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氟达拉滨短缺是否使当前的淋巴细胞清除范式转向苯达莫司汀?

英文原题:Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?

查看英文原题

Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?

PubMed 2023/11/22(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

CAR-T 细胞输注前最常用的淋巴细胞清除方案是环磷酰胺(CY)联合氟达拉滨(Flu)(CY-FLU)。尽管环磷酰胺(CY)具有淋巴细胞毒性作用,却同时保留调节性T细胞活性,可能影响CAR-T 细胞疗效。此外,氟达拉滨(FLU)与神经毒性相关,这可能妨碍对CAR-T 治疗中观察到的免疫效应细胞相关神经毒性综合征(ICANS)进行早期识别。鉴于FLU持续短缺,必须采用替代性淋巴细胞清除药物。迄今直接比较不同淋巴细胞清除方案的研究数量有限,且多数为回顾性研究。本文综述淋巴系统血液系统恶性肿瘤CAR-T 治疗前淋巴细胞清除的现有文献,特别关注苯达莫司汀(BEN)。近期证据提示,CAR-T 输注前给予BEN可获得与CY-FLU相当的疗效,且毒性特征可能更有利。这一发现值得通过随机前瞻性研究进一步评估。

展开英文摘要原文

The most common lymphodepletion regimen used prior to infusion of chimeric antigen receptor-T cells (CAR-T) is cyclophosphamide (CY) in combination with fludarabine (Flu) (CY-FLU). While cyclophosphamide (CY) possesses lymphotoxic effects, it concurrently preserves regulatory T cell activity, potentially affecting the efficacy of CAR-T cells.

Moreover, the use of fludarabine (FLU) has been linked to neurotoxicity, which could complicate the early detection of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in CAR-T cell therapy. Given the ongoing shortage of FLU, alternative lymphodepleting agents have become necessary. To date, only a limited number of studies have directly compared different lymphodepleting regimens, and most of these comparisons have been retrospective in nature.

Herein, we review the current literature on lymphodepletion preceding CAR-T cell therapies for lymphoid hematologic malignancies, with a specific focus on the use of bendamustine (BEN). Recent evidence suggests that administering BEN before CAR-T cell infusion yields comparable efficacy, possibly with a more favorable toxicity profile when compared to CY-FLU. This warrants further investigation through randomized prospective studies.

论文信息

作者
Filioglou D、Husnain M、Khurana S、Simpson RJ、Katsanis E
单位
Department of Pediatrics, University of Arizona, Tucson, AZ, United States.United States
文献类型
综述
期刊
Frontiers in immunology2023
原文标识
PubMed 38077398 · DOI 10.3389/fimmu.2023.1329850