Aim. To study the course of COVID-19 (COronaVIrus Disease 2019) in elderly patients with acute myeloid leukemia (AML), to analyze risk factors for unfavorable outcome.Materials and methods. The paper presents our own experience in the treatment of elderly (age ≥65 years) patients with AML and concomitant coronavirus infection in the hematology departments of City Clinical Hospital No. 52 (Moscow) from March 2020 to June 2022. The diagnosis of COVID-19 was considered confirmed based on a positive result of the polymerase chain reaction of an oropharyngeal and nasopharyngeal swab for SARS-CoV-2 and/or a typical radiological picture on a computed tomogram of the lungs.Results. An analysis of clinical, laboratory and instrumental data of 59 patients (30 (51 %) men, 29 (49 %) women) with AML and COVID-19 was carried out. All patients were treated for COVID-19 in accordance with the Temporary guidelines “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)” of the Russian Ministry of Health. Median age was 71 (65-91) years. AML was first verified in 27 % of hospitalized patients; 12 % were in remission of the disease. A month before hospitalization, 36 % of patients received antitumor therapy, and 19 % of patients had refractory AML. 17 % of hospitalized patients received antitumor therapy with cytarabine in small doses for vital indications. Death was recorded in 64 % of cases, in 24 % the cause of death was severe COVID-19. The unfavorable outcome was influenced by addition of secondary bacterial flora, refractory AML course and elderly age of patients.Conclusion. Pre-exposure prophylaxis with monoclonal antibodies and vaccination of patients may be the main methods of preventing infection and severe course of COVID-19.

Background. Acute myeloid leukemia (AML) is a highly aggressive oncological disease of the blood and bone marrow, requiring extremely toxic chemotherapy and massive supportive treatment to achieve stable remission. Currently, there is no work to provide medical care to these patients with a high risk of coronavirus infection. This paper presents treatment results of a large AML patient cohort during the COVID-19 pandemic.Aim. To assess the clinical features of coronavirus infection in AML patients.Materials and methods. A retrospective cohort study included patients hospitalized at City Clinical Hospital No. 52 (Moscow) between March 2020 and March 2022. Study inclusion criteria: 1) AML diagnosed within the last 3 years before the development of the COVID-19 pandemic; 2) age over 18 years; 3) laboratory confirmed SARS-CoV-2. AML status (newly diagnosed AML, relapse/refractory disease, remission), age, gender, comorbidity index, previous AML therapy and its outcomes were also assessed.Results. Among 218 patients with acute leukemia, 60 (27.5 %) patients had acute lymphoid leukemia, 158 (72.5 %) had AML. Patients with acute promyelocytic leukemia were allocated to a separate group - 20 (9 %) patients. The statistical data of the remaining 138 (63.5 %) patients with AML, their survival and mortality rates were assessed, and the main prognostic factors influencing the mortality and severity of coronavirus infection were identified. Also, our own results were compared with world statistics.Conclusion. Coronavirus infection in AML patients significantly worsens the prognosis. The main factors influencing the severity of coronavirus infection and survival and mortality rates are age, somatic status of patients due to the presence of concomitant chronic diseases, the development of deep hypoplasia of hematopoiesis, and the active AML status (disease onset or resistant course).

Background . In March 2020, oncohematologists faced the problem of severe COVID-19 coronavirus infection in patients after a high-dose chemotherapy and autologous or allogeneic bone marrow transplantation. This required a review of issues related to the selection of patients for blood stem cell transplantation (HSCT), the development of new preventive and therapeutic tactics aimed at treating infectious and immunological complications in patients of this category, depending on the nature and status of the underlying disease and the timing of treatment. Aim . To assess the severity, most typical complications and course of COVID-19 in patients during early and late posttransplant periods. Materials and methods . We analyzed the data of patients after HSCT with active coronavirus infection hospitalized in the hematology department from 2020 to 2021. A total of 25 patients were hospitalized: 4 after allogeneic transplantation, 21 after autologous transplantation. According to the timing of HSCT, patients were divided into 2 groups: early period (ETP) (2-90 days after HSCT) - 14 patients, late period (LTP) (3-24 months after HSCT) - 11 patients. Results . Severe coronavirus infection (grades III-IV according to computed tomography) was more often observed in patients in the ETP group (65 %) than in the LTP group (18 %). The incidence of respiratory failure was 70 and 36 % in the ETP and LTP groups, respectively. In the ETP group, agranulocytosis and the development of severe infectious complications (bacterial, fungal and viral) were observed significantly more often than in the LTP group, which required the appointment of reserve groups antibacterial therapy and antifungal therapy. Mortality in the ETP group was 35 %, while no deaths were recorded in the LTP group. The median duration of hospitalization for patients in the ETP and LTP groups was 20 and 13 days, respectively. Conclusion . Patients early after HSCT are at higher risk of developing lower respiratory tract infections, are more likely to require hospitalization in the intensive care unit, and have a greater risk of death from COVID-19. Therapy with genetically engineered biological drugs is not contraindicated in the case of leukopenia and agranulocytosis in this group of patients.

