Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children25510.24287/1726-1708-2019-18-3-9-21PROMISING STUDIESПЕРСПЕКТИВНЫЕ ИССЛЕДОВАНИЯUnknownLow-dose infusions of CD45RA depleted donor lymphocytes after TCRα/β-depleted transplantation in patients with non-malignant disordersПрименение профилактических инфузий СD45RA-деплетированных донорских лимфоцитов у пациентов, перенесших аллогенную трансплантацию гемопоэтических стволовых клеток с TCRαβ - и CD19-деплецией по поводу заболеваний незлокачественной природыhttps://orcid.org/0000-0001-8754-1376BlagovS. L.БлаговС. Л.
Russian Federation

Sergei L. Blagov, MD, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

117997, Moscow, Samory Mashela st., 1

Благов Сергей Львович, врач-гематолог отделения ТГСК № 1

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

sblagov89@gmail.comhttps://orcid.org/0000-0003-0520-5630ShelikhovaL. N.ШелиховаЛ. Н.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0003-2689-0569BalashovD. N.БалашовД. Н.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0002-1873-3486OsipovaE. Y.ОсиповаЕ. Ю.
Russian Federation

Moscow

Москва

sblagov89@gmail.comEfimenkoM. V.ЕфименкоМ. В.
Russian Federation

Moscow

Москва

sblagov89@gmail.comKhripkovaN. A.ХрипковаН. А.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0003-3513-8299MuzalevskiyJ. O.МузалевскийЯ. О.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0002-1384-1752DunaikinaM. A.ДунайкинаМ. А.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0002-6481-8608PershinB. S.ПершинБ. С.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0002-0016-6698MaschanA. A.МасчанА. А.
Russian Federation

Moscow

Москва

sblagov89@gmail.comhttps://orcid.org/0000-0003-1735-0093MaschanM. A.МасчанМ. А.
Russian Federation

Moscow

Москва

sblagov89@gmail.comDmitriy 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 России130920191839211209201912092019Copyright ©; 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/255

Viral infections are frequent causes of failure among the recipients of the HSCT with graft TCRα/β and CD19depletion. Adoptive transfer of memory T-cells by CD45RA-depleted donor lymphocytes infusions (memory DLI) may be useful in control of viral infections. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The work reflects the retrospective data analysis of 51 patients with non-malignant disorders who had received low dose memory DLI after HSCT. Up to 3 doses of donor lymphocytes were administered. Median follow-up for alive patients was 30 (18–49) months. We did not observe any allergic reactions, septic complications after memory DLI. The cumulative incidence of a de novo acute GVHD after DLI was 10% (95% CI: 4–22). Among 41% patients (n = 21) was detected CMV in the blood. In 73% of them (n = 16) CMV was detected before first DLI. Among patients who received DLI, 53% (n = 27) had documented appearance of virus-specific lymphocytes in peripheral blood (ELISPOT assay).Thus, the infusion of memory T-cells at a dose of 25–100 αβ 103/kg body weight of the recipient for CD3+ in the case of HSCT from a haploidentical donor and 100–300 αβ 103/kg for an unrelated HSCT. Infusions of low dose memory T-lymphocytes after transplant engraftment are safe, potentially effective and constitute a simple measure to prevent infections in the setting of alpha/beta T-cell-depleted transplantation.

Вирусные инфекции – ведущая причина негативных исходов терапии у реципиентов аллогенной трансплантации гемопоэтических стволовых клеток (ТГСК) с TCRαβ- и CD19-деплецией трансплантата. Мы предположили, что инфузии низких доз СD45RA-деплетированных донорских лимфоцитов (ИДЛ) могут помочь в обеспечении контроля над вирусными инфекциями. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ. В работе проанализированы результаты применения низких доз ИДЛ в группе пациентов с незлокачественными гематологическими и иммунологическими заболеваниями. Медиана кратности введения клеточного продукта – 3 инфузии; медиана наблюдения для живых пациентов – 30 мес. Аллергических реакций, септических осложнений после ИДЛ не отмечено. Кумулятивная вероятность de novo острой реакции «трансплантат против хозяина» (оРТПХ) после ИДЛ составила 10%. У 21 (41%) пациента выявлен цитомегаловирус (ЦМВ) в крови; у 16 (73%) пациентов с ЦМВ-виремией вирус выявлен до 1-го введения клеток памяти. Среди пациентов, получивших ИДЛ, у 27 (53%) документировано появление вирус-специфичных лимфоцитов в периферической крови. Таким образом, введение T-клеток памяти после приживления трансплантата в дозе 25–100 ´ 103/кг массы тела реципиента в случае ТГСК от гаплоидентичного донора и 100–300 ´ 103/кг для неродственной совместимой ТГСК с TCRαβ- и СD19-деплецией – безопасный и потенциально эффективный способ обеспечения защиты от вирусных инфекций.

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