Introduction. The risk of developing Hodgkin lymphoma (HL) with HIV infection is higher than in the general population, and the course of the disease itself is more aggressive. Currently, there is no unified approach to the treatment of HIV-related HL, and data on its epidemiology in the Russian Federation are limited.The objective was to study epidemiological characteristics, the used therapeutic tactics and the results of treatment for HIV-related HL.Methods and materials. The multicenter retrospective study included 46 patients with HIV- related HL treated in 9 centers of the Russian Federation. Descriptive statistics methods were used, the analysis of overall survival (OS) and progression-free survival (PFS) was performed using the Kaplan–Meier method.Results. HIV-related HL is more often represented by an advanced stage, B-symptoms, and extranodal lesions. The ABVD regimen was used as the first-line therapy in 60 % for HIV-related HL. The overall response to therapy was 81.6 %, and the 2-year OS and PFS were 85 % and 49 %, respectively. Factors that worsened OS were CD4+˂266 cells/mcL and general somatic status ECOG≥2.

Aim. To analyze the first experience of administering polatu-zumab vedotin combined with bendamustine and rituximab (Pola-BR) in clinical practice at some specialized institutions in the Russian Federation. Materials & Methods. The prospective multi-center study enrolled 39 patients with relapsed/refractory aggressive В-cell non-Hodgkin’s lymphomas (B-NHLs): 31 (79 %) patients with diffuse large B-cell lymphoma, 7 (18 %) patients with primary mediastinal (thymic) large B-cell lymphoma, and 1 (3 %) patient with gray zone lymphoma. There were 20 men and 19 women aged 19-69 years (median 43 years). All the patients were treated with Pola-BR protocol: bendamustine 90 mg/m2 on Days 1 and 2, rituximab 375 mg/m2 on Day 1, and polatuzumab vedotin 1.8 mg/kg on Day 1 of each 21-day cycle. Full treatment with 6 cycles was completed by 19 patients. PET-CT was performed prior to therapy and after the 2nd, 4th, and 6th Pola-BR cycles. The tumor response was evaluated according to the Lugano 2014 criteria. The toxicity profile was assessed by means of reporting adverse events according to the NCI CTCAE, version 5.0. Results. Objective response to the therapy, according to the Lugano 2014 criteria, was identified in 24 (61.5 %) patients: 19 (48.7 %) of them showed the complete response, and 5 (12.8 %) of them showed the partial one. Stable disease as best response to the therapy was reported in 3 (7.7 %) patients, disease progression was observed in 12 (30.8 %) patients. By the time of data analysis, the median follow-up duration was 16.8 months (range 5.3-24.2 months). The 2-year overall survival (OS) was 44 % (95% confidence interval [95% CI] 24-62 %), the median OS was 20.8 months. The 2-year progression-free survival (PFS) was 27 % (95% CI 12-43 %), the median PFS was 7.3 months. Adverse events of grade 3/4 included anemia (n = 4; 10.3 %), neutropenia (n = 15; 38.5 %), thrombocytopenia (n = 3; 7.7 %), and febrile neutropenia (n = 2; 5.1 %). In 2 patients with history of hepatitis B, the virus reactivation was identified on Pola-BR therapy. No cases of peripheral neuropathy were observed. Conclusion. Results obtained in real-world clinical practice correspond to the previously published data and demonstrate that polatuzumab vedotin therapy (Pola-BR protocol) has a controllable toxicity profile and is, therefore, a promising chemotherapy method of relapsed/refractory aggressive B-NHL treatment.