Diffuse large B-cell lymphoma is the most common immunomorphological variant of lymphoma in adults. Extranodal lesions are observed in a third of patients at the disease onset. The organs most often involved are the gastrointestinal tract, testicles, bones, thyroid gland, and skin. Primary involvement of the nasal cavity and paranasal sinuses occur extremely rarely and cause diagnostic and therapeutic difficulties.The article demonstrates a rare clinical case of newly diagnosed diffuse large B-cell lymphoma with sinonasal tract involvement. It took 6 months to verify the final diagnosis. At the moment, the induction stage of treatment for diffuse large B-cell lymphoma continues, the achieved complete metabolic response is maintained.

Background. The term diffuse large B-cell lymphoma (DLBCL) defines a heterogeneous group of lymphatic tumors. DLBCL is the most frequent immunomorphological variant among aggressive non-Hodgkin lymphomas (NHLs) in adults. It accounts for 30–40 % of all NHLs. Long-term results of treating newly diagnosed DLBCL have not been reliably evidenced in healthcare practice and, therefore, require further study. Aim. To assess the efficacy of chemotherapy for newly diagnosed DLBCL in terms of the 5-year progression-free survival (PFS) based on the analysis of data from the in-house hematology service registry at the Moscow City Clinical Hospital No. 52. Materials & Methods. The study enrolled 156 patients with newly diagnosed DLBCL in the period from 2015 to 2022. The patients were 35–85 years of age (median 65 years). Results. First-line R-CHOP/R-miniCHOP chemotherapy was administered to 70 % of patients, 28 % of patients received R-DA-EPOCH, and 2 % were treated either with R-B or R-CVP. Complete response was achieved in 100 (65 %) patients: 75 out of them (75 %) received R-CHOP/R-miniCHOP, whereas 25 (25 %) received R-DA-EPOCH. Induction mortality was below 2.5 %. The 5-year PFS was 32 % with the survival median of 20 months. As confirmed by the multivariate analysis, the age over 60 years (p = 0.003), high IPI risk group (p = 0.015), advanced stage of the disease (p = 0.002), and non-GCB subtype of tumor (p = 0.045) can be regarded as independent predictors of early DLBCL progression. Conclusion. DLBCL is an aggressive B-cell lymphoma and one of the most frequent immunomorphological NHL variants in the clinical practice of the Moscow City Clinical Hospital No. 52. Despite the use of generally accepted standard immunochemotherapy regimens, the results attained by the present study illustrate unresolved challenges in chemotherapy for newly diagnosed DLBCL patients. By now, more effective first-line DLBCL therapy methods already exist, which are confirmed by the results of clinical trials. As it is sometimes impossible to further escalate immunochemotherapy for obvious reasons (age restrictions, health status, co-morbidities, etc.), a new promising strategy appears to be the personalized chemotherapy based on the study of genetic DLBCL profile of each particular patient.

