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环磷酰胺治疗 CD19 靶向 CAR-T 细胞治疗后难治性免疫效应细胞相关神经毒性综合征

英文原题:Cyclophosphamide for the Treatment of Refractory Immune Effector Cell-Associated Neurotoxicity Syndrome Following CD19-Targeted CAR T-Cell Therapy.

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Cyclophosphamide for the Treatment of Refractory Immune Effector Cell-Associated Neurotoxicity Syndrome Following CD19-Targeted CAR T-Cell Therapy.

PubMed 2025/12/24(内容时间) J Med Cases Q3 · IF 0.5(JCR 2025)

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中文摘要

免疫效应细胞相关神经毒性综合征(ICANS)是CAR-T 细胞治疗的严重并发症,可导致显著发病和死亡。糖皮质激素和阿那白滞素是治疗基石,但部分患者会出现重度、糖皮质激素难治性ICANS,凸显了对更有效疗法的迫切需求。本文报告一名51岁男性,患复发/难治性费城染色体阳性(Ph⁺)B细胞急性淋巴细胞白血病(B-ALL),接受brexucabtagene autoleucel CAR-T 治疗后发生4级ICANS。其神经毒性对大剂量糖皮质激素、阿那白滞素和鞘内化疗均无应答。给予低剂量环磷酰胺(375 mg/m²)后,患者神经功能完全恢复。该病例提示,较早使用较低剂量环磷酰胺可能在保留CAR-T 功能的同时有效减轻ICANS,值得进一步研究以明确其在治疗流程中的定位。

展开英文摘要原文

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a serious complication of chimeric antigen receptor T-cell (CAR-T) therapy, associated with significant morbidity and mortality. While corticosteroids and anakinra are cornerstones of treatment, a subset of patients develop severe, steroid-refractory ICANS, highlighting a critical need for more effective therapies.

We present the case of a 51-year-old male with relapsed/refractory Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL) who developed grade 4 ICANS following brexucabtagene autoleucel CAR-T therapy. His neurotoxicity was refractory to high-dose corticosteroids, anakinra, and intrathecal chemotherapy.

Following administration of low-dose cyclophosphamide (375 mg/m 2 ), patient achieved full neurological recovery. This case suggests that earlier, lower-dose cyclophosphamide may be an effective strategy to mitigate ICANS while preserving CAR-T function, warranting further investigation to define its role in treatment algorithms.

论文信息

作者
Frisch A、Marino L、Alsaadi D、Kasarabada A、Hua G、Ajebo G、Medlin S、Gul Z
第一作者单位
Department of Internal Medicine, Inova Fairfax Medical Center, Falls Church, VA, USA.United States
通讯作者单位
Inova Schar Cancer Center, Inova Fairfax Medical Center, Fairfax, VA, USA.United States
文献类型
病例报告
期刊
Journal of medical cases2026 Jan
原文标识
PubMed 41487336 · DOI 10.14740/jmc5211