nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.17650/2311-1267-2018-5-4-31-39nodgo-439Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESАнализ донор-ассоциированных факторов при неродственных трансплантациях гемопоэтических стволовых клеток у детей с незлокачественными заболеваниямиAnalysis of donor-associated factors in unrelated transplantations of hematopoietic stem cells in children with non-malignant diseaseshttps://orcid.org/0000-0003-3797-5808СидороваН. В.SidorovaN. V.

Наталья Валерьевна Сидорова 

врач-гематолог отделения трансплантации костного мозга 

Hematologist Department of Bone Marrow Transplantation

valerevna25@mail.ruhttps://orcid.org/0000-0002-2945-284XКиргизовК. И.KirgizovK. I.

к.м.н., заместитель директора Института управления и трансляционной медицины 

Cand. of Sci. (Med.), Deputy Director of the Institute of Management and Translational Medicine

kirgiz-off@yandex.ruhttps://orcid.org/0000-0002-2021-0465СлининА. С.SlininA. S.

научный сотрудник отдела исследований лимфопролиферативных заболеваний

Researcher Department for Research on Lymphoproliferative Diseases

alekseislinin@gmail.comhttps://orcid.org/0000-0002-4569-657XПристансковаЕ. А.PristanskovaE. A.

заведующая отделением гематологии и химиотерапии № 1 

Head of the Department of Hematology and Chemotherapy № 1

eprist82@mail.ruhttps://orcid.org/0000-0002-2652-8642КонстантиноваВ. В.KonstantinovaV. V.

врач-гематолог отделения трансплантации костного мозга 

Hematologist Department of Bone Marrow Transplantation

veronika_md@mail.ruhttps://orcid.org/0000-0003-4170-7152БуряА. Е.BuryaA. E.

врач-гематолог отделения трансплантации костного мозга

Hematologist Department of Bone Marrow Transplantation

burya.a.e@gmail.comhttps://orcid.org/0000-0003-4496-1156ПерсианцеваМ. И.PersiantsevaM. I.

научный сотрудник отдела оптимизации лечения и профилактики трансплантации гемопоэтических стволовых клеток

Researcher Department for Optimization of Treatment and Prevention of Hematopoietic Stem Cell Transplantation

persiantseva@mail.ruhttps://orcid.org/0000-0002-1587-3256БлагонравоваО. Л.BlagonravovaO. L.

врач клинической лабораторной диагностики отделения трансплантации костного мозга

Doctor of Clinical Laboratory Diagnosis of the Bone Marrow Transplantation Department

bla-oksana@yandex.ruhttps://orcid.org/0000-0003-4431-1444СкоробогатоваЕ. В.SkorobogatovaE. V.

д.м.н., заведующая отделением трансплантации костного мозга 

Dr. of Sci. (Med.), Head of Bone Marrow Transplantation Department

skorobog.e@mail.ruРоссийская детская клиническая больница ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияRussian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian FederationРоссийская детская клиническая больница ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава РоссииРоссияRussian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian FederationФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава РоссииРоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian Federation201821012019543139Copyright © Сидорова Н.В., Киргизов К.И., Слинин А.С., Пристанскова Е.А., Константинова В.В., Буря А.Е., Персианцева М.И., Благонравова О.Л., Скоробогатова Е.В., 20192019Сидорова Н.В., Киргизов К.И., Слинин А.С., Пристанскова Е.А., Константинова В.В., Буря А.Е., Персианцева М.И., Благонравова О.Л., Скоробогатова Е.В.Sidorova N.V., Kirgizov K.I., Slinin A.S., Pristanskova E.A., Konstantinova V.V., Burya A.E., Persiantseva M.I., Blagonravova O.L., Skorobogatova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/439