In December 2019, cases of severe respiratory infection were reported in Wuhan, China. The disease was caused by a new, previously undescribed coronavirus, structurally similar to the then known SARS-CoV virus. The World Health Organization has named the new virus SARS-CoV-2 and the disease it causes COVID-19. The problem of COVID-19 is exacerbated by the rapid spread of the SARS-CoV-2 virus and the development of life-threatening complications, the main of which is pneumonia. Due to the severity of the condition, from 5 to 10 % of patients are treated in intensive care units.SARS-CoV-2 initially attacks the respiratory system and causes symptoms such as fever, vomiting, headache, dizziness, general weakness, and diarrhea. Then these symptoms intensify in different directions, and the disease can often lead to death.Initially, only a few methods of symptomatic treatment were available and clinical trials of drugs that had previously shown their effectiveness against infection with the MERS-CoV and SARS-CoV viruses began. Temporary recommendations have appeared suggesting the use of some drugs both in monotherapy and in combination.In patients with hematologic malignancies, the immune response to the SARS-CoV-2 coronavirus is significantly reduced, which explains the high mortality rate (up to 38 %) of these patients hospitalized for SARS-CoV-2 infection. Recently, antiviral drugs and monoclonal antibodies have become available for pre- or post-exposure prophylaxis, as well as for early treatment of COVID-19. These treatments should be offered to patients at high risk of severe COVID-19 and to those who have not responded to vaccination. However, as changes in the genetic structure of the virus accumulate, some treatments may lose their clinical effectiveness against new variants.The combination of hematological malignancies and new coronavirus infection causes a more severe course of COVID-19 compared to the population and high mortality. Factors for an unfavorable prognosis for new coronavirus infection in patients with hematological malignancies include age over 60 years, a high comorbidity index, diagnoses such as acute leukemia, especially acute myeloid leukemia and myelodysplastic syndrome, disease status (relapse, progression, as well as newly diagnosed acute leukemia), severe COVID-19, agranulocytosis (myelotoxic or tumor).

Classical Hodgkin’s lymphoma (cHL) is a lymphoproliferative disease characterized by the presence of Hodgkin anderezovsky–Reed–Sternberg cells and a tumor microenvironment. Currently, much attention is paid to the microenvironment in cLH. A detailed understanding of the interaction between the tumor and its microenvironment opens up prospects for the cHL diagnosis and treatment. Innovative immunotherapeutic agents such as nivolumab make it possible to control and activate the immune response. Despite the high efficiency of standard protocols in young patients, therapy intensification is associated with organ toxicity and the development of secondary malignant neoplasms. At the same time, in elderly patients, the results of generally accepted antitumor treatment protocols should be considered suboptimal. In the last decade, the treatment of refractory cHL has improved significantly due to the use of immune checkpoint inhibitors.Taking into account the above, the priority issue in modern clinical hematology is to improve cHL treatment strategies not only in elderly but also in young patients by maintaining a balance between high efficacy and low toxicity. Moreover, the inclusion of nivolumab in first-line therapy is not only pathogenetically justified and effective, but also safe. The article presents data from clinical observations of the successful nivolumab use in combination with chemotherapy in patients with newly diagnosed cHL.

Patients with acute leukemia are one of the most vulnerable risk groups for infection with SARS-CoV-2 and severe course of coronavirus infection. During the first 2 years of the pandemic, the mortality rate of patients with acute leukemia was 11-48 %, depending on leukemia type, and only reached population levels in 2022. Risk factors for severe COVID-19 in patients with acute leukemia are old age, concomitant cardiac pathology, metabolic syndrome, and the absence of acute leukemia remission. Chemotherapy administered one month before hospitalization with COVID-19 diagnosis showed statistical significance in influencing hospital mortality only in the group of patients with acute myeloid leukemia. Despite this, the international medical community has recommended delaying the start of chemotherapy until clinical symptoms of coronavirus infection have completely resolved and a negative test result for SARS-CoV-2 has been obtained for all types of leukemia. Currently, the most optimal tactic is to prevent SARS-CoV-2 infection by vaccinating patients with acute leukemia receiving antitumor treatment. If the immunological response to vaccination is insufficient, it is possible to use virus-neutralizing monoclonal antibodies as a safe and effective method of primary prevention of COVID-19.

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. 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.

