. The study included 41 patients over 18 years of age with newly diagnosed acquired AA without previous IST. Treatment was carried out according to a protocol including horse antithymocyte globulin and cyclosporine. Flow cytometry was used to detect T cell subpopulations. Bone marrow examination was performed at three time points: initially, 3 and 6 months after initiation of combined IST.

Results. Multidirectional changes in the T cell subpopulations ratio before the start of IST were found in all AA patients included in the prospective study: most patients had a higher proportion of effector CD4⁺ and CD8⁺ T cells (61 and 83 % of patients, respectively), memory CD4⁺ T cells (63 % of patients), and a lower proportion of naive CD4⁺ and CD8⁺ T cells (81 and 51 % of patients, respectively) compared to donors (p <0.05). The abnormal T cell subpopulation ratios that cause abnormal immune response are most pronounced in the very severe form of AA. When responding to treatment, no significant changes in T cells subpopulation were found either before the start of IST or 6 months after compared with donors. In the absence of treatment response, a higher proportion of effector CD4⁺ and CD8⁺ T cells, memory CD4⁺ T cells, and a lower proportion of naive CD4⁺ and CD8⁺ T cells were detected compared to donors already before the start of IST (p <0.05). Of all cytometric parameters, a significant relationship was obtained between effector CD8⁺ T cells dynamics and response to treatment (p = 0.040). The number of these cells at the onset and control points significantly correlated with the response to IST. In patients who have not responded to treatment by the 3rd month from IST initiated, there is a further increase in effector CD8⁺ T cells number, despite the IST continuation, which dictates the need to intensify IST in the shortest possible time (between the 3rd and 6th months) in these patients, namely, a 2nd course of equine antithymocyte globulin and continuation of cyclosporine therapy or individual consideration of alternative treatment (allogeneic hematopoietic stem cell transplantation).

Conclusion. Studying the T cells subpopulation dynamics, in particular effector T cells, allows us to determine the tactics of further treatment in the early stages of IST in order to select the optimal treatment program for each AA patient.

Background. Mycosis fungoides (MF) is classified as an orphan disease. Due to the rarity of pathology, and until recently the absence of an expert group and a specialized reference center for cutaneous lymphomas in Russia, possible treatment options for MF are presented by listing them without recommendations on the preferred indications for one or another option. This creates difficulties in choosing treatment methods and assessing their effectiveness.

Aim. To characterize current treatment methods and their results in MF patients who were observed or received consultative and diagnostic care at the National Medical Research Center for Hematology.

Materials and methods. The study included 210 patients: 115 with early disease stages and 95 with advanced stages.

Results and conclusion. The most common treatment options were for early stages – local therapy, interferon therapy and systemic chemotherapy (CT), for advanced stages – combination therapy with interferon (+ PUVA therapy, methotrexate), interferon monotherapy and systemic CT. The frequency of systemic chemotherapy use in all lines of MF treatment was 21 %. When integrating statistical analysis using the probability of achieving an antitumor response, switching to 2nd line therapy, and accumulated incidence, the negative results of using chemotherapy in the MF treatment were clearly demonstrated.

For the first time in Russia, a real practical situation of the applied MF treatment options is presented on our own large sample of patients. As the first line of therapy, the most common options were immunotherapy and phototherapy, however, in 12.4 % of cases, the use of systemic CT was registered, which is unjustified and leads to a decrease in the time to the next line of treatment and an increase in the cumulative incidence of adverse events. As a result of the use of non-chemotherapeutic approaches (interferon, etc.), the 3-year relapse-free survival rate is about 40 %, after chemotherapy – 9.4 %. Secondand third-line therapy provided more varied options, including combination treatment with interferon and methotrexate, as well as gemcitabine monotherapy, targeted therapy with brentuximab vedotin, and epigenetic therapy in the 3rd line. Studies with targeted agents in this patient population have demonstrated improved clinical outcomes, highlighting the need for their early use to achieve the best results.

In current immunotherapy, a promising direction is therapy using chimeric antigen receptor T cells (CAR-T). Among malignant hematological diseases, even at advanced stages and resistant/recurrent forms, the use of CAR-T demonstrates high efficiency. The observed clinical success in patients with hematologic malignancies not only determines the ever-increasing list of indications for the use of CAR-T in this group of patients, but also motivates the study of this treatment method in solid oncology and autoimmune diseases. This review examines the history of the emergence and development of CAR-T, the path from the idea of creation to registration to clinical use.

Plasmoblastic lymphoma is a rare, aggressive B-cell malignancy with poor long-term survival. Plasmoblastic lymphoma occurs most commonly in patients infected with human immunodeficiency virus (HIV), but cases associated with solid organ transplantation have also been reported, less commonly plasmoblastic lymphoma registers in immunocompetent patients. The disease is more common in male patients (75 %) aged from 8 to 62 years (median age 50 years), and most often the tumor lesions are localized in the oral cavity. Rare localizations of plasmoblastic lymphoma include pleura, testicles, mammary glands, lungs, and skin. As casuistic areas of lesions, the central nervous system can be noted.