Background. Plasmablastic lymphoma (PBL) is a rare lympho-proliferative disease which is almost exclusively associated with immunodeficiency. Most ample experience of chemotherapy and hematopoietic stem cells transplantation (HSCT) in this lymphoma variant has been accumulated in HIV-positive patients. Aim. To describe the current approaches to PBL diagnosis and treatment in HIV-positive patients as well as to provide the results of the first multi-center retrospective study on PBL epidemiology and therapy efficacy in HIV-positive patients in the Russian Federation. Materials & Methods. The study included 26 HIV-positive patients with PBL who were treated and followed-up at 5 Russian centers during 2012-2019. The present study is a part of multi-center retrospective study on lymphoma epidemiology in HIV-positive patients in Russia. Results. PBL accounted for 9.5 % of all lymphomas in HIV-positive patients enrolled in multi-center retrospective study on lymphoma epidemiology in HIV-positive patients in Russia. Epidemiological characteristics of these patients corresponded to those described in previously published literature: the disease being diagnosed mainly at late stages (88 %), oral and nasal mucosa lesions with a common involvement of facial bones (65 %), and lack of optimal HIV-infection control (66.7 %). Most commonly, the patients received EPOCH-like treatment as first-line therapy (50 %). However, the efficacy of primary therapy appeared to be low. Overall survival (OS) and progression-free survival (PFS) during a year after first-line therapy onset was 57 % and 46 %, respectively. Bortezomib included in first-line therapy was associated with a trend to a more favorable prognosis. Half of patients showed a lymphoma relapse or progression after first-line therapy. Most used second-line regimen was DHAP. Overall response to second-line therapy was 38.5 %. After second-line therapy onset, 1-year OS and PFS were 26 % and 15 %, respectively. Conclusion. HIV-positive patients with PBL have poor prognosis. Efforts to improve the prognosis for HIV-positive patients with PBL should be aimed at increasing the efficacy of first-line therapy and should involve the use of intensive chemotherapy regimens with bortezomib. The role of auto-and allo-HSCTs in the treatment of PBL has not been clearly determined, however, PBL patients, despite their HIV-infec-tion, should be regarded as auto-HSCT-eligible in the first remission and allo-HSCT-eligible in case of relapse. Further prospective multi-center studies are needed to optimize the treatment of HIV-positive patients with PBL.

Introduction.The biological heterogeneity of chronic lymphocytic leukemia (CLL) is reflected in the rate of progression, the need for therapy, and the response to treatment. Analysis of prognostic factors contributes to improving the quality of treatment and rational distribution of healthcare resources.Materials and methods.Among 890 patients with documented stage of CLL, 405 (45.5 %) received treatment. As the first-line of treatment, 173 patients received intensive regimens (FCR or BR), 6 – new agents, and 226 – all other regimens. The initial stage of the disease, mutation status of IGHV, del17p with or without complex karyotype were analyzed as prognostic markers.Results.Immunochemotherapeutic regimens were shown to be highly effective in case planned amount of treatment was completed. The combination of such prognostic parameters as the initial stage of the disease, the mutation status of IGHV, and the presence of del17p and/or complex karyotype allows us to clearly identify a group of patients with an unfavorable prognosis, for which it is advisable to use either intensive programs or new agents in the first-line therapy.

Aim. The observational program was aimed at obtaining data on classical Hodgkin's lymphoma (cHL) incidence in the Russian Federation, therapy options, and clinical outcomes of treatment. The aim of the prospective part of the program was to standardize the approaches to therapy and to compare its outcomes with off-protocol treatment. Materials & Methods. The prospective-retrospective observational program for Hodgkin's lymphoma treatment engaged 32 regional and federal centers. It included 218 patients, 21 out of them were included into the prospective part of the RNWOHG-HD1 (Russian North-West Oncology and Hematology Group - Hodgkin Disease Study 1) program. The median age was 36 years (range 22-87 years). cHL stages I/II were identified in 48 % of patients, III/IV stages were reported in 52 % of patients. The prospective part of the program used escalating protocol in patients with stages I/IIA and without risk factors and de-escalating protocol in patients with advanced stages. Overall (OS) and progression-free (PFS) survivals were analyzed in 160 and 152 patients, respectively. PET-CT was used to assess the response in 33 % of patients. Results. The study used the following first-line chemotherapy regimens: ABVD in 42 %, BEACOPPst in 11 %, BEACOPP-14 in 17 %, BEACOPPesc in 25 %, and EACOPP in 1 % of cases. After the completion of first-line therapy objective response rate was 91 % including 61 % of complete responses. Response structure did not significantly differ in the groups of non-intensive therapy (ABVD and BEACOPPst), intensified regimens (BEACOPP-14, BEACOPPesc, and EACOPP), and treatment according to the RNWOHG-HD1 protocol (91 %, 92 %, and 96 %, respectively; p = 0.7226). In the total cohort the 3-year OS was 97 % (95% confidence interval [95% CI] 94-99 %), PFS was 87 % (95% CI 80-92 %). The 3-year PFS did not differ in ABVD, BEACOPPst, BEACOPP-14, BEACOP-Pesc, and RNWOHG-HD1 recipients (р = 0.37). International Prognostic Score (IPS) yielded significant results in PFS prediction for patients with IPS score of 5-6, but not for those with IPS score of 1-4 (p = 0.0028). Conclusion. The observational program showed that the majority of participating centers use the risk-adapted ABVD/ BEACOPPesc approach which explains no difference in PFS being found with the use of these chemotherapy options. The study demonstrated the need for PET-CT to assess the response since the CT alone cannot distinguish between complete and partial responses in a considerable number of patients. The prospective unified program for cHL treatment may well be implemented in the Russian Federation.

