Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children34110.24287/1726-1708-2020-19-2-71-82ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИThe efficacy of the regimens of “graft versus host” disease prophylaxis after hematopoietic stem cell transplantation from unrelated donors in children: single center experienceЭффективность режимов профилактики реакции «трансплантат против хозяина» после трансплантации гемопоэтических стволовых клеток от неродственного донора у детей: опыт одного Центраhttps://orcid.org/0000-0003-3797-5808SidorovaN. V.СидороваН. В.
Russian Federation

Head of the Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation,

Russia, 115478, Moscow, Kashirskoe Shosse, 23

заведующая отделением детской трансплантации костного мозга и гемопоэтических стволовых клеток,

115478, Москва, Каширское шоссе, 23

valerevna25@mail.ruhttps://orcid.org/0000-0002-2021-0465SlininA. S.СлининА. С.
Russian Federation
https://orcid.org/0000-0003-2395-4045MachnevaE. B.МачневаЕ. Б.
Russian Federation
https://orcid.org/0000-0002-2652-8642KonstantinovaV. V.КонстантиноваВ. В.
Russian Federation
https://orcid.org/0000-0003-4170-7152BuryaA. E.БуряА. Е.
Russian Federation
https://orcid.org/0000-0002-4569-657XPristanskovaE. A.ПристансковаЕ. А.
Russian Federation
https://orcid.org/0000-0002-1587-3256lagonravovaO. L.БлагонравоваО. Л.
Russian Federation
https://orcid.org/0000-0003-4431-1444SkorobogatovаE. V.СкоробогатоваЕ. В.
Russian Federation
https://orcid.org/0000-0002-2945-284XKirgizovK. I.КиргизовК. И.
Russian Federation
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииDmitry 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 РоссииRussian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Healthcare of Russian FederationОбособленное структурное подразделение Российская детская клиническая больница ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России0207202019271820107202001072020Copyright ©; 2020, «D. Rogachev NMRCPHOI»Copyright ©; 2020, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2020«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/341

Graft versus host” disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The optimal model of GvHD prophylaxis in allo-HSCT from alternative donors in children currently remains actual question. Materials and methods. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian Federation. Two hundred fifty six allo-HSCT were made during the period 2003–2019 from matched unrelated donors (MUD). Age median was 7.1 years old. The source of hematopoietic stem cells (HSCs) bone marrow – 76% (n = 194), peripheral blood stem cells – 24% (n = 62). GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolate mofetil (MMF), in following combinations Tacro/Mtx (n = 98), Tacro/MMF (n = 102), tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Median follow-up 8.9 years. GvHD prophylaxis regimen did not affect significantly the toxicity of therapy (toxicity: severe mucositis grade III–IV, nephrotoxicity, hepatotoxicity) (p = 0.4; p = 0.24; p = 0.62 respectively). In our study the rate of the overall survival (ОS) has significant differences in depending of the source of prevention GvHD. The using a combination of tacrolimus and cyclosporine with low doses of methotrexate had a positive effect on OS (p = 0.035) in patients of common non-malignant and malignant groups, as well as on the level of 2-year relapse-free survival in the group of children with malignant disorders (p = 0.671). In the general group the OS the worst results were achieved when MMF was included in the prophylaxis model. In this experience of treating of a large cohort of patients the choice of calcineurin inhibitors and methotrexate as the agent GvHD prophylaxis showed the efficacy and safety for non-manipulated MUD for both malignant and non-malignant diseases in children.

Реакция «трансплантат против хозяина» (РТПХ) – одно из самых частых и опасных осложнений аллогенной трансплантации гемопоэтических стволовых клеток (ТГСК). Вопрос оптимального режима профилактики РТПХ при трансплантациях от альтернативных доноров у детей в настоящее время остается нерешенным. Материалы и методы. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России. В анализ вошли 256 ТГСК от неродственных доноров, проведенных в 2003–2019 гг., медиана возраста пациентов 7,1 года. Источник гемопоэтических стволовых клеток (ГСК): костный мозг (КМ) – 76% (n = 194), периферические стволовые клетки крови (ПСКК) – 24% (n = 62). Профилактика РТПХ включала препараты такролимус (Tacro), циклоспорин А (CsA), метотрексат (Mtx), микофенолата мофетил (MMF) в комбинациях Tacro/Mtx (n = 98), Tacro/MMF (n = 102), Tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Медиана наблюдения составила 8,9 года. Достоверного влияния на токсичность терапии (мукозит желудочно-кишечного тракта III–IV степени, нефротоксичность, гепатотоксичность) комбинация агентов для профилактики РТПХ не оказала (p = 0,4; p = 0,24 и p = 0,62 соответственно). В нашем исследовании показано, что наилучшие результаты были достигнуты при использовании комбинации Tacro/CsA с низкими дозами Mtx, применение которых положительно влияло на общую выживаемость (p = 0,035) у пациентов всех нозологических групп, а также на уровень 2-летней безрецидивной выживаемости в группе детей со злокачественными заболеваниями (p = 0,671). В общей группе пациентов при оценке общей выживаемости отмечено, что худшие результаты были достигнуты при включении в режим профилактики MMF. На опыте лечения большой группы пациентов были показаны эффективность и безопасность применения режимов профилактики РТПХ при неродственных трансплантациях неманипулированных ГСК на базе блокаторов кальциневрина и Mtx как для злокачественных, так и незлокачественных заболеваний у детей.

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