Background. Diffuse large B-cell lymphoma (DLBCL) is a potentially curable biologically heterogeneous lymphatic tumor. Standard R-CHOP therapy shows disappointing results, both immediate and longterm. To improve efficacy without additional toxicity, it is worth considering the possibility of using biologically oriented therapy.Aim. To evaluate the clinical efficacy and toxicity of the genotypedirected R-CHOP-X in patients with newly diagnosed DLBCL in real clinical practice.Materials and methods. A single-center prospective interventional clinical study included 30 patients with newly diagnosed DLBCL between September 2023 and September 2024. The median age was 60 (38–78) years. According to the international prognostic index, 23 (77 %) patients were classified as having a high risk of progression. Genotype incidence in the study cohort: MCD – 7 %, N1 – 20 %, BN2 – 7 %, EZB– 16 %, ST2 – 7 %, NOS – 43 %.Results. 30 patients received personalized genotype-directed therapy. Of these, 21 (70 %) patients completed treatment: the overall response rate was 100 % (complete metabolic response – 100 %). 9 (30 %) patients continue therapy: the overall response rate is 100 %. At 12 months, overall survival and progression-free survival were 100 % (95 % confidence interval 100 %). Hematological toxicity was assessed depending on the number of cycles (n = 144): grade III–I neutropenia was detected in 7 % of cycles, grade III–I anemia and grade III–I thrombocytopenia in 1.4 and 3.5 % of cycles, respectively. Non-hematological toxicity was generally grade ≤I–II.Conclusion. The results of this clinical trial are promising and provide preliminary evidence for the benefit of personalized genotype-directed antitumor therapy in newly diagnosed DLBCL. This therapeutic strategy demonstrates high clinical efficacy, particularly in the main target group – DLBCL with a high risk of progression with low toxicity. Further randomized studies are needed to confirm the effectiveness and implement the new approach in routine clinical practice.

Background. Coronavirus disease (COVID-19), caused by SARS-CoV-2, presents new challenges to hematologists, highlighting the vulnerability of patients with hematological malignancies, in particular with diffuse large B-cell lymphoma (DLBCL). Identification of hospital mortality risk factors is necessary for subsequent stratification of patients into risk groups, which will allow further risk-based therapy.Aim. To develop a prognostic model and identify risk factors for hospital mortality in patients with DLBCL associated with COVID-19.Materials and methods. The interim retrospective study included 112 patients with an immunohistochemically confirmed diagnosis of DLBCL, coronavirus infection verified based on polymerase chain reaction (PCR) for SARS-CoV-2, and viral pneumonia associated with COVID-19. To determine the risk factors for hospital mortality, a multivariate (logistic regression) statistical analysis was performed. The study end point was a binary variable - the patient vital status (discharged alive or died).Results and conclusion. Of the 112 patients, 24 died. Due to the limited number of patients compared to the number of predictors and to avoid overfitting, a two-stage approach to constructing a predictive model was used. In univariate analysis, statistically significant during hospitalization were the hematological disease status (complete remission/partial remission, progression/relapse, de novo), positive PCR result, C-reactive protein level >6 mg/L, platelets <100 thousand/pL, hemoglobin <120 g/L, albumin <35 g/L, lactate dehydrogenase >248 U/L, D-dimer >500 ng/mL and the degree of lung tissue damage according to computed tomography >50 % (grade II and above), respiratory failure I degrees and higher. The final model was constructed by minimizing the Akaike information criterion. The final model included a positive PCR result, stage II respiratory failure, hematologic disease status (relapse/progression), and albumin level at the time of hospital admission.

Treatment of immunocompromised patients with novel coronavirus infection (COVID-19) presents significant challenges. Currently, there are no unified approaches to the treatment of persistent COVID-19 in hematological malignancies. There is a need to develop recommendations for the management of such patients, chemotherapy protocols, as well as therapy for COVID-19 in case of SARS-CoV-2 virus persistence. Doctors are faced with cases of virus persistence, clinical manifestations during a long course of the infectious process and are not provided with methodological recommendations for patient supervision. As scientific data on the persistent COVID-19 course in patients with lymphoproliferative diseases accumulates, it is planned to create recommendations for the treatment of COVID-19 for patients in this group. This article describes a clinical case of persistent COVID-19 course in a comorbid patient with primary central nervous system large B-cell lymphoma during chemotherapy.