Aim. To assess prognostic factors and to analyze the outcomes of nivolumab therapy in patients with relapsed/re-fractory classic Hodgkin's lymphoma (cHL) after autologous hematopoietic stem cell transplantation (auto-HSCT). Materials & Methods. The retrospective analysis included 42 patients treated with nivolumab 3 mg/kg after auto-HSCT in the period from 2016 to 2020. The response to nivolumab therapy was assessed every three months by whole-body PET/CT based on LYRIC criteria. Toxicity profile was assessed by establishing adverse events (AE) based on NCI CTCAE 4.03 criteria. Results. The study included 42 patients with relapsed/re-fractory cHL: 21 (50 %) men and 21 (50 %) women. The median age was 32.5 years (range 22-43 years). At diagnosis the following cHL stages were identified: stage II in 14 pts (33.3 %), stage III in 12 pts (28.6 %), and stage IV in 16 pts (38.1 %). Primary chemoresistance after the first-line therapy was observed in 26 pts (61.9 %) and early relapse in 4 pts (9.52 %). The median follow-up was 38 months, 3-year overall survival was 97 % (95% confidence interval, 95% CI, 83.2-99.6 %), 3-year progression-free survival (PFS) was 34.8 % (95% CI 20.3-49.9 %; median 12.9 months). Objective response was reported in 69 % of patients, complete response (CR) in 33.3 %, partial response in 35.7 %, stable disease in 7.1 %, indeterminate response in 14.3 %, and progression in 9.5 % of patients. The analysis of factors affecting PFS revealed significant differences in patients who reached CR after 6 nivolumab cycles: 3-year PFS 56.2 % (95% CI 24.4-79.1 %) vs. 25.2 % (95% CI 10.46-43.1 %) in patients who did not reach CR (p = 0.054). If extranodal lesions were identified at nivolumab therapy onset, PFS was 29 % (95% CI 7.8-37.5 %) vs. 68 % (95% CI 35.9-86.8 %) in their absence (p = 0.0079). The overall rate of AEs on nivolumab therapy was 92.9 %, severe AEs of grade 3-4 were observed in 19.1 % of patients. Conclusion. Nivolumab shows high efficacy in the treatment of patients with relapsed/refractory cHL after the failure of auto-HSCT and considerably improves prognosis compared with historical control. The efficacy of nivolumab is independent of brentuximab vedotin use and duration of prior therapy. Throughout the follow-up period the toxicity level of nivolumab was acceptable and controlled. Clinical factors that affect prognosis for patients on immunotherapy were identified.

