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儿童实体器官移植后移植后淋巴细胞增生性疾病的细胞毒性T淋巴细胞疗法

Cytotoxic T-lymphocyte therapy for post-transplant lymphoproliferative disorder after solid organ transplantation in children.

作者信息

Chiou Fang Kuan, Beath Sue V, Wilkie Gwen M, Vickers Mark A, Morland Bruce, Gupte Girish L

机构信息

Liver Unit (Including Small Bowel Transplantation), Birmingham Women's and Children's Hospital Foundation NHS Trust, Birmingham, UK.

Paediatric Gastroenterology, KK Women's and Children's Hospital, Singapore City, Singapore.

出版信息

Pediatr Transplant. 2018 Mar;22(2). doi: 10.1111/petr.13133. Epub 2018 Feb 1.

Abstract

EBV-CTL immunotherapy targets EBV antigens expressed by tumor cells in PTLD. Data on outcome of EBV-CTL in pSOT patients are limited. The aim of the study is to describe our experience with allogeneic, third-party EBV-CTL for the treatment of PTLD in pSOT patients in a single tertiary center. Retrospective review was performed of all pSOT patients who received EBV-CTL for PTLD. PTLD was diagnosed using World Health Organization histologic criteria. EBV-CTLs were derived from human leukocyte antigen-typed, EBV-seropositive third-party donors, and cryopreserved and maintained by an accredited national blood transfusion service. Ten patients received EBV-CTL for histologically proven PTLD from 1999 to 2016 following liver (n=5), combined intestinal/liver (n=4), and liver/kidney (n=1) transplantation. PTLD occurred at median age of 40 months (range: 12-144) and median post-transplant interval of 8 months (range: 2-107). Seven had monomorphic, two had polymorphic, and one had Hodgkin-type PTLD. All were of B-cell origin and EBV-positive on histology. EBV-CTL achieved an overall remission rate of 80% (8 of 10). Transient adverse effects included fever, tachycardia, and vomiting. None developed graft-versus-host disease or opportunistic infections. EBV-CTL is an effective treatment for PTLD in pSOT patients, with good remission rate and minimal toxicity.

摘要

EBV特异性细胞毒性T淋巴细胞免疫疗法靶向移植后淋巴组织增生性疾病(PTLD)中肿瘤细胞所表达的EBV抗原。关于实体器官移植(pSOT)患者接受EBV特异性细胞毒性T淋巴细胞治疗结果的数据有限。本研究的目的是描述我们在单一三级中心使用异体第三方EBV特异性细胞毒性T淋巴细胞治疗pSOT患者PTLD的经验。对所有接受EBV特异性细胞毒性T淋巴细胞治疗PTLD的pSOT患者进行回顾性分析。PTLD采用世界卫生组织组织学标准进行诊断。EBV特异性细胞毒性T淋巴细胞来源于人类白细胞抗原分型、EBV血清学阳性的第三方供体,并由经认可的国家输血服务机构进行冷冻保存和维护。1999年至2016年期间,10例患者在肝移植(n = 5)、肠/肝联合移植(n = 4)和肝/肾联合移植(n = 1)后,因组织学证实的PTLD接受了EBV特异性细胞毒性T淋巴细胞治疗。PTLD发生的中位年龄为40个月(范围:12-144个月),移植后的中位间隔时间为8个月(范围:2-107个月)。7例为单形性,2例为多形性,1例为霍奇金型PTLD。所有病例均为B细胞起源,组织学检查EBV呈阳性。EBV特异性细胞毒性T淋巴细胞的总体缓解率为80%(10例中的8例)。短暂的不良反应包括发热、心动过速和呕吐。无一例发生移植物抗宿主病或机会性感染。EBV特异性细胞毒性T淋巴细胞是治疗pSOT患者PTLD的有效方法,缓解率高且毒性极小。

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