Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children73510.24287/1726-1708-2023-22-3-14-27ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИThe results of therapy with venetoclax, daratumumab and plerixafor as part of the conditioning regimen in chemotherapy-refractory acute leukemia in childrenРезультаты применения венетоклакса, даратумумаба и плериксафора в составе кондиционирования при химиорефрактерных формах острых лейкозов у детейhttps://orcid.org/0000-0003-1216-817XKlimentovaM. A.КлиментоваМ. А.
Russian Federation

Moscow

Москва

klimentowa1702@mail.ruhttps://orcid.org/0000-0003-0520-5630ShelikhovaL. N.ШелиховаЛ. Н.
Russian Federation

Moscow

Москва

lnik1976@mail.ruhttps://orcid.org/0000-0001-7652-7704IlushinaM. A.ИлюшинаМ. А.
Russian Federation

Moscow

Москва

mariya.ilyushina@fccho-moscow.ruhttps://orcid.org/0000-0001-8754-1376BlagovS. L.БлаговС. Л.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0002-7387-9197PerminovaM. E.ПерминоваМ. Е.
Russian Federation

Moscow

Москва

margaritaperm92@gmail.comhttps://orcid.org/0000-0002-0889-6986PopovА. M.ПоповА. М.
Russian Federation

Moscow

Москва

uralcytometry@gmail.comhttps://orcid.org/0000-0002-5220-7412KashporS. A.КашпорС. А.
Russian Federation

Moscow

Москва

svetlana.kashpor@fccho-moscow.ruFadeevaM. S.ФадееваМ. С.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2352-7716OlshanskayaYu. V.ОльшанскаяЮ. В.
Russian Federation

Moscow

Москва

Yuliya.olshanskaya@fccho-moscow.ruhttps://orcid.org/0000-0002-6607-1384GlushkovaS. Yu.ГлушковаС. Ю.
Russian Federation

Moscow

Москва

rizoiu.svetlana@gmail.comhttps://orcid.org/0000-0002-6148-7209PershinD. E.ПершинД. Е.
Russian Federation

Moscow

Москва

dimprsh@icloud.comhttps://orcid.org/0000-0003-2689-0569BalashovD. N.БалашовД. Н.
Russian Federation

Moscow

Москва

bala8@yandex.ruhttps://orcid.org/0000-0002-0016-6698MaschanА. А.МасчанА. А.
Russian Federation

Moscow

Москва

amaschan@mail.ruhttps://orcid.org/0000-0003-1735-0093MaschanM. A.МасчанМ. А.
Russian Federation

Michael A. Maschan Dr. Med. Sci., Professor, Deputy Director General, Director of the Institute of Molecular and Experimental Medicine.

1 Samory Mashela St., Moscow 117997

Масчан Михаил Александрович доктор медицинских наук, профессор, заместитель генерального директора – директор Института молекулярной и экспериментальной медицины.

117997, Москва, ул. Саморы Машела, 1

mmaschan@yandex.ruThe Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России0310202322314270606202303072023Copyright ©; 2023, «D. Rogachev NMRCPHOI»Copyright ©; 2023, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2023«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/735

The main outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in chemotherapy-refractory acute leukemia remain suboptimal due to a high relapse rate. The incorporation of targeted anti-leukemia agents into the conditioning regimens is a potential approach to improve the efficacy of HSCT. We assessed the safety and potential efficacy of the addition of venetoclax, daratumumab, and plerixafor to the conditioning regimens in children with chemotherapy-refractory acute leukemias who received allogeneic TCRab/CD19-depleted HSCT. We used data from a pilot study, as well as the data of patients from a retrospective cohort who received similar therapy according to the individual indications. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All 43 patients (33 acute myeloid leukemias (AML), 8 T-cell acute lymphoblastic leukemias (T-ALL) and 2 acute leukemias of ambiguous lineage) had active disease status at the time of transplantation. The preparative regimen included myeloablative conditioning based on either total body irradiation or treosulfan or melphalan. A haploidentical related donor was used as a graft source in 38 cases, while a fully matched related or unrelated donor was used in 5 cases. The engraftment was observed in 93% of cases, no excessive toxicity was noted. MRD-negative complete remission was achieved in 37 patients (86%). The cumulative incidence of grade II–IV acute graft-versus-host disease (GvHD) was 10%, and the cumulative incidence of chronic GvHD was 5%. At 2 years, transplant-related mortality was 7%, relapse incidence was 52%, event-free survival was 41%, and overall survival was 51%. The overall survival rate for the AML group was 58% and 25% for the T-ALL group. Our data show that the addition of targeted agents to the conditioning regimens is safe, however, does not significantly improve the results of HSCT in the study cohort of patients.

Основные исходы аллогенной трансплантации гемопоэтических стволовых клеток (ТГСК) при химиорефрактерных формах острых лейкозов остаются неудовлетворительными в первую очередь за счет высоких рисков рецидива. Добавление в режимы кондиционирования комбинаций таргетных препаратов является потенциальным подходом к повышению антилейкемической активности ТГСК. Мы оценивали безопасность и потенциальную эффективность добавления комбинации венетоклакса, даратумумаба и плериксафора в схемы кондиционирования у детей с химиорефрактерными формами острых лейкозов, получивших аллогенную ТГСК на платформе TCRab/CD19-деплеции, на основании данных пилотного исследования, а также изучения ретроспективной когорты пациентов, прошедших аналогичную терапию по индивидуальным показаниям. Настоящее исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Все 43 оцениваемых пациента (33 с острым миелоидным лейкозом (ОМЛ), 8 с Т-клеточным острым лимфобластным лейкозом (Т-ОЛЛ) и 2 с острым лейкозом неопределенной линейности) на момент проведения аллогенной ТГСК имели статус активного заболевания. В основе миелоаблативного режима кондиционирования применялись тотальное облучение тела или треосульфан, или мелфалан. В качестве источника трансплантата для 38 пациентов использован гаплоидентичный донор, для 5 – полностью совместимый родственный или неродственный донор. Приживление трансплантата зафиксировано в 93% случаев, избыточной токсичности отмечено не было. МОБ (минимальная остаточная болезнь)-негативная ремиссия зафиксирована у 37 (86%) пациентов. Кумулятивный риск развития острой реакции «трансплантат против хозяина» (РТПХ) II–IV стадии составил 10%, хронической РТПХ – 5%. В течение 2 лет трансплантат-ассоциированная смертность составила 7%, риск развития рецидива – 52%, бессобытийная и общая выживаемость – 41% и 51% соответственно. Уровень общей выживаемости для подгруппы пациентов с ОМЛ составил 58%, для Т-ОЛЛ – 25%. Наши данные показывают, что добавление таргетных агентов в состав кондиционирования безопасно, однако не приводит к улучшению результатов ТГСК в изучаемой когорте пациентов.

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