Abstract
Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology. Children with AML who fail to achieve complete remission on high-dose cytarabine and antracyclines have no chance for survival without allogeneic hematopoietic stem cell transplantation. We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Thirty-six patients with either primary refractory (n = 14) or relapsed refractory (n = 22) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent treatment with treosulfan and either melphalan or thiophosphamide. Serotherapy consisted of antithymocyte globuline in 14 pts and targeted immunomodulation with tocilizumab +/- abatacept in 22 pts. Grafts were PBSCs engineered by TCR-αβ/CD19 depletion. Posttransplant preemptive therapy included modified donor lymphocyte infusions with or without hypomethylating agents. Complete remission was achieved in 30 (83%) рts. The cumulative incidence of acute GVHD grade II–IV was 25%, and the cumulative incidence of chronic GVHD was 18%. Transplant-related mortality was 6%, and relapse incidence was 48%. Event-free survival was 46%, and overall survival was 41% at 2 years. Good early recovery of NK cells was associated with significantly improved survival and decreased relapse incidence. Our data suggest that αβ-T-cell-depleted haploidentical HSCT provides a reasonable chance of cure in a cohort of children with chemorefractory acute myeloid leukemia and creates a solid basis for further improvement. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.
Highlights
Терапия первично-рефрактерных форм острого миелоидного лейкоза (ОМЛ) и рефрактерных рецидивов по-прежнему сложная, не решенная задача в детской онкогематологии
Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology
We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia
Summary
С июня 2012 по сентябрь 2017 года на базе отделений ТГСК НМИЦ ДГОИ им. Дмитрия Рогачева Мин- здрава России 36 пациентам (19 девочек и 17 мальчиков) с химиорезистентным ОМЛ была проведена алло-ТГСК. Медиана возраста пациентов на момент ТГСК составила 9,6 (от 1 до 18) года; медиана наблюдения для выживших пациентов – 2,2 года. Для пациентов с первично-рефрактерными формами приятного прогноза; 7 – промежуточного и 3 – бла-. ОМЛ медиана времени от момента постановки ди- гоприятного прогноза в соответствии с международагноза до трансплантации составила 123 224) дня; при рецидивах ОМЛ: от момента установ- выявленных цитогенетических перестроек методом ления диагноза до момента рецидива – 11,3 (от 3,7 секвенирования нового поколения (NGS) в 6 случаях до 23) мес.; время от рецидива до трансплантации – зафиксированы множественные клональные моле-. Все но-биологических исследований были доступны у пациенты получили первую линию терапии в соот-
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