Background. At the end of 2019, a new coronavirus infection caused by the SARS-CoV-2 virus was registered. In March 2020, the first cases of COVID-19 were detected in Moscow. Patients with chronic lymphocytic leukemia, characterized by profound immune dysfunction, have risk factors for severe viral disease.Aim. To identify risk factors for hospital mortality and severe course of COVID-19, as well as to optimize therapeutic and preventive measures.Materials and methods. The analysis included 238 patients (142 (59 %) men and 96 (41 %) women) with chronic lymphocytic leukemia and COVID-19 with a median age of 66 (37-90) years, who were hospitalized at City Clinical Hospital No. 52 (Moscow) between April 2020 and April 2023. To compare hospital mortality and severity of COVID-19, patients were divided into 2 groups depending on the hospitalization period: 2020-2021 and 2022-2023, which correlates with the prevalence of some SARS-CoV-2 variants from December 2021 and changes in Moscow epidemiological situation.Results. Overall hospital mortality rate in 2020-2021 was 25 % (n = 45). Age over 73 years was a significant unfavorable factor in men. Cardiovascular diseases increase the risk of death by 2.3 times. Patients with a Charlson Comorbidity Index of 6 or more have a 2.2 times greater risk of death. A history of 1 or more lines of immunochemotherapy increased the risk of hospital mortality by 1.5 times. Relapse/progression of the disease were factors of unfavorable prognosis for patient survival. Binet stage C also showed a significant unfavorable prognosis. When studying all cases of death (n = 51), complications such as myelotoxic agranulocytosis, secondary bacterial complications and severe interstitial pulmonary damage >75 % were identified.Conclusion. Coronavirus infection caused by SARS-CoV-2 represents an infectious threat among patients with chronic lymphocytic leukemia and may affect the regimen and tactics of antitumor therapy. The use of a full range of preventive measures, vaccination and pre-exposure prophylaxis in this cohort of patients is of great importance.

This lecture is devoted to a common inherited hemorrhagic disorder, von Willebrand disease (vWD). The article presents the history of the discovery of vWD, the structure and function of von Willebrand factor (vWF), the classification of vWD and its main clinical manifestations. The central topic of the lecture is vWD in pregnant women. It is indicated that to date there are no proven guidelines for the treatment of women with vWD during pregnancy, childbirth, and in the postpartum period. Due to the risk of bleeding, the management of pregnant women with vWD, especially those with its severe form, should be performed by a multidisciplinary team including a hematologist, obstetrician-gynecologist, anesthesiologist, and neonatologist. In patients with type 1 vWD, pregnancy is often uncomplicated, but there is always the risk of bleeding. Type 2 vWD (qualitative variants) requires continuous monitoring. In type 3 vWD, the most clinically severe variant, continuous monitoring of patients is also necessary, with initiation of replacement therapy (factor VIII and vWF) until the end of pregnancy. Conclusion. Von Willebrand disease is a heterogeneous disorder with a highly variable clinical presentation. It carries a high risk of prenatal and postpartum hemorrhage, therefore vWD patients are more likely to require blood transfusion. Since the sample of patients with vWD is quite small, further observations and studies are needed to obtain more reliable results. Key words: von Willebrand disease, von Willebrand factor, classification, clinical picture, diagnosis during pregnancy, management of pregnancy and childbirth

Background. In March 2020, doctors faced the problem of severe COVID-19 coronavirus infection in patients with multiple myeloma. This required a review of issues related to the selection of patients, the development of new preventive and therapeutic tactics aimed at treating infectious and immunological complications in patients of this category, depending on the nature and status of the underlying disease and the timing of treatment.Aim. To assess the severity of multiple myeloma, the most common complications and features of the COVID-19 course in patients with multiple myeloma at different therapy stages (disease onset, remission, maintenance therapy, progression/refractory disease).Materials and methods. From March 2020 to May 2022, 89 patients diagnosed with multiple myeloma and coronavirus infection caused by the SARS-CoV-2 virus were hospitalized at City Clinical Hospital No. 52 (Moscow). After assessing the severity, a decision was made on patient management, and if necessary, according to indications, the patient received specific antitumor therapy for multiple myeloma and treatment of coronavirus infection simultaneously.Results. Treatment for coronavirus infection was carried out in accordance with the clinical recommendations of the Russian Ministry of Health at that time. It included antiviral, anticoagulant therapy, transfusions of fresh frozen convalescent plasma with a high titer of antibodies, genetically engineered biological drugs and monoclonal antibodies; if necessary, patients received antibacterial and antifungal, hormonal therapy. Specific chemotherapy was also administered according to indications.Conclusion. Patients with multiple myeloma are at higher risk of severe COVID-19 infection. Today, the problem of developing adequate therapeutic tactics for managing patients with multiple myeloma and coronavirus infection still remains relevant. It is necessary to develop an optimal protocol for the management of such patients, including an assessment of prognostic factors, identification of clearly defined indications and contraindications for chemotherapy, and a description of supportive therapy.

