Фолликулярная лимфома (Фл) относится к индолентным зрелоклеточным В-клеточным лимфомам и, несмотря на рецидивирующее течение, в целом характеризуется благоприятным прогнозом с многолетней общей выживаемостью. Однако примерно в 20 % случаев заболевание имеет агрессивное течение с ранним прогрессированием и 5-летней общей выживаемостью всего 50 %, что свидетельствует о биологической неоднородности Фл. Ввиду крайне неблагоприятного прогноза случаи с прогрессированием заболевания в течение 2 лет от начала лечения представляют большую клиническую проблему. Какие прогностические модели риска ранней прогрессии Фл нам доступны и какие режимы 2-й и последующих линий противоопухолевой терапии использовать? Нужна ли высокодозная консолидация и когда? Выбор оптимальной терапии при ранней прогрессии Фл является сложной задачей и зависит как от варианта проведенного ранее лечения и статуса пациента, так и от объективно доступных терапевтических возможностей. В случае ранней прогрессии Фл после проведенной иммунохимиотерапии применяют альтернативный режим на основе ранее не использованного моноклонального антитела к СD20 (ритуксимаба или обинутузумаба) и химиопрепаратов неперекрестного действия. При СНОР-подобной индукционной терапии оптимальным препаратом 2-й линии является бендамустин. Кроме цитостатиков в комбинации с моноклональными антителами к СD20 в настоящее время в терапии Фл активно применяют новые агенты (иммуномодуляторы, ингибиторы сигнальных путей В-клеточного рецептора и гистонметилтрансферазы, BCL-2-ингибиторы и др.). В многочисленных клинических исследованиях продолжается активный поиск перспективных терапевтических опций для лечения Фл с тестированием новых лекарственных препаратов к другим В-клеточным мишеням и различными механизмами действия. В статье представлен клинический случай Фл с ранней генерализованной прогрессией, неэффективностью последующей интенсификации лечения с аутологичной трансплантацией гемопоэтических стволовых клеток и выбором терапии спасения в реалиях 2009-2012 гг.

Objective. Comparative evaluation of the effectiveness and toxicity profile of intensified chemotherapy regimens BEACOPP escalated (esc.), BEACOPP-14 and EACOPP‑14 in primary patients with classical Hodgkin’s lymphoma of an unfavorable prognostic group.Materials and methods. The study included 149 patients: 84 women (56 %) and 65 men (44 %) with a newly diagnosed classic Hodgkin’s lymphoma, who received antitumor treatment in the Department of high-dose chemotherapy with a bone marrow transplantation unit at the Р. A. Hertzen Moscow Oncology Research Institute from 2006 to 2018. The median age was 31 years (17–69). The majority of patients were diagnosed with Hodgkin’s lymphoma nodular sclerosis (88.6 %). All patients belonged to an unfavorable prognostic group, despite the fact that more than 1/3 of them had local stages of the disease. The most frequent adverse factors identified in the majority of patients were: massive lymph node lesion (bulky disease) – in 111 patients (74.5 %), B-symptoms – in 84 (56.4 %), increased erythrocyte sedimentation rate – in 55 (36.9 %), extranodal lesion – in 105 (70.5 %), including bones and bone marrow – in 10 (6.7 %) and 14 (9.4 %), respectively. Antitumor treatment was performed under the BEACOPP program in the following modifications: BEACOPP‑14 – 94 (63.1 %), EACOPP-14 – 32 (21.5 %), BEACOPP-esc. – 23 patients (15.4 %). Consolidating radiotherapy was performed in the majority of patients – 132 (88.6 %).Results. After the chemotherapy, remission of the disease was achieved in 141 patients (94.6 %), a complete response was in 101 of them (67.8 %). The immediate antitumor effect was more expressed when using the program BEACOPP‑14 (in 72.3 %), compared to EACOPP‑14 and BEACOPP-esc. (in 59.4 % and 60.9 %, respectively).Chemotherapy resistance was observed in 8 patients (5.4 %). Chemotherapy results were improved in combination with radiation therapy in 40 patients (26.8 %). After the end of chemoradiotherapy, complete remissions were achieved in more than 93.6 % of patients. Relapses occurred in 8 patients: early – in 3 (2.1 %) and late – in 5 (3.5 %). Four patients died (2.7 %): 1 – from disease progression, 2 – from resistant relapse, and 1 patient from other causes.With a median follow-up of 46 months, the 5-year overall survival rate was more than 93.7 %, event-free-more than 83 %, and relapse-free – 90.3 % or more. When evaluating long-term treatment results depending on the induction chemotherapy program, the outcome was better when using the BEACOPP-esc. in comparison with EACOPP‑14 and BEACOPP‑14. The most frequent myelotoxic complication – more than 90 % – on all chemotherapy programs was deep leukopenia. Thrombocytopenia III–IV degree developed more often on the BEACOPP-esc. (in 52.2 %), severe anemia – on EACOPP‑14 (in 44 %). Among infectious complications, mucositis prevailed and was most often observed on BEACOPP-esc. (in 74 %). Febrile neutropenia and herpetic infection developed less frequently, mainly in the BEACOPP-esc. and EACOPP‑14 program. Another serious complication was pneumonia, which was more frequently reported during BEACOPP‑14 (18.1 %). Secondary tumors, as a later complication, were less likely to be detected in the treatment program BEACOPP‑14 (1 %), compared to BEACOPP-esc. and EACOPP-14 (4.3 % and 3.1 %, respectively).Conclusion. All modifications of the BEACOPP program showed good direct effectiveness. However, the best long-term results, despite slightly more expressed toxicity, were noted on the BEACOPP-esc. program.

Classical Hodgkin's lymphoma is one of the most treatable lymphoproliferative diseases with current chemotherapy regimens. The 5-year overall survival rate among patients after initial chemotherapy reaches 95 %, however, despite the significant success achieved, the problem of refractoriness/relapse remains very relevant. A standard approach to the treatment of refractory/recurrent Hodgkin's lymphoma among young patients with preserved general status and chemoresponsive to salvage therapy tumor is high-dose consolidation chemotherapy followed by transplantation of autologous hematopoietic stem cells. The intensification of chemotherapy regimens is highly difficult task for a doctor during the COVID-19 pandemic, which requires careful assessment of a risk-benefit ratio.In current conditions, new targeted and immune drugs are used to overcome resistance and reduce toxicity among pretreated patients, which allows not only to improve the results of a treatment, but also to preserve the high quality of life among patients with extremely unfavorable prognosis.We show our experience of using a checkpoint inhibitor in combination with a dose-intensive regimen of DHAP (dexamethasone, cytarabine, cisplatin) in the treatment of a refractory classical Hodgkin's lymphoma followed by high-dose consolidation chemotherapy and allogeneic hematopoietic stem cells transplantation, among patients complicated with a new coronavirus infection in the post-transplant period.