Высокодозная химиотерапия с трансплантацией аутологичных гемопоэтических стволовых клеток в первой линии терапии фолликулярной лимфомы

   Введение. При фолликулярной лимфоме (ФЛ) в большинстве случаев наблюдается высокая чувствительность опухоли к иммунохимиотерапии. Несмотря на продолжительную общую выживаемость (ОВ), течение заболевания характеризуется множественными рецидивами. Высокодозную химиотерапию (ВДХТ) с трансплантацией аутологичных гемопоэтических стволовых клеток (ауто-ТГСК) применяют при рецидиве ФЛ.

   Цель: оценить эффективность и безопасность ВДХТ с ауто-ТГСК в первой линии терапии ФЛ и выявить факторы риска прогрессии и рефрактерности заболевания.

   Материалы и методы. В проспективное одноцентровое исследование, проведенное с мая 2015 по январь 2023 г., включены 35 больных 18–65 лет (медиана 43 года) ФЛ 1–3 А градации t (14;18)+ с III–IV стадиями или II стадией с большим (> 6 см) размером опухоли. Проводили лечение по протоколу «ФЛ-2015»: 4 «R-CHOP», 2 «R-DHAP» и «BeEAM» с ауто-ТГСК. Статистический анализ (по намерению лечить) выполнен по состоянию данных на 12 января 2023 г.

   Результаты. У 86 % больных была IV стадия опухоли, у 79 % имелись 3–5 факторов Международного прогностического индекса ФЛ (Follicular Lymphoma International Prognostic Index, FLIPI). После окончания лечения частота общего ответа (ОО) и полной ремиссии (ПР) составили 90 и 90 %, частота прогрессии заболевания в течение 24 мес. (ПЗ24) — 3 %. После окончания индукции негативность по минимальной остаточной болезни (МОБ) была достигнута у 77 %. После полного завершения протокола МОБ-негативность достигнута у 96 % больных. Трехлетние ОВ, безрецидивная выживаемость, выживаемость без прогрессии и бессобытийная выживаемость составили 90, 90, 95 и 85 % (с одной и той же стандартной ошибкой в 9 %) при медиане наблюдения (оценка обратным методом Каплана — Мейера) 19 мес. (диапазон: от 1 до 91 мес.). Смертей из-за ранней токсичности в течение 100 дней после ауто-ТГСК не было. Прогностически неблагоприятными независимыми статистически значимыми (р < 0,01; критерий Вальда; отношение рисков > 1) предикторами прогрессии и рефрактерности по результатам многофакторного анализа по модели конкурирующих рисков Fine-Grey (р = 0,052 для модели) оказались: поражение костного мозга, высокий риск по ECOG, возраст больного > 50 лет, 4-я стадия заболевания, повышенная сывороточная концентрация лактатдегидрогеназы и В-симптомы.

   Заключение. Применение ВДХТ с ауто-ТГСК в первой линии у больных ФЛ эффективно и позволяет существенно снизить частоту ПЗ24 и ранней летальности.

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