Диффузная крупноклеточная В-клеточная лимфома (ДВКЛ) представляет собой крайне гетерогенное опухолевое заболевание лимфоидной природы и является наиболее распространенным иммуноморфологическим вариантом из группы агрессивных неходжкинских лимфом (НХЛ). Треть ДВКЛ характеризуется первичной экстранодальной локализацией и вариабельным прогнозом в зависимости от зоны поражения. Следует отметить, что именно молекулярные характеристики играют ключевую роль в различиях клинических проявлений, прогнозе опухолевого заболевания и совершенствовании терапевтического подхода с включением новых противоопухолевых агентов. Экстранодальная ДВКЛ молочной железы, кожи, матки, иммунопривелигированных зон, таких как центральная нервная система (ЦНС), и яичка, обладает фенотипом В-клеток постгерминального уровня (non-GCB) и высокой частотой мутаций MYD88/CD79B. В свою очередь для экстранодальной ДВКЛ желудка и щитовидной железы характерно благоприятное течение заболевания с низкой частотой выявляемости non-GCB-фенотипа. Ритуксимаб-содержащая иммунохимиотерапия (ИХТ) служит стандартом не только для нодальных форм заболевания, но и при первичной экстранодальной локализации. В настоящее время оптимизация стратегии терапии в соответствии с клинико-иммуноморфологическими характеристиками и молекулярной гетерогенностью является крайне актуальной проблемой. В данном обзоре рассматриваются ключевые сигнальные пути и новые подходы к противоопухолевой терапии первичной экстранодальной ДВКЛ. Diffuse large B-cell lymphoma (DLBCL) is an extremely heterogeneous tumour disease of lymphoid nature and is the most common immunomorphological variant from the group of aggressive non-Hodgkin’s lymphomas (NHL). One third of DLBCL is characterised by primary extranodal localization and a variable prognosis depending on the area of the lesion. It should be noted that it is molecular characteristics that play a key role in the differences in clinical manifestations, prognosis of tumour disease and improvement of the therapeutic approach with the inclusion of new antitumour agents. Extranodal DLBCL of the breast, skin, uterus, immunoprivileged areas such as the central nervous system (CNS) and testis have a postgerminal B-cell (non-GCB) phenotype and a high frequency of MYD88/CD79B mutations. In turn, extranodal gastric and thyroid DLBCL is characterised by a favourable disease course with a low incidence of the non-GCB phenotype. Rituximab- containing immunochemotherapy (ICT) is the standard not only for nodal forms of the disease, but also for primary extranodal localisation. Currently, optimizing the therapy strategy according to clinical and immunomorphological characteristics and molecular heterogeneity is a highly relevant problem. In this review, key signalling pathways and new approaches to antitumour therapy of primary extranodal DLBCL are discussed.

