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预测 B 细胞急性淋巴细胞白血病 CAR-T 细胞治疗结局的生物标志物:系统综述

英文原题:Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review.

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Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review.

PubMed 2025/10/16(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

尽管已有一些有前景的见解,但毒性分级系统的异质性、生物标志物阈值的不一致以及回顾性研究设计限制了临床标准化。未来方向强调减瘤桥接治疗、生物标志物指导的组合策略(例如针对 TP53 突变的 MDM2 抑制剂),以及整合预测模型的多中心验证,以优化个性化 CAR-T 治疗策略。

研究思路结论见上方概要

嵌合抗原受体(CAR)T细胞疗法已经彻底改变了复发/难治性B细胞急性淋巴细胞白血病(B-ALL)的治疗,但细胞因子释放综合征(CRS)、神经毒性(ICANS)以及长期疗效可变等挑战仍然存在。本系统综述评估了生物标志物在预测CAR-T 治疗结局、毒性风险以及指导个体化治疗策略中的作用。

遵循PRISMA指南,我们系统检索了PubMed、Web of Science和Embase中2018-2024年发表的研究。共纳入33项研究,涉及2,095例患者进行分析。

关键发现确定了肿瘤负荷和微小残留病(MRD)作为双重预测性生物标志物。高肿瘤负荷(原始细胞≥40%)与完全缓解率降低(87% vs. 100%)及CRS/ICANS风险增加相关,而MRD阴性(NGS阈值<10⁻⁶)预测更优的2年无事件生存率(68% vs. 23%)。CAR-T 功能参数,包括PD-1/LAG-3表达(CD4+细胞中>5.2%)和峰值扩增动力学,将疗效与毒性权衡相关联。遗传生物标志物(IKZF1突变、复杂核型)和生化指标(m-EASIX >6.2、铁蛋白≥10,000 ng/mL)进一步分层风险。单向疗效生物标志物包括T细胞亚群(如CD8+初始T细胞)和B细胞再生障碍,而IL-6动态特异性预测CRS严重程度。

展开英文摘要原文

Following PRISMA guidelines, we systematically searched PubMed, Web of Science, and Embase for studies published between 2018-2024. A total of 33 studies involving 2,095 patients were included in the analysis.

Key findings identified tumor burden and minimal residual disease (MRD) as dual-predictive biomarkers. High tumor burden ( 40% blasts) correlated with reduced complete remission rates (87% vs. 100%) and increased CRS/ICANS risks, while MRD negativity (NGS threshold <10 ) predicted superior 2-year event-free survival (68% vs. 23%). CAR-T functional parameters, including PD-1/LAG-3 expression (>5.2% in CD4+ cells) and peak expansion kinetics, linked efficacy to toxicity trade-offs. Genetic biomarkers (IKZF1 mutations, complex karyotypes) and biochemical indicators (m-EASIX >6.2, ferritin 10,000 ng/mL) further stratified risks. Unidirectional efficacy biomarkers included T-cell subsets (e.g., CD8+ naive T cells) and B-cell aplasia, while IL-6 dynamics specifically predicted CRS severity. DISCUSSION: Despite promising insights, heterogeneity in toxicity grading systems, inconsistent biomarker thresholds, and retrospective study designs limit clinical standardization. Future directions emphasize cytoreductive bridging therapies, biomarker-guided combinatorial approaches (e.g., MDM2 inhibitors for TP53 mutations), and multicenter validation of integrated predictive models to optimize personalized CAR-T therapy strategies.

论文信息

作者
Ke Y、Zhou F
单位
Department of Paediatric Hematology and Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei,&#xa0;China.China
文献类型
系统综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41181124 · DOI 10.3389/fimmu.2025.1656108