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TCR-α/β和CD19去除移植物的儿科受者中巨细胞病毒和EB病毒感染的危险因素及其临床影响

Risk Factors for and the Clinical Impact of Cytomegalovirus and Epstein-Barr Virus Infections in Pediatric Recipients of TCR-α/β- and CD19-Depleted Grafts.

作者信息

Laberko Alexandra, Bogoyavlenskaya Anna, Shelikhova Larisa, Shekhovtsova Zhanna, Balashov Dmitriy, Voronin Kirill, Kurnikova Elena, Boyakova Elena, Raykina Elena, Brilliantova Varvara, Pirumova Valentina, Novichkova Galina, Maschan Alexei, Maschan Michael

机构信息

Clinical Immunology Unit, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

出版信息

Biol Blood Marrow Transplant. 2017 Mar;23(3):483-490. doi: 10.1016/j.bbmt.2016.12.635. Epub 2016 Dec 27.

DOI:10.1016/j.bbmt.2016.12.635
PMID:28039080
Abstract

Alpha/beta T cell and CD19 depletion are used to improve the outcomes of hematopoietic stem cell transplantation (HSCT). We evaluated the burden of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in pediatric patients after this HSCT type. A cohort of 182 patients with malignant (n = 114) or nonmalignant (n = 68) disorders was transplanted from either matched unrelated (n = 124) or haploidentical (n = 58) donors. The cumulative incidence of CMV and EBV viremia were 51% and 33%, respectively. Acute graft-versus-host disease (GVHD) grades II to IV, D-/R+ serology, and malignant HSCT indications were associated with increased risk of CMV viremia. CMV disease developed in 10 patients (6%). The occurrence of CMV viremia was not associated with inferior outcomes. Acute GVHD grade ≥ II was the only factor significantly associated with an increased risk of EBV viremia. Rituximab significantly decreased the rate of EBV reactivation in a subgroup that received a higher B cell dose in the graft. The rate of EBV-associated disease was .5%, and EBV viremia did not affect survival. TCR-α/β and CD19 depletion are associated with a significant rate of CMV viremia that does not affect survival. The hazard of EBV post-transplant lymphoproliferative disease (PTLD) is eliminated by the combination of CD19 depletion and rituximab.

摘要

α/β T细胞和CD19清除术用于改善造血干细胞移植(HSCT)的疗效。我们评估了此类HSCT术后儿科患者的巨细胞病毒(CMV)和EB病毒(EBV)感染负担。182例患有恶性疾病(n = 114)或非恶性疾病(n = 68)的患者队列接受了来自匹配无关供者(n = 124)或单倍体相合供者(n = 58)的移植。CMV和EBV病毒血症的累积发生率分别为51%和33%。急性移植物抗宿主病(GVHD)II至IV级、D-/R+血清学以及恶性HSCT指征与CMV病毒血症风险增加相关。10例患者(6%)发生了CMV疾病。CMV病毒血症的发生与较差的预后无关。急性GVHD≥II级是与EBV病毒血症风险增加显著相关的唯一因素。利妥昔单抗在移植中接受较高B细胞剂量的亚组中显著降低了EBV再激活率。EBV相关疾病的发生率为0.5%,EBV病毒血症不影响生存。TCR-α/β和CD19清除与显著的CMV病毒血症发生率相关,但不影响生存。CD19清除与利妥昔单抗联合使用可消除移植后淋巴增殖性疾病(PTLD)的EBV风险。

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