Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children50410.24287/1726-1708-2021-20-2-12-28ПЕРЕДОВАЯ СТАТЬЯThe safety and effctiveness of donor memory T lymphocyte infusions after hematopoietic stem cell transplantation with ab T cell depletion platform in children with acute leukemiaБезопасность и эффективность инфузий донорских лимфоцитов памяти после трансплантации гемопоэтических стволовых клеток на платформе деплеции ab-T-лимфоцитов у детей с острыми лейкозамиDunaykinaM. A.ДунайкинаМ. А.
Russian Federation
https://orcid.org/0000-0003-0520-5630ShelikhovaL. N.ШелиховаЛ. Н.
Russian Federation
ShekhovtsovaZh. B.ШеховцоваЖ. Б.
Russian Federation
GlushkovaS. Yu.ГлушковаС. Ю.
Russian Federation
NikolayevR. V.НиколаевР. В.
Russian Federation
BlagovS. L.БлаговС. Л.
Russian Federation
KhismatullinaR. D.ХисматуллинаР. Д.
Russian Federation
https://orcid.org/0000-0003-2689-0569BalashovD. N.БалашовД. Н.
Russian Federation
https://orcid.org/0000-0002-0566-053XSkvortsovaYu. V.СкворцоваЮ. В.
Russian Federation
KurnikovaE. E.КурниковаЕ. Е.
Russian Federation
PershinD. E.ПершинД. Е.
Russian Federation
ZubachenkoV. А.ЗубаченкоВ. А.
Russian Federation
MuzalevskyYa. O.МузалевскийЯ. О.
Russian Federation
KazachyonokA. S.КазаченокА. С.
Russian Federation
OsipovaE. Yu.ОсиповаЕ. Ю.
Russian Federation
https://orcid.org/0000-0003-1735-0093MaschanM. A.МасчанМ. А.
Russian Federation

 Michael A. Maschan, dr. med. sci., Deputy Director General –Director 

1 Samory Mashela St., Moscow 117997

 Масчан Михаил Александрович, д-р мед. наук, заместитель генерального директора – директор 

117997, Москва, ул. Саморы Машела, 1

Michael.Maschan@fccho-moscow.ruDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России2205202120212282005202120052021Copyright ©; 2021, «D. Rogachev NMRCPHOI»Copyright ©; 2021, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2021«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/504

T-cell ab depletion prevents “graft-versus-host” disease (GVHD), does not impair engraftment, and improves the outcomes of hematopoietic stem cell transplantation (HSCT) from a haploidentical donor. Memory T lymphocyte infusions (CD45RA-depleted) can transfer functional immunity to common pathogens to recipients. In a randomized study, we explored the safety and effctiveness of donor memory T lymphocyte infusions (DLI) in children with leukemia after HSCT with ab T cell depletion platform.  The study was approved by the Independent Ethics Committee and the Scientifi Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation. A total of 149 patients were enrolled in the study; 76 patients were randomly assigned to the DLI group and 73 patients were allocated to the control group. Donors were haploidentical related in 91% of cases. The myeloablative conditioning regimen included treosulfan and total body irradiation. Anti-thymocyte globulin (ATG) was excluded from the conditioning regimen, instead, we used a combination of abatacept and tocilizumab. Graft processing involved TCRab-/CD19-depletion. The main parameters of assessment included the cumulative risk of detection of cytomegalovirus (CMV) DNA and the cumulative risk of grade II–IV GVHD. The additional parameters of assessment were the cumulative risk of transplant-related mortality, the cumulative risk of relapse, the overall and event-free survival rates, and the parameters of immune recovery. A historical control group was used to compare the primary outcomes of HSCT with ATG and an alternative immunomodulatory regimen (abatacept and tocilizumab). The cumulative risk of grade II–IV GVHD was 14% in the experimental group and 12% in the control group (p = 0.8). The cumulative risk of CMV viremia was 45% and 55% in the experimental and control groups, respectively (p = 0.4). In the prospective cohort, the rates of transplant-related mortality, the cumulative risk of relapse, and the overall survival were 2%, 25%, and 80%, respectively, without statistical diffrence between the arms. In the experimental group, we noticed a tendency toward an increase in the proportion of patients who developed an immune response to CMV in the early post-HSCT period. The substitution of ATG with tocilizumab and abatacept was not accompanied by a higher incidence of GVHD or graft failure; it was associated with signifiantly lower transplant-related mortality rates (2% vs 13%, p = 0.002) and improved immune recovery in the early post-HSCT period. Prophylactic infusions of donor memory lymphocytes are safe and may be used for further improvement in. the results of HSCT with ab T cell depletion platform.

Деплеция ab-T-лимфоцитов предотвращает реакцию «трансплантат против хозяина» (РТПХ), не нарушает приживление трансплантата и улучшает исходы трансплантации гемопоэтических стволовых клеток (ТГСК) от гаплоидентичных доноров. Инфузии Т-лимфоцитов памяти (CD45RA-деплетированных) способны переносить функциональный иммунитет к распространенным патогенам. В рандомизированном исследовании мы изучили безопасность и эффективность инфузии донорских лимфоцитов (ИДЛ) памяти у детей с лейкозом после ТГСК на платформе ab-T-деплеции. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. В исследование включены 149 пациентов, 76 рандомизированы в группу ИДЛ, 73 – в контрольную группу. Доноры были гаплоидентичными родственными в 91% случаев. Миелоаблативное кондиционирование включало треосульфан или тотальное облучение тела (ТОТ). Антитимоцитарный глобулин (АТГ) был исключен из состава кондиционирования, вместо него применяли комбинацию абатацепта и тоцилизумаба. Процессинг трансплантата включал TCRab/CD19-деплецию. Основными параметрами оценки были кумулятивный риск детекции ДНК цитомегаловируса (ЦМВ) и кумулятивный риск РТПХ II–IV стадии. Дополнительными параметрами оценки являлись кумулятивный риск трансплантационной смертности, кумулятивный риск рецидива, общая и бессобытийная выживаемость, а также показатели восстановления иммунной системы. Группа исторического контроля была использована для сравнения основных исходов ТГСК при применении АТГ и альтернативной схемы иммуномодуляции (абатацепт и тоцилизумаб). Кумулятивный риск РТПХ II–IV стадии составил 14% в экспериментальной группе и 12% в контрольной группе (p = 0,8). Кумулятивный риск ЦМВ-виремии составил 45% в экспериментальной группе и 55% в контрольной группе (p = 0,4). В исследуемой когорте трансплантационная смертность, кумулятивный риск рецидива и общая выживаемость составили 2%, 25% и 80% соответственно без статистически достоверных различий между рукавами исследования. Выявлен тренд к увеличению доли пациентов, сформировавших иммунный ответ к ЦМВ на ранних сроках после ТГСК в экспериментальной группе. Замена АТГ на тоцилизумаб и абатацепт не сопровождалась повышением частоты РТПХ и недостаточности трансплантата и была ассоциирована с достоверным. снижением трансплантационной смертности (2% против 13%, p = 0,002) и улучшением показателей восстановления иммунной системы на ранних сроках после ТГСК. Профилактические инфузии донорских лимфоцитов памяти безопасны и могут быть использованы для дальнейшей оптимизации результатов ТГСК на платформе ab-T-деплеции.

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