Герпес-вирусные инфекции у реципиентов аллогенной трансплантации гемопоэтических стволовых клеток с TCRaβи CD19 деплецией: факторы риска и прогноз

Статья в Elpub

Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2017; 16: 10-21

Герпес-вирусные инфекции у реципиентов аллогенной трансплантации гемопоэтических стволовых клеток с TCRaβи CD19 деплецией: факторы риска и прогноз

Богоявленская А. А., Лаберко А. Л., Шелихова Л. Н., Шеховцова Ж. Б., Балашов Д. Н., Воронин К. А., Курникова Е. Е., Боякова Е. В., Райкина Е. В., Бриллиантова В. В., Пирумова Р. П., Масчан М. А.

https://doi.org/10.24287/1726-1708-2017-16-1-10-21

Аннотация

В данной работе исследованы распространенность и клиническое значение герпес-вирусных инфекций - цитомегаловирусной (ЦМВ) и Эпштейн-Барр-вирусной (ЭБВ) - у реципиентов алло-генной трансплантации гемопоэтических стволовых клеток (аллоТГСК) с TCRaβ и CD19 деплецией трансплантата. При использовании данного метода в трансплантате остаются преимущественно неаллореактивные TCRgd лимфоциты, что снижает риск развития реакции «трансплантат про-тив хозяина» (РТПХ) при сохранении потенциала контроля вирусных инфекций. Проанализиро-ваны результаты 182 ТГСК от гаплоидентичных и неродственных доноров у пациентов в возрасте до 23 лет со злокачественными и незлокачественными заболеваниями. Кумулятивная вероят-ность (КВ) возникновения ЦМВ-инфекции составила 51% (95% ДИ 44-60). В моно- и мультива-риантных анализах получено значимое влияние на риск ЦМВ-виремии, предшествующей острой РТПХ > II стадии, серопозитивности реципиента до ТГСК и наличия у пациента злокачественного заболевания. КВ ЭБВ-инфекции - 33% (95% ДИ 26-42). Фактором риска ЭБВ-виремии являлась острая РТПХ > II стадии. Манифестация ЦМВ болезни отмечена у 11 (6%) пациентов, ЭБВ-ассо-циированной посттрансплантационной болезни (ПТЛБ) - у 1 (0,5%). Развитие ЦМВ и ЭБВ-виремии не приводит к снижению показателей выживаемости после ТГСК. TCRaβ и CD19 деплеция транс-плантата ассоциированы cо значимой частотой развития ЦМВ-виремии, не влияющей на выжи-ваемость и трансплантатассоциированную смертность пациентов после аллоТГСК, и минималь-ным риском развития ПТЛБ.Ключевые слова: герпес-вирусные инфекции, TCRaβ-деплеция, аллогенная ТГСК.

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Pediatric Hematology/Oncology and Immunopathology. 2017; 16: 10-21

Herpesvirus infection following allogenic hematopoietic stem cell transplantation with TCRαβ and CD19 depletion: risk factors and outcome

Bogoyavlenskaya A. A., Laberko A. L., Shelikhova L. N., Shekhovtsova Z. B., Balashov D. N., Voronin K. A., Kurnikova E. E., Boyakova E. V., Raykina E. V., Brilliantova V. V., Pirumova R. P., Maschan M. A.

https://doi.org/10.24287/1726-1708-2017-16-1-10-21

Abstract

In this study we evaluated incidence and risk factors of Herpesvirus infections – Cytomegalovirus (CMV) и Epstein–Barr (EBV) – in recipients of allogenic hematopoietic stem cell transplantation (alloHSCT) with TCRαβ and CD19 depletion of graft. The usage of this method results to graft preservation of non-alloreactive TCRgd lymphocytes, leading to decresed risks of graft versus host disease (GVHD) with adequate antiviral control. We estimated the outcomes of 182 HSCT from haploidentical and unrelated donors in patients younger than 23 years old with malignant anf nonmalignant disoders. The cumulative incidence (Cum Inc) of CMV infection was 51% (95% CI 44–60). By uni- and multivariate analyzes was found the significant influence on CMV-viremia of acute GVHD grade 2–4, recipient’s seropositivity before HSCT and patient’s malignant disoder. Cum Inc of EBV infection was 33% (95% CI 26–42). The risk factor of EBV viremia was acute GVHD grade 2–4. The incidence of CMV-disease was 6% (11 patients), EBV-related posttransplant lymphoproliferative disoder (PTLD) 0,5% (1 patient). CMV and EBV viremia did not decrease survival after HSCT.
TCRαβ and CD19 depletion of graft was associated with significant risk of CMV viremia in patients after alloHSCT, but did not influence survival and transplant related mortality, and with extremely low risk of PTLD development.

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