急性T淋巴细胞白血病MRD导向治疗进展

Progress in MRD-Directed Therapy for T-Cell Acute Lymphoblastic Leukemia

摘要: 目的：梳理急性T淋巴细胞白血病(T-ALL)中微小残留病(MRD)导向治疗的证据基础及个体化决策价值，阐明MRD与分子分型、异基因造血干细胞移植(allo-HSCT)、CAR-T细胞治疗及靶向治疗的整合