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造血干细胞移植后严重病毒感染的儿科患者中,使用 CliniMACS Prodigy CCS(IFN-γ)系统从第三方供体中选择病毒特异性 T 细胞的早期经验。

Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation.

机构信息

Pediatric Hematology and Stem Cell Transplantation Department.

Hematology and Stem Cell Transplantation Department, United St. István and St. László Hospital, Budapest, Hungary.

出版信息

J Immunother. 2018 Apr;41(3):158-163. doi: 10.1097/CJI.0000000000000197.

Abstract

Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

摘要

病毒激活是异基因造血干细胞移植的常见并发症,尤其是在儿童中。对于难治性病例,最好在几天内实施快速的病毒特异性 T 细胞治疗。在我们的 43 例儿童异基因移植队列中,1 年内有 9 例符合病毒特异性 T 细胞治疗标准。病毒感染分别由 3 例巨细胞病毒(CMV)、2 例 EBV 和 1 例腺病毒(AdV)引起,3 例患者检测到多种病毒。需要 T 细胞治疗的病毒疾病包括 CMV 肺炎和结肠炎、AdV 肠炎和膀胱炎,以及 EBV 引起的移植后淋巴组织增生性疾病。细胞是在单核细胞白细胞分离后 24 小时内通过 CliniMACS Prodigy CCS(IFN-γ)系统生产的。8 例患者完全无症状,7 例患者也清除了病毒。6 例患者无病毒病或后遗症,中位随访 535(350-786)天,外周血中病毒 DNA 清除。1 例 CMV 肺炎患者因呼吸功能衰竭死亡。2 例患者的病毒病有所改善或清除,但患者死于侵袭性曲霉病。未发现移植物抗宿主病、排斥反应、器官毒性或复发性感染。CliniMACS Prodigy CCS(IFN-γ)系统实施的病毒特异性 T 细胞治疗是一种自动化、快速、安全且可能有效的方法,可控制儿科造血干细胞移植后耐药性病毒病。

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