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CAR-T 治疗肺移植后 R/R PTLD:一项多中心回顾性研究

英文原题:CAR-T for Management of R/R PTLD Following Lung Transplant: A Multi-center Retrospective Study.

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CAR-T for Management of R/R PTLD Following Lung Transplant: A Multi-center Retrospective Study.

PubMed 2025/10/10(内容时间) Transplant Cell Ther Q1 · IF 4.7(JCR 2025)

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中文摘要

背景:实体器官移植后淋巴增殖性疾病(PTLD)是一种罕见恶性肿瘤;肺移植受者的进展率和死亡率明显较高。靶向CD19的CAR-T 细胞治疗复发/难治性B细胞淋巴瘤已显示疗效,但其在PTLD中的作用研究不足,尤其是肺移植人群。我们开展一项多中心回顾性研究,报告3例肺移植受者接受阿基仑赛(Axicel)治疗R/R PTLD的情况。所有患者既往均接受过多线治疗,包括化学免疫治疗;其中1例还接受过EBV特异性T细胞治疗(Tabelecleucel)。CAR-T 治疗后3例均达到完全或部分缓解,但其中1例随后发生移植物排斥。淋巴细胞清除期间暂停免疫抑制治疗(IST),CAR-T 后则根据排斥与复发/再发风险,个体化决定是否及何时恢复IST。所有病例均发生CRS,但程度较轻,发生于CAR-T 后早期,采用托珠单抗(可联合或不联合地塞米松)有效控制。本研究凸显CAR-T 治疗肺移植受者PTLD的可行性,患者应答令人鼓舞,毒性可管理。CAR-T 输注前后应审慎、个体化调整IST,以平衡治疗效力和复发风险,同时保护肺移植物。病例也揭示了目前CAR-T 研究的局限:高危且免疫学情况复杂的这类患者常被排除在外;亟需更多该人群的研究报告,以深入了解CAR-T 治疗前后IST的管理。

展开英文摘要原文

Post-transplant lymphoproliferative disorder (PTLD) is a rare malignancy following solid organ transplantation (SOT), with lung transplant recipients experiencing disproportionately high rates of progression and mortality. While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated efficacy in relapsed/refractory (R/R) B-cell lymphoma, its role in PTLD remains underexplored, particularly in lung SOT.

We present a multi-center retrospective study of three lung transplant recipients treated with Axicabtagene ciloleucel (Axicel) for R/R PTLD. All patients had received multiple lines of prior therapy, including chemoimmunotherapy, with one patient also receiving EBV-specific T-cell therapy (Tabelecleucel). CAR-T therapy resulted in complete or partial response in all three patients, although one subsequently developed allograft rejection. Immunosuppression (IST) was held at the time of lymphodepletion and re-introduced variably post-CAR-T depending on risk of rejection versus risk of relapse/recurrence.

Cytokine release syndrome (CRS) was observed in all cases but was mild, occurred early post-CAR-T, and managed effectively with tocilizumab with/without dexamethasone Our study highlights the feasibility of CAR-T therapy in lung SOT recipients with PTLD, with promising responses and manageable toxicities.

Individualized and judicious modification of IST around CAR-T infusion is critical to balance efficacy and disease relapse with lung allograft preservation. These cases highlight the limitations of current CAR-T studies, which have excluded this high-risk, immunologically complex patient population, and underscore the need for further publications in this patient subset to better understand how to manage IST around CAR-T.

论文信息

作者
Salter B、Suleman A、Kridel R、Trottier AM、Li R、Binnie M、Balitsky AK、Davies GA
单位
Department of Oncology, Juravinski Hospital & Cancer Centre, Hamilton, Ontario, Canada. Electronic address: brittany.salter@medportal.ca.Canada
文献类型
多中心研究
期刊
Transplantation and cellular therapy2026 Feb
原文标识
PubMed 41076192 · DOI 10.1016/j.jtct.2025.10.006