Коронавирусная инфекция (COVID-19) – это острое респираторное заболевание, вызванное вирусом SARS-CoV-2, впервые было отмечено в городе Ухань (Китай) и быстро распространилось по всему миру. В условиях пандемии COVID-19 проведение специфического противоопухолевого лечения у пациентов с агрессивными В-клеточными лимфомами стало одной из сложных задач. Проведение специфической противоопухолевой терапии пациентов с гемобластозами, в том числе с агрессивными лимфопролиферативными заболеваниями, требует безотлагательного начала. Отсрочка специфической терапии может привести к прогрессированию лимфомы. Выбирая протокол химиотерапевтического режима, необходимо учитывать риск реактивации COVID-19 на фоне миелотоксической аплазии костномозгового кроветворения, а также дополнительного присоединения бактериальной и грибковой инфекции. Подтвержденная коронавирусная инфекция не должна быть противопоказанием к химиотерапии. В данной публикации представлены собственное клиническое наблюдение течения COVID-19 у пациента с первичной медиастинальной В-клеточной лимфомой на этапе химиотерапевтического лечения, а также выбор режима противоопухолевой терапии. Coronavirus disease (COVID-19) is an acute respiratory disease caused by the SARS-CoV-2 virus, was discovered first in Wuhan (China) and quickly spread throughout the world. Specific antitumor treatment in patients with aggressive B-cell lymphomas has become one of the most challenging issues in the context of the COVID-19 pandemic. An immediate start of specific antitumor therapy for patients with hematological malignancies including aggressive lymphoproliferative diseases (LPD) is required. The delay of specific therapy may lead to progression of lymphoma. It is necessary to consider the risk of reactivation of COVID-19 due to myelotoxic aplasia of bone marrow hematopoiesis, as well as further development of bacterial and fungal infections when choosing a chemotherapy regimen protocol. Confirmed COVID-19 infection should not be a contraindication for chemotherapy. This publication presents our own clinical experience of COVID-19 infection case in a patient with primary mediastinal B-cell lymphoma at chemotherapy treatment stage, as well as the choice of tactics for the antitumor therapy regimen.

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Coronavirus infections (COVID-19) caused by SARS-CoV-2 present new challenges to hematologists, emphasizing the vulnerability of patients with hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL). Aims: Identification of clinical and paraclinical predictors of in-hospital case fatality in patients with DLBCL associated with COVID-19. Methods: Between April 21, 2020, and December 31, 2022, 103 patients with DLBCL (52 men, 51 women) remained under observation by the hematology service of the municipal clinical hospital #52 (Moscow). A multivariable logistic regression analysis was performed to identify predictors of in-hospital case fatality. The binary endpoint of vital status (discharged alive vs death) was used. Statistical significance level of 0.05 was applied. Results: The retrospective analysis included 103 patients, among whom 24 had adverse outcome. Independent variables at the time of hospitalization included sex, age, status of the hematologic condition (remission, progression/relapse, stabilization, de novo diagnosed DLBCL), Charlson comorbidity index, clinical manifestations (fatigue, subfebrile and febrile temperature, cough, dyspnea, diarrhea syndrome), polymerase chain reaction (PCR), COVID-associated immunoglobulins, blood count (lymphocytes, WBC, platelets, hemoglobin), C-reactive protein (CRP), D-dimer, immunoglobulins M and G, albumin, lactate dehydrogenase (LDH), chemotherapy within the month prior to COVID-19 manifestation, exposure to anti-CD20 monoclonal antibodies within the previous 12 months (anti-CD20 mAb), severity of lung damage according to computerized tomography (CT), respiratory failure and chemotherapy line (first, second and subsequent). As the number of included patients was limited, compared to the number of predictors, and to prevent overfitting, a two-step approach was applied to a predictive model. At the first step univariable logistic regression was used to identify variables statistically significantly associated with the outcome, with significance threshold set at p<0.05. The univariable analysis demonstrated statistical significance of the following variables for the hospitalization period: status of the hematologic condition (relapse/progression), PCR positivity, CRP above 6 mg/L, platelets below 100.000 cells/μL, hemoglobin below 120 g/L, albumin below 35 g/L, LDH above 248 U/L, D-dimer above 500 ng/mL, CT lung damage above 50% (CT grade 2 or higher) and grade 2 respiratory failure. Subsequently, the final model was created by minimizing the Akaike information criterion. PCR positivity, CT grade 2, respiratory failure grade 2, hemoglobin, albumin and LDH levels on admission were included in the final model. The area under the ROC curve for the model was 0.959 (95%CI: 0.916;1) (see Figure 1), which is equivalent to a very high quality of outcome prediction. Figure 1.Summary/Conclusion: The suggested predictive model should be used as an additional tool predicting the risk of in-hospital case fatality in patients with DLBCL who develop coronavirus infection caused by SARS-CoV-2. Keywords: B cell lymphoma, COVID-19