肿瘤细胞治疗研究
英文原题：Long-Term Cognitive Impairment After CAR-T Therapy Versus Autologous Stem Cell Transplantation: A Propensity Score-Matched Cohort Study.
Long-Term Cognitive Impairment After CAR-T Therapy Versus Autologous Stem Cell Transplantation: A Propensity Score-Matched Cohort Study.
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本回顾性倾向评分匹配队列研究使用TriNetX美国协作网络数据（2014年1月至2025年4月）。为确保同期比较，将ASCT患者的索引日期限制为2017年8月及以后。CAR-T 患者与ASCT患者按人口学特征、疾病、合并症、既往及同期治疗和实验室指标进行1:1匹配。主要终点为按ICD-10编码定义的认知障碍发生时间。
比较3067例CAR-T 患者（中位随访634天）和3067例ASCT患者（中位随访713天）后发现，CAR-T 患者认知障碍风险更高（HR=1.58；95% CI：1.39–1.80；p<0.001）。由于风险不满足比例风险假设（Schaenfeld检验p<0.001），研究还采用限制性平均生存时间（RMST）表示差异：CAR-T 患者在1年和2年时保持无认知障碍的时间分别约少25天和53天（均p<0.001）。风险在30天时最高（HR=4.22；95% CI：3.23–5.53）；排除急性ICANS时间窗的30天和90天对照分析中，风险仍升高（HR分别为1.30和1.25，均p<0.05）。CAR-T 后神经功能障碍更常见，尤其是脑病（HR=2.04；95% CI：1.73–2.40）。相反，CAR-T 与继发性急性髓系白血病风险降低相关（HR=0.46；95% CI：0.38–0.55；p<0.001）。
CAR-T 治疗与认知障碍风险升高相关，且这种关联持续至急性期之后。由于数据为基于编码的观察性资料，应将结果解读为相关性，而非特定机制的证据；研究结果提示需要在知情同意中讨论相关风险、开展长期神经认知监测并开发神经保护策略。
Background/Objectives : Chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes in relapsed or refractory hematologic malignancies, but long-term cognitive outcomes remain poorly understood.
We compared the incidence and time course of cognitive impairment and associated neurological complications after CAR-T therapy compared with autologous stem cell transplantation (ASCT). Methods : This retrospective, propensity-matched cohort study utilized the TriNetX US Collaborative Network (January 2014-April 2025). To ensure concurrent comparisons, ASCT recipients were restricted to an index date beginning in August 2017 or later. CAR-T recipients were matched 1:1 to ASCT recipients for demographics, disease, comorbidities, prior and concomitant treatments, and laboratory parameters. The primary endpoint was time to cognitive impairment, as defined by ICD-10 codes. Results : After comparing 3067 CAR-T patients (median follow-up 634 days) with 3067 ASCT patients (median follow-up 713 days), CAR-T recipients had a higher risk of cognitive impairment (HR 1. 58; 95% CI 1. 39-1. 80; p < 0. 001). Because the risks were not proportional (Schaenfeld p < 0.
001), the difference was also expressed as restricted median survival time (RMST): CAR-T recipients spent approximately 25 and 53 days fewer days without cognitive impairment at 1 and 2 years, respectively (both p < 0. 001). The risk was greatest at 30 days (HR 4. 22; 95% CI 3. 23-5. 53), but remained elevated in control analyses at 30 and 90 days that excluded the acute ICANS window (HR 1. 30 and 1. 25, respectively; both p < 0. 05). Neurological dysfunction, particularly encephalopathy (HR 2. 04; 95% CI 1. 73-2. 40), was more common after CAR-T.
Conversely, CAR-T was associated with a reduced risk of secondary acute myeloid leukemia (HR 0. 46; 95% CI 0. 38-0. 55; p < 0. 001). Conclusions : CAR-T therapy is associated with a higher risk of cognitive impairment that persists beyond the acute phase. As these are observational, code-based data, they should be interpreted as associations rather than evidence of a specific mechanism, and they highlight the need for informed consent discussions, long-term neurocognitive monitoring, and the development of neuroprotective strategies.
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