Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children24010.24287/1726-1708-2019-18-2-11-21PROMISING STUDIESПЕРСПЕКТИВНЫЕ ИССЛЕДОВАНИЯαβ-T-cell-depleted haploidentical hematopoietic stem cell transplantation in children with chemorefractory acute myeloid leukemiaАллогенная трансплантация гемопоэтических стволовых клеток от гаплоидентичного донора с TCR αβ-деплецией у детей с химиорезистентным острым миелобластным лейкозомhttps://orcid.org/0000-0003-0520-5630ShelikhovaL. N.ШелиховаЛ. Н.
Russian Federation

Larisa N. Shelikhova, MD, hematologist, head.

117997, Moscow, Samory Mashela st., 1.

Шелихова Л.Н., врач-гематолог, заведующая отделением трансплантации гемопоэтических стволовых клеток № 1.

117997, Москва, ГСП-7, ул. Саморы Машела, 1.

lnik1975@mail.ruhttps://orcid.org/0000-0001-7652-7704IlushinaM. A.ИлюшинаМ. А.
Russian Federation
https://orcid.org/0000-0001-8148-6310SemiglazovaK. V.СемиглазоваК. В.
Russian Federation
https://orcid.org/0000-0002-9912-6572ShekhovtsovaZh. B.ШеховцоваЖ. Б.
Russian Federation
https://orcid.org/0000-0002-5641-8567ShashelevaD. A.ШашелеваД. А.
Russian Federation
https://orcid.org/0000-0001-5618-7159KhismatullinaR. D.ХисматуллинаР. Д.
Russian Federation
https://orcid.org/0000-0003-4767-5382KurnikovaE. E.КурниковаЕ. Е.
Russian Federation
PershinD. S.ПершинД. С.
Russian Federation
https://orcid.org/0000-0003-2689-0569BalashovD. N.БалашовД. Н.
Russian Federation
https://orcid.org/0000-0002-7696-1153RadyginaS. A.РадыгинаС. А.
Russian Federation
https://orcid.org/0000-0002-0231-1617TrakhtmanP. E.ТрахтманП. Е.
Russian Federation
https://orcid.org/0000-0002-0813-5626KalininaI. I.КалининаИ. И.
Russian Federation
https://orcid.org/0000-0003-3513-8299MuzalevskiiY. O.МузалевскийЯ. О.
Russian Federation
https://orcid.org/0000-0003-0497-9175KazachenokA. S.КазаченокА. С.
Russian Federation
https://orcid.org/0000-0001-5949-5317ZaharovaV. V.ЗахароваВ. В.
Russian Federation
https://orcid.org/0000-0003-0079-7761BrilliantovaV. V.БриллиантоваВ. В.
Russian Federation
https://orcid.org/0000-0002-2352-7716OlshanskayaYu. V.ОльшанскаяЮ. В.
Russian Federation
https://orcid.org/0000-0002-8580-3499PanferovaA. V.ПанфероваА. В.
Russian Federation
https://orcid.org/0000-0001-9634-5828ZerkalenkovaE. A.ЗеркаленковаЕ. А.
Russian Federation
https://orcid.org/0000-0001-7130-8596BaidildinaD. D.БайдильдинаД. Д.
Russian Federation
https://orcid.org/0000-0002-2322-5734NovichkovaG. A.НовичковаГ. А.
Russian Federation
https://orcid.org/0000-0002-1643-5960RumyantsevA. G.РумянцевА. Г.
Russian Federation
https://orcid.org/0000-0002-0016-6698MaschaA. A.МасчанА. А.
Russian Federation
https://orcid.org/0000-0003-1735-0093MaschanM. A.МасчанМ. А.
Russian Federation
Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России2906201918211212806201928062019Copyright ©; 2019, «D. Rogachev NMRCPHOI»Copyright ©; 2019, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2019«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/240

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.

Терапия первично-рефрактерных форм острого миелоидного лейкоза (ОМЛ) и рефрактерных рецидивов по-прежнему сложная, не решенная задача в детской онкогематологии. Аллогенная трансплантация гемопоэтических стволовых клеток (алло-ТГСК) – единственный излечивающий метод терапии химиорезистентных форм. В данной работе представлены результаты алло-ТГСК от гаплоидентичного донора с TCR αβ-деплецией у детей с химиорезистентным ОМЛ. В исследование были включены 36 пациентов с первично-рефрактерным (n = 14) и рефрактерным (n = 22) рецидивами, получившие трансплантацию на базе НМИЦ ДГОИ им. Дмитрия Рогачева Минздрава России; медиана наблюдения – 2,2 года. Предтрансплантационный режим терапии включал циторедукции с цитарабином и флударабином с последующим треосульфан-содержащим режимом кондиционирования с добавлением мелфалана либо тиофосфамида. Антитимоцитарный глобулин получили 14 пациентов; тоцилизумаб +/- абатацепт – 12; αβ-T- и CD19-деплеция трансплантата проведена с помощью аппаратов CliniMACS Plus или CliniMACS Prodigy. Посттрансплантационная терапия включала инфузию модифицированных донорских лимфоцитов с применением или без применения гипометилирующих препаратов. У 30 (83%) пациентов клинико-гематологическая ремиссия достигнута на +30-е сут. Кумулятивная вероятность развития острой РТПХ II–IV степени – 25%; хронической РТПХ – 18%; трансплантационная смертность – 6%; прогрессия или рецидив заболевания – 48%. Двухлетняя бессобытийная и общая выживаемость – 46 и 41% соответственно. Восстановление NK-клеток на +30-е сут выше медианы ассоциировано со статистически значимым улучшением выживаемости. Таким образом, алло-ТГСК от гаплоидентичного донора с αβT-деплецией может быть куративной опцией у 45% детей с химиорезистентым ОМЛ и ассоциирована с низкой трансплантационной летальностью и вероятностью развития РТПХ. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ.

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