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多发性骨髓瘤 CAR-T 细胞治疗后迟发性致死性神经毒性:一例病例报告

英文原题:Delayed fatal neurotoxicity in post CAR-T cell therapy for multiple myeloma, a case report.

查看英文原题

Delayed fatal neurotoxicity in post CAR-T cell therapy for multiple myeloma, a case report.

PubMed 2026/03/03(内容时间) Leuk Res Rep Q4 · IF 0.8(JCR 2025)

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中文摘要

抗BCMA CAR-T 细胞疗法,特别是ciltacabtagene autoleucel,已显著改善复发/难治性多发性骨髓瘤(RRMM)的预后。虽然早发性免疫效应细胞相关神经毒性综合征(ICANS)是公认的并发症,但迟发性和非ICANS神经系统综合征,如运动与神经认知毒性(MNT),带来了独特的诊断和治疗挑战。

我们报告一例61岁女性,有15年RRMM病史,在ciltacabtagene autoleucel输注后50天出现严重的迟发性神经毒性。临床过程以意识模糊起病,并迅速进展为4级ICANS,表现为嗜睡、强直和帕金森样特征。系列MRI影像显示基底节和脑干出现进展性、对称性T2/FLAIR高信号,以及反应性硬脑膜炎。尽管采取了积极的多模式免疫抑制治疗,患者病情仍难治,并于第93天死亡。尸检证实严重的双侧海马硬化、弥漫性胶质增生和小胶质细胞浸润。本病例突出表现为一种与新兴MNT表型重叠的致死性迟发性神经毒性。随着CAR-T 疗法的推广,本病例强调了延长临床警惕的必要性以及对难治性迟发性神经毒性新型管理策略的迫切需求。

展开英文摘要原文

Anti-BCMA CAR T-cell therapy, specifically ciltacabtagene autoleucel, has significantly improved outcomes for relapsed/refractory multiple myeloma (RRMM). While early-onset immune-effector cell-associated neurotoxicity syndrome (ICANS) is a recognized complication, delayed-onset and non-ICANS neurological syndromes, such as movement and neurocognitive toxicity (MNT), present unique diagnostic and therapeutic challenges.

We report a case of a 61-year-old female with a 15-year history of RRMM who developed severe, delayed neurotoxicity 50 days after ciltacabtagene autoleucel infusion. The clinical course began with confusion and rapidly progressed to grade 4 ICANS characterized by lethargy, rigidity, and parkinsonian features. Serial MRI imaging revealed evolving, symmetric T2/FLAIR hyperintensities in the basal ganglia and brainstem, and reactive pachymeningitis.

Despite aggressive multi modal immunosuppression, the patient's condition remained refractory and expired on day 93. Post-mortem autopsy confirmed severe bilateral hippocampal sclerosis, diffuse gliosis, and microglial infiltration. This case highlights a fatal presentation of delayed neurotoxicity that overlaps with the emerging MNT phenotype. As CAR-T therapies expand, this case underscores the necessity for prolonged clinical vigilance and the urgent need for novel management strategies for refractory, late-onset neurotoxicity.

论文信息

作者
Khoudari H、Shoaib A、Nashatizadeh M、Ahmed N、Lutfi F、Mushtaq M、Shune L、Singh A
第一作者单位
University of Debrecen, Debrecen, Hungary.Hungary
通讯作者单位
Division of hematologic Malignancies and Cellular therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, Wyandotte.
文献类型
病例报告
期刊
Leukemia research reports2026
原文标识
PubMed 41853755 · DOI 10.1016/j.lrr.2026.100577