Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children24110.24287/1726-1708-2019-18-2-22-29ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИEvaluation of abatacept for GVHD prophylaxis in patients with non-malignant diseases after hematopoietic stem cell transplantationОценка эффективности использования абатацепта для профилактики острой реакции «трансплантат против хозяина» после трансплантации гемопоэтических стволовых клеток у детей с незлокачественными заболеваниямиhttps://orcid.org/0000-0002-7696-1153RadyginaS. A.РадыгинаС. А.
Russian Federation

Svetlana A. Radygina, MD, hematologist.

117997, Moscow, Samory Mashela st., 1.

Радыгина Светлана Анатольевна, врач-гематолог отделения ТГСК № 2.

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

ra-svet-7@yandex.ruhttps://orcid.org/0000-0003-3949-248XVasilievaA. P.ВасильеваА. П.
Russian Federation
https://orcid.org/0000-0002-1754-1220KozlovskayaS. N.КозловскаяС. Н.
Russian Federation
https://orcid.org/0000-0001-8687-5497ShipitsynaI. P.ШипицынаИ. П.
Russian Federation
https://orcid.org/0000-0002-8545-0507LivshitsA. M.ЛившицА. М.
Russian Federation
https://orcid.org/0000-0002-3800-8927GutovskayaE. I.ГутовскаяЕ. И.
Russian Federation
https://orcid.org/0000-0003-0520-5630ShelikhovaL. N.ШелиховаЛ. Н.
Russian Federation
https://orcid.org/0000-0003-2689-0569BalashovD. N.БалашовД. Н.
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 России2906201918222292806201928062019Copyright ©; 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/241

Graft-versus-host diseases (GVHD) is one of most significant complication after allogeneic hematopoietic stem cells transplantation (HSCT). T-cell activation is a major stage in the GVHD pathogenesis. T-cells require 2 signals for activation: cognate antigen/MHC binding T-cell receptors and positive costimulatory signals from antigen-presenting cells (APC). The predominant positive costimulatory signal to human CD4 T0-cells comes through the CD28 receptor. This signal can be blocked by fusion proteins (such as CTLA4-Ig). Abatacept is a soluble fusion protein, which links the extracellular domain of human CTLA-4 to the modified Fc portion of human IgG1. We present results of single-center prospective randomized study to evaluate the efficacy of adding abatacept to the GVHD prophylaxis protocol after hemopoietic stem cell transplantation in patients with non-malignant diseases. Study was approved by Ethics Committee and Scientific Council of the Institute (protocol # 9/2013 from 01.10.2013). During 4 years we included 62 patients, 30 of them received abatacept as additional agent. Cumulative incidence of acute GVHD was significantly lower in this group in compare with control group (p = 0,018). When we stratified patients in dependents of graft processing technology, we did not see any advantages of abatacept in patients after transplantation with TCRαβ+/СD19+ graft depletion. However, after HSCT with non-manipulated graft the abatacept showed significant efficacy in aGVHD prophylaxis compared with control group (p = 0,024). Abatacept can be recommended as effective additional agent for GVHD prophylaxis after allogeneic HSCT in patients with non-malignant diseases.

Реакция «трансплантат против хозяина» (РТПХ) – одно из наиболее значимых осложнений алло- генной трансплантации гемопоэтических стволовых клеток (ТГСК). Абатацепт представляет собой растворимую гибридную белковую молекулу, состоящую из двух компонентов – внеклеточного домена CTLA4 человека и модифицированного Fc фрагмента IgG1. Связываясь с CD80/СD86, он блокирует костимуляторный сигнал с антигенпрезентирующей клетки на СD28 Т-лимфоцита и предотвращает его активацию. Таким образом, применение абатацепта может влиять на ранний этап патогенеза острой РТПХ. Цель исследования – изучение эффективности и безопасности применения абатацепта в качестве дополнительного иммуносупрессивного агента в стандартных для клиники протоколах профилактики острой РТПХ у пациентов с незлокачественными заболеваниями. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ (протокол № 9/2013 от 01.10.2013). С 2013 по 2018 год в исследование были включены 62 пациента; в 30 случаях в качестве дополнительного препарата использовали абатацепт, включенный в стандартный протокол профилактики РТПХ. При анализе эффективности абатацепта для профилактики острой РТПХ в исследуемой группе (n = 30) продемонстрированы значительные его преимущества (р = 0,018) по сравнению с контрольной группой (n = 32). При стратификации пациентов в зависимости от технологии подготовки трансплантата в группе пациентов, которым проводили TCRαβ+/СD19+ деплецию трансплантата, данных об эффективности абатацепта не получено (p = 0,28). При применении неманипулированного трансплантата (n = 23) преимущества использования абатацепта имели статистически достоверную значимость (p = 0,024). Абатацепт можно рекомендовать для включения в режимы профилактики РТПХ в качестве дополнительного агента при аллогенной ТГСК у пациентов с незлокачественными заболеваниями.

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