Efficacy of donor lymphocyte infusion in patients after different types of allogeneic hematopoietic stem cell transplantation

Abstract

AIM: To evaluate the efficacy of donor lymphocyte infusion (DLI) to prevent and treat recurrences in patients after different types of allogeneic hematopoietic stem cell transplantation (allo-HSCT)/MATERIAL AND METHODS: Data from 118 patients with malignant blood diseases were analyzed. Allo-HSCTs from HLA-matched related donors (n=49), HLA-matched unrelated donors (n=50), partially HLA-matched unrelated donors (n=2), and haploidentical donors (n=24) were performed. The indications for DLI were underlying disease relapse (59 DLIs), resistant disease course (n=40), minimal residual disease (n=16), falling donor chimerism (n=15), and recurrence prevention (n=13)/RESULTS: Therapy response was obtained after 57 (44%) DLIs. There were 36 (25%) and 30 (21%) cases of acute and chronic graft-versus-host reactions (GVHR), respectively. The use of DLI from HLA-matched donors, its performance in the periods of D+100 to one year after allo-HSCT, a donor chimerism level of over 90% at the moment of DLI, the administration of the initial DLI dose of below 1·106 CD3+/kg, and the development of chronic GVHR after DLI were associated with the highest rate of therapy responses. The overall survival rates of patients with DLI were significantly influenced by factors, such as DLI periods, donor chimerism levels at DLI, and the development of chronic GVHR after DLI/CONCLUSION: The choice of the optimal dose of cells, the periods of DLI and its preventive administration improve prognosis in patients after allo-HSCT. The occurrence of acute GVHR is affected by the degree of HLA matching and the type of a donor. The development of chronic GVHR after DLI is associated with the highest rate of responses to DLI and higher survival rates.

Full Text

Эффективность инфузии донорских лимфоцитов у пациентов после различных видов аллогенной трансплантации гемопоэтических стволовых клеток. - Резюме. Цель исследования. Оценить эффективность инфузии донорских лимфоцитов (ИДЛ) с целью профилактики и лечения рецидивов у пациентов после различных видов аллогенной трансплантации гемопоэтических стволовых клеток (алло-ТГСК). Материалы и методы. Проанализированы данные 118 пациентов со злокачественными заболеваниями системы крови. Алло-ТГСК от совместимого по системе HLA родственного донора выполнены у 49, от совместимого неродственного - у 50, от частично совместимого неродственного - у 2, от гаплоидентичного донора - у 24 пациентов. Показаниями к ИДЛ были рецидив основного заболевания (59 ИДЛ), резистентное течение (40 ИДЛ), "минимальная остаточная болезнь" (16 ИДЛ), снижение донорского "химеризма" (15 ИДЛ) и профилактика рецидива (13 ИДЛ). Результаты. Ответ на терапию достигнут после 57 (44%) ИДЛ. Число случаев развития острой реакции трансплантат против хозяина (РТПХ) после ИДЛ составило 36 (25%), хронической РТПХ - 30 (21%). Использование ИДЛ от совместимого по системе HLA донора, проведение ИДЛ в сроки от Д+100 до 1 года после алло-ТГСК, уровень донорского "химеризма" на момент ИДЛ более 90%, использование начальной дозы ИДЛ менее 1·106 CD3+/кг, а также развитие хронической РТПХ после ИДЛ были ассоциированы с наибольшей частотой ответов на терапию. На уровни общей выживаемости ОВ пациентов с ИДЛ достоверно влияли такие факторы, как сроки проведения ИДЛ, уровень донорского "химеризма" на момент ИДЛ, а также развитие хронической РТПХ после ИДЛ. Заключение. Выбор оптимальной клеточной дозы, сроков проведения ИДЛ, а также проведение ИДЛ с превентивной и профилактической целью улучшают прогноз у пациентов после алло-ТГСК. На возникновение острой РТПХ после ИДЛ влияют степень совместимости по системе HLA и тип донора. Развитие хронической РТПХ после ИДЛ ассоциировано с наибольшей частотой ответов на ИДЛ и более высокой общей выживаемостью.
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Copyright (c) 2013 Slesarchuk O.A., Babenko E.V., Semenova E.V., Bondarenko S.N., Éstrina M.A., Morozova E.V., Paina O.V., Vavilov V.N., Smirnov B.I., Zubarovskaia L.S., Afanas'ev B.V.

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