The article describes a clinical case of HIV-positive pediatric patient with rare plasmoblastic lymphoma of chiasmosellar zone. The disease was complicated with secondary hypocorticism and hypotyreosis, a deficiency of somatotrophic hormone and diabetes insipidus.

Background. Patients with acute lymphoblastic leukemia (ALL) have been the most vulnerable group of patients at risk of severe and extremely severe COVID-19 throughout the coronavirus pandemic. Secondary immunodeficiency due to acute leukemia, as well as antitumor treatment, predisposes to the development of a more severe infection, as well as long-term SARS-CoV-2 persistence even after complete regression of COVID-19 symptoms. Thus, although after the emergence of the SARS-CoV-2 Omicron variant, coronavirus infection began to occur predominantly in a mild form, COVID-19 in ALL patients remains an urgent problem.

Aim. To assess hospital survival of patients with ALL and concomitant coronavirus infection, to identify predictors of death and to evaluate the impact of program antitumor therapy on the outcome in this cohort of patients.

Materials and methods. A retrospective analysis of ALL patients hospitalized in City Clinical Hospital No. 52 with coronavirus infection from February 2020 to December 2022 was conducted. Diagnosis and treatment of patients were carried out in accordance with valid at the time of hospitalization temporary guidelines “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)”. Univariate and multivariate regression analyses were performed to identify predictors of mortality in patients with ALL and COVID-19. Survival analysis was performed using the Kaplan–Meier method. A p <0.05 was considered statistically significant.

Results. The study included 60 patients with ALL and concomitant coronavirus infection (30 men and 30 women). The median age was 42 years. Extremely severe coronavirus infection was observed in 25 % of patients in 2020–2021 and in 5 % of patients in 2022. Forty five patients received chemotherapy a month before hospitalization for COVID-19, 23 patients – during hospitalization. In-hospital mortality was 25 % (11 patients in 2020, 4 patients in 2021). The cause of death in 9 (60 %) cases was severe coronavirus infection; 4 (27 %) patients died as a result of severe bacterial complications, 2 (13 %) – due to ALL progression. In multivariate regression analysis, the following predictors had a statistically significant impact on the outcome: ALL relapse, absence of seroconversion at the time of outcome (anti-SARS-CoV-2 IgG level at the time of outcome <50 U/mL). When analyzing the impact of chemotherapy administered a month before or during hospitalization due to coronavirus infection, statistically significant values were not obtained for any of the factors.

Conclusion. Considering the obtained results and international recommendations for the treatment of ALL patients with COVID-19, the decision on antitumor treatment for ALL patients when SARS-CoV-2 RNA is detected by polymerase chain reaction in an oropharyngeal swab should be made individually depending on the patient’s age, clinical manifestations of coronavirus infection, ALL status and the antitumor therapy phase. In addition, given the reduced antiviral response in ALL patients, special attention should be paid to the prevention of SARS-CoV-2 infection, and in case of disease development, passive immunization methods (virus-neutralizing monoclonal antibodies) should be considered as antiviral therapy.

Allogeneic hematopoietic stem cells transplantation is an effective method for the treatment of hematologic malignancies and other blood system diseases. Infections caused by human 6A and 6B herpes viruses are one of the leading causes of complications and mortality in hematology patients after allogeneic hematopoietic stem cell transplantation, especially in the first 100 days after transplantation. This review discusses the clinical features of infections caused by human herpes viruses 6A and 6B, their impact on the development of post-transplant complications, including graft-versus-host disease and graft failure, as well as methods of prevention and treatment.

Background. One of the most common symptoms of multiple myeloma (MM) is pain. Bone pain is observed in 60– 80 % of patients at the disease onset. Neuropathic pain syndrome is also often found in MM.

Aim. To characterize the pain syndrome in MM at the disease onset and various therapy stages.

Materials and methods. From January 2019 to October 2021 a retrospective single-center study included 105 patients with newly diagnosed symptomatic MM (49 men, 56 women) aged from 26 to 83 years (median 58.5). Induction therapy in all patients was performed with bortezomib-containing regimens. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was performed in 44 patients. The Fisher–Freeman test was used to analyze contingency tables.

Results. Pain syndrome of varying severity at the onset of MM was observed in 83 % of patients. The median time from the onset of pain to the diagnosis of MM was 120 days. In 62.5 % of patients with kidney damage and pain, analgesics (mainly nonsteroidal anti-inflammatory drugs) were used before the diagnosis of MM. In patients with pain syndrome, compared with patients without it, at the onset of MM, pathological fractures (p = 0.01), bone plasmacytomas (p = 0.0001), hypercalcemia (p = 0.03) were significantly more often detected, and stage III was diagnosed according to Durie– Salmon (p = 0.021). The incidence of peripheral toxic polyneuropathy was 35 %. Complete regression of polyneuropathy symptoms was observed in 19 % of patients, and a significant decrease – in another 62 % of cases. The main manifestation of pain syndrome during auto-HSCT was pain in the oral cavity due to mucositis of varying severity.