Проведение рандомизированных многоцентровых исследований в области трансплантации гемопоэтических стволовых клеток (ТГСК) представляет значительные трудности, поэтому доля таких исследований невелика. Большинство клинических рекомендаций основывается на данных популяционных многоцентровых исследований регистров или хорошо контролируемых проспективных одноцентровых нерандомизированных исследований. С целью определить критерии хорошо контролируемого одноцентрового исследования, результаты которого могут быть подтверждены в многоцентровом анализе, проанализировано 44 группы пациентов из 22 совместных с группой EBMT исследований. Проведено сравнение результатов этих исследований с одноцентровыми данными и спланированными исследованиями НИИ ДОГиТ им. Р.М. Горбачевой. Выявлено, что статистически значимые различия наблюдались в 43 % случаев, при этом вероятность расхождения результатов при повышении числа пациентов в одноцентровых группах не уменьшалась, а увеличивалась (отношение шансов 1,037; 95%-й доверительный интервал 1,001–1,074; p = 0,046), что свидетельствует о различиях в методологии одноцентровых и многоцентровых исследований. При анализе причин статистически значимых результатов сформулированы следующие необходимые критерии высококачественных одноцентровых исследований в области ТГСК: 1) режимы кондиционирования и профилактики реакции «трансплантат против хозяина» (если они не являются предметом исследования) должны соответствовать наиболее часто используемым в практике; 2) группы пациентов должны быть однородными по своему статусу; 3) в исследование не должны включаться пациенты, получавшие лечение более чем за 5 лет до анализа; 4) пациенты должны получать современную противоопухолевую терапию на до- и посттрансплантационном этапах; 5) каждая сравниваемая группа должна включать более 30–40 пациентов.

Цель. Оценка прогностических факторов и анализ результатов лечения при использовании ниволумаба у пациентов с рецидивами и рефрактерным течением классической лимфомы Ходжкина (кЛХ) после трансплантации аутологичных гемопоэтических стволовых клеток (аутоТГСК). Материалы и методы. Проведен ретроспективный анализ результатов лечения 42 пациентов, получавших ниволумаб в дозе 3 мг/кг после аутоТГСК в период с 2016 по 2020 г. Ответ на терапию ниволумабом оценивался каждые 3 мес. посредством ПЭТ/КТ всего тела согласно критериям LYRIC. Профиль токсичности оценивался путем регистрации нежелательных явлений (НЯ) согласно критериям NCI CTCAE 4.03. Результаты. В исследование включено 42 пациента с рецидивами и рефрактерным течением кЛХ: 21 (50 %) мужчина и 21 (50 %) женщина. Медиана возраста составила 32,5 года (диапазон 22–43 года). Стадия кЛХ на момент постановки диагноза: II — у 14 (33,3 %) пациентов, III — у 12 (28,6 %), IV — у 16 (38,1 %). Первичная химиорезистентность после первой линии терапии констатирована у 26 (61,9 %) пациентов, ранний рецидив — у 4 (9,52 %). Медиана наблюдения составила 38 мес., 3-летняя общая выживаемость — 97 % (95%-й доверительный интервал [95% ДИ] 83,2–99,6 %), 3-летняя выживаемость без прогрессирования (ВБП) — 34,8 % (95% ДИ 20,3–49,9 %; медиана 12,9 мес.). Объективный ответ констатирован у 69 % пациентов, полный ответ (ПО) — у 33,3 %, частичный — у 35,7 %, стабилизация заболевания — у 7,1 %, неопределенный ответ — у 14,3 %, прогрессирование — у 9,5 %. Анализ факторов, влияющих на ВБП, выявил статистически значимые различия у пациентов, достигших ПО после 6 введений ниволумаба: 3-летняя ВБП 56,2 (95% ДИ 24,4–79,1 %) vs 25,2 % (95% ДИ 10,46–43,1 %) у пациентов, не достигших ПО (p = 0,054). При наличии экстранодальных поражений на момент начала терапии ниволумабом ВБП составила 29 (95% ДИ 7,8–37,5 %) vs 68 % (95% ДИ 35,9–86,8 %) при их отсутствии (p = 0,0079). Общая частота НЯ на фоне терапии ниволумабом составила 92,9 %, тяжелые НЯ III–IV степени выявлены у 19,1 % пациентов. Заключение. Ниволумаб демонстрирует высокую эффективность в лечении пациентов с рецидивами и рефрактерным течением кЛХ после неудачи аутоТГСК и значительно улучшает прогноз по сравнению с историческим контролем. Эффективность ниволумаба не зависит от использования брентуксимаба ведотина или длительности предшествующей терапии. На протяжении всего периода наблюдения ниволумаб показал приемлемый и контролируемый уровень токсичности. Выявлены клинические факторы, влияющие на прогноз у пациентов на фоне иммунотерапии.

