B-ALL儿童和年轻成人阶段前CAR淋巴去除方案中的有理替代方案:氟达拉滨和环磷酰胺。
Rational Alternatives to Fludarabine and Cyclophosphamide-Based Pre-CAR Lymphodepleting Regimens in the Pediatric and Young Adult B-ALL Setting.
发表日期:2023 Apr 26
作者:
Sean Green, Liora Schultz
来源:
Cellular & Molecular Immunology
摘要:
淋巴减灭化疗(LD)已成为儿童/成人B细胞恶性肿瘤异种抗原受体T细胞(CAR)疗效的关键决定因素。临床试验证明了氟达拉滨/环磷酰胺(Flu/Cy)方案的优越性,从而采用了Flu/Cy作为CAR前LD的标准。在全球氟达拉滨短缺的情况下,考虑替代方案是及时的,但是有限的临床数据存在,特别是在儿科B-ALL CAR环境中。苯达莫司汀已在成人淋巴瘤的CD19-CAR前作为有效的LD使用。尽管在儿科CAR环境中的使用有限,但在儿童霍奇金病中已经建立了耐受性。克拉屈巴因是一种嘌呤核苷类似物,与氟达拉滨具有重叠的机制,但在前期白血病设置中毒性较高,因此在作为LD前CAR使用时应谨慎。我们回顾使用苯达莫司汀和克拉屈巴因的经验,作为考虑作为儿童B-ALL的氟达拉滨替代方案的资源。 © 2023年。作者(s)独家许可Springer Science+Business Media,LLC的一部分,属于Springer Nature。
Lymphodepleting chemotherapy (LD) has emerged as a key determinant of chimeric antigen receptor T cell (CAR) efficacy across pediatric/adult B cell malignancies. Clinical trials demonstrate the superiority of fludarabine/cyclophosphamide (Flu/Cy) regimens, resulting in the adoption of Flu/Cy as the pre-CAR LD standard. In the context of a global fludarabine shortage, consideration of alternative regimens is timely, yet limited clinical data exists, specifically in the pediatric B-ALL CAR setting.Bendamustine has been used as an effective LD prior to CD19-CAR in adult lymphoma. Although use in the pediatric CAR setting is limited, tolerability has been established in pediatric Hodgkin's lymphoma. Clofarabine is a purine nucleoside analog with mechanistic overlap with fludarabine; however, toxicity is high in the upfront leukemia setting, and thus use as an LD pre-CAR should be pursued with caution. We review the experience using bendamustine and clofarabine to serve as a resource when considering LD regimens as an alternative to fludarabine for pediatric B-ALL.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.