Выбор оптимального донора при отсутствии HLA-совместимого родственника, а также анализ рисков трансплантации гемопоэтических стволовых клеток (ТГСК) крайне актуален, в особенности у пациентов с незлокачественными заболеваниями. В статье выполнен анализ 99 аллогенных ТГСК от неродственных доноров в отделении трансплантации костного мозга Российской детской клинической больницы. В анализ были включены пациенты с приобретенными и врожденными формами незлокачественных заболеваний. Выбор оптимального неродственного донора при отсутствии совместимого родственного донора, а также анализ рисков проведения терапии требует изучения факторов, влияющих на результат лечения у данной группы пациентов. Было показано, что уровень 2-летней общей выживаемости (ОВ) составил 74 % (стандартное отклонение ± 4,7 %). При этом клинические проявления острой реакции «трансплантат против хозяина» I–IV степени зарегистрированы у 67 % (n = 66) больных, а тяжелые формы III–IV степени – у 13 % (n = 13) детей. Хроническая форма реакции «трансплантат против хозяина» (хрРТПХ) наблюдалась у 29 % (n = 29) пациентов. При изучении факторов, связанных с донором, было обнаружено негативное влияние различий по системе HLA на частоту развития хрРТПХ – у (9/10) HLA-несовместимого донора она была выше на 29 % (р = 0,019). Увеличение возраста донора на каждые 10 лет последовательно снижает ОВ на 9–11 % (р = 0,117), однако ОВ с донором старше 46 лет составила 100 % (n = 7). Не было обнаружено влияния на ОВ следующих по совместимости с реципиентом факторов: по полу, группе крови, серостатус по цитомегаловирусу (ЦМВ). Отмечено, что сочетание ЦМВ-позитивного серостатуса донора и негативного статуса реципиента увеличивает риск отторжения трансплантата до 50 % в сравнении с другими вариантами ЦМВ-серостатуса (р = 0,001). В целом была отмечена возможность выполнения ТГСК от неродственного донора для пациентов с незлокачественными заболеваниями и возможные пути подбора оптимального донора.

Конфликт интересов

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов. 

Финансирование

Финансирование. Исследование проведено без спонсорской поддержки. 

The choice of the optimal donor in the absence of an HLA-compatible relative, as well as the analysis of the risks of hematopoietic stem cell transplantation (HSCT), is extremely important, especially in patients with non-cancerous diseases. The article analyzes 99 allogeneic HSCTs from unrelated donors in the bone marrow transplantation department of the Russian Children’s Clinical Hospital. The analysis included patients with acquired and congenital forms of non-malignant diseases. The choice of an optimal unrelated donor in the absence of a compatible relative donor, as well as an analysis of the risks of treatment, requires studying the factors that influence the outcome of treatment in this group of patients. It was shown that the level of 2-year overall survival (OS) was 74 % (standard deviation ± 4.7 %). At the same time, clinical manifestations of the acute graft versus host disease of grade I–IV were recorded in 67 % (n = 66) of patients, and severe forms of grade III–IV in 13 % (n = 13) of children. Chronic graft versus host disease (chGVHD) was observed in 29 % (n = 29) patients. When studying the factors associated with the donor, it was found that the differences in the HLA system have a negative effect on the incidence of chGVHD; in a (9/10) HLA-incompatible donor, it was 29 % higher (p = 0.019). Increasing the age of the donor for every 10 years consistently reduces the OS by 9–11 % (p = 0.117), however, the OS with a donor over 46 years old was 100 % (n = 7). No effect on the agents with respect to the following factors with respect to the recipient was found: by sex, blood group, serostatus for cytomegalovirus (CMV). It was noted that the combination of CMV-positive serostatus of the donor and the negative status of the recipient increases the risk of transplant rejection up to 50 % in comparison with other variants of CMV serostatus (p = 0.001). In general, the possibility of performing HSCT from an unrelated donor for patients with non-malignant diseases and possible ways of selecting the optimal donor was noted. 

Conflict of interest

Conflict of interest. The authors declare no conflict of interest.

Funding

Funding. The study was performed without external funding.

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The authors declare that there are no conflicts of interest present.