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region. Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model. Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months. Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones.

Background. The present paper discusses feasibility of first-and second-line therapies as well as the significance of different risk factors in the population of all patients with newly diagnosed Hodgkin's lymphomas (HL) in a 14-year period based on the data of Volgograd regional registry. Materials & Methods. During the period 2003 to 2017 the population registry of Department of Hematology of Volgograd Regional Clinical Oncology Dispensary included the data of all the patients with newly diagnosed HL (n = 622): 272 (44 %) men and 350 (56 %) women aged 18 to 84 years (mean age 38 years, median age 33 years). There were 97 (16 %) patients with early stages and without risk factors, 165 (27 %) patients with early stages and risk factors, 360 (59 %) patients with advanced stages, 308 (50 %) patients with toxic symptoms (stage B), and 179 (29 %) patients with bulky tumor lesions (> 10 cm). ABVD treatment regimen was administered in 190 (30.5 %) patients, in-creased-dose BEACO(D)PP in 39 (6 %) patients, BEACO(D) PP-14 in 159 (26 %) patients, standard BEACO(D)PP in 200 (32 %) patients, IVDG in 25 (4 %) patients, and other regimens in 9 (1.5 %) patients. The second-line treatment was administered in 120 (19 %) out of 622 patients. By the end of August 2018, the number of followed-up patients was 514 (83 %), 108 (17 %) patients had died. The prognostic value of the International Prognostic Score (IPS), PET, and other factors was assessed by means of Cox's multivariate regression analysis. Pharmacoeconomic analysis of differences between options of first-line therapy was based on Markov model. Results. In the group of patients with advanced HL stages treated with escalated BEACO(D)PP (the increased-dose regimen and BEACO(D)PP-14) 5- and 10-year overall survival (OS) was 83 % and 74 %, respectively, OS median was not reached. On standard BEACO(D)PP patients with advanced HL stages had OS median of 139 months (11.6 years) and 5-and 10-year OS of 68 % and 54 %, respectively (p = 0,012). In the group of patients with early stages and poor prognosis treated with escalated regimens BEACO(D)PP 5- and 10-year OS was 100 % and 90 %, respectively, in the combined group treated with ABVD and standard BEACO(D)PP it was 83 % and 75 % (p = 0.035). Replacement of procarbazine with dacarbazine in the standard and increased-dose BEACOPP regimens did not affect treatment efficacy. Markov analysis demonstrated the advantages of the escalated regimens for treatment of early stages with poor prognosis and advanced stages in terms of life years gained. Out of 7 IPS factors male sex, age > 45 years, hemoglobin < 105 g/L, and albumin < 40 mg/L significantly impacted OS. Based on these data an adjusted prognostic index was suggested. Conclusion. The advantage of the escalated strategy of first-line therapy in HL is reflected in survival parameters and is based on pharmacoeconomic evidence. The significance of some laboratory IPS risk factors can be reviewed; most obvious is increasing importance of PET for predicting the need for salvage therapy.

The costs of the first and subsequent therapy lines were analysed using a Markov model. Cost analysis of first-line therapy variants to be compared was based on cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). The analysis proved the cost-effectiveness of R-hyper-CVAD-R-HD-AraC program. Conclusion. R-hyper-CVAD-R-HD-AraC program meets eligibility criteria for effectiveness, toxicity and cost-effectiveness and can, therefore, be recommended as first-line therapy of mantle-cell lymphoma and be used for the further comparative clinical trials.