Conclusion. Our study showed that MM patients mainly with stage III (86 % of cases) are referred for hospitalization to the National Medical Research Center for Hematology. Moreover, in 83 % of them the disease is accompanied by severe pain. More than a third of patients (35 %) developed bortezomib-induced peripheral polyneuropathy. Opioid analgesics are used for pain relief in the hospital, the indications for which were recorded in 45 % and 41 % of patients with MM during induction therapy and auto-HSCT, respectively.

Background. Assessing nutritional status at the start of treatment for patients with diffuse large B-cell lymphoma allows us to plan adequate accompanying treatment for patients in whom early nutritional support can improve the results of antitumor treatment.

Aim. To assess the prevalence of nutritional deficiency, features of usual diet energy and protein composition in patients with diffuse large B-cell lymphoma who are starting antitumor treatment.

Materials and methods. The study included 96 adult patients (m = 61), average age 38.9 ± 16.8 years, with newly diagnosed diffuse large B-cell lymphoma of various localization and prevalence. Additional laboratory screening (total protein, albumin, C-reactive protein (CRP), total cholesterol, triglycerides, daily urea excretion), anthropometric measurements (height, body weight (BW), weight loss over 6 months, body mass index), questionnaire (considering the intake of nutrients during the previous 3 days, calculating the intake of protein and energy, nitrogen balance) were performed in all patients before the first course of antitumor treatment. GLIM (Global Leadership Initiative on Malnutrition) criteria were used to diagnose protein-energy malnutrition (PEM).

Results. In studied patients, energy intake was 27.92 ± 6.47 kcal/kg BW per day, protein 0.91 ± 0.18 g/kg BW per day, and nitrogen balance was –3.57 ± 2.94 g/day. Moderate PEM was diagnosed in 37 (38.5 %) patients. Differences in some laboratory parameters were revealed in patients with PEM and without nutritional disorders: CRP level (20.38 ± 14.69 mg/L versus 12.52 ± 5.66 mg/L; p = 0.0004), glucose (5.07 ± 1.09 mmol/L versus 4.57 ± 0.62 mmol/L; p = 0.005), total cholesterol (4.35 ± 1.27 mmol/L versus 5.36 ± 1.45 mmol/L), triglycerides (1.22 ± 0.51 mmol/L versus 2.02 ± 0.78 mmol/L; p = 0.001).

Conclusion. Moderate PEM is detected in more than a third of patients with diffuse large B-cell lymphoma who begin antitumor treatment. The leading symptom in this case is unintentional weight loss over the past 6 months. An increased CRP level, moderate hyperglycemia, and lower concentrations of total cholesterol and blood triglycerides also characterize PEM in this cohort of patients. With sufficient energy supply, the amount of protein in the natural diet of patients with PEM turned out to be low, and the nitrogen balance was negative, which in the future can lead to the development of sarcopenia and requires nutritional support.

Background. Patients with lymphoproliferative disorders (LPD) are at increased risk of developing venous thromboembolic complications (VTEC). Existing risk assessment systems for VTEC (Khorana, Vienna, ThroLy, etc.) do not have sufficient prognostic accuracy in this patient population. The thrombodynamics test may improve the prognosis of VTEC and optimize the prophylactic use of anticoagulants in these patients.

Aim. To evaluate thrombodynamics test efficacy in assessing the risk of venous VTEC in LPD patients.

Materials and methods. Medical data of 990 patients with LPD who received treatment at the Kirov Research Institute of Hematology and Blood Transfusion from 2019 to 2021 were analyzed. Coagulation parameters were evaluated at admission, as well as the risk of developing VTEC by prognostic scales Khorana, Vienna, ThroLy, SAVED, and Padua. Data are presented as median and interquartile range. Mann–Whitney U test was used to compare two independent groups. Correlation was determined using Spearman’s rank correlation. Logistic regression was used to determine dependencies. The diagnostic value of laboratory tests was established through ROC analysis.

Results. In the overall cohort of LPD patients, the incidence of VTEC was 2.1 %. Screening coagulogram parameters in these patients did not exceed reference values. Patients with LPD who developed VTEC initially showed a significant increase in clot velocity (V), initial growth velocity (Vi), and clot size (Cs). It was found that the presence of spontaneous clots significantly increased the chances of developing a thrombotic event (odds ratio 3.99; 95 % confidence interval 1.56–10.22; p = 0.004). It was also determined that V velocity is an independent predictor of VTEC (adjusted odds ratio 1.053; 95 % confidence interval 1.016–1.090; p = 0.0046). The AUC determined by ROC analysis for the V parameter was 0.722 (threshold value 30.7 μm/min sensitivity 81 %, specificity 57.4 %).

Conclusion. Clot growth velocity is the most informative parameter of thrombodynamics test in predicting VTEC.