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抗 CD19 CAR-T 疗法治疗 EBV 阴性移植后淋巴组织增生性疾病:单中心病例系列。

Anti-CD19 CAR-T therapy for EBV-negative posttransplantation lymphoproliferative disease-a single center case series.

机构信息

BMT Unit, Tel Aviv (Sourasky) Medical Center, Tel Aviv, Israel.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Bone Marrow Transplant. 2021 May;56(5):1031-1037. doi: 10.1038/s41409-020-01145-1. Epub 2020 Nov 23.

Abstract

Posttransplantation lymphoproliferative disease (PTLD) is a potentially fatal disorder arising after solid organ or hematopoietic cell transplantation. Survival rates of PTLD with diffuse large B-cell lymphoma (DLBCL) phenotype have improved due to the introduction of rituximab, however, reports on curative management of refractory PTLD are scarce. Here, we describe successful management of three patients with refractory EBV-negative PTLD with chimeric antigen receptor T-cell (CAR-T) therapy. All patients continued calcineurin inhibitors throughout the whole course of treatment. T-cell immunophenotyping was performed on both the apheresed cells and CAR-T product to investigate the T-cell compartment subpopulations. All three patients responded to a single infusion of tisagenlecleucel and two of them achieved CR. Toxicity profile was similar to other patients with non-PTLD DLBCL treated with CAR-T. No transplanted graft dysfunction was observed during the course of therapy. To our knowledge, this is the first report demonstrating that patients with EBV-negative refractory PTLD may benefit from CAR-T therapy, similarly to other patients with relapse/refractory DLBCL. A larger cohort of patients is needed to further establish proof-of-concept.

摘要

移植后淋巴组织增生性疾病(PTLD)是实体器官或造血细胞移植后发生的一种潜在致命疾病。由于利妥昔单抗的引入,具有弥漫性大 B 细胞淋巴瘤(DLBCL)表型的 PTLD 的存活率有所提高,但是关于难治性 PTLD 的治愈性治疗的报告很少。在这里,我们描述了三例用嵌合抗原受体 T 细胞(CAR-T)治疗难治性 EBV 阴性 PTLD 的成功管理经验。所有患者在整个治疗过程中均继续使用钙调磷酸酶抑制剂。对吸出的细胞和 CAR-T 产物进行 T 细胞免疫表型分析,以研究 T 细胞亚群。所有三名患者均对单次输注 tisagenlecleucel 有反应,其中两名患者达到完全缓解。毒性谱与用 CAR-T 治疗的其他非 PTLD DLBCL 患者相似。在治疗过程中未观察到移植物功能障碍。据我们所知,这是首例报道表明,EBV 阴性难治性 PTLD 患者可能受益于 CAR-T 治疗,与其他复发/难治性 DLBCL 患者相似。需要更大的患者队列来进一步证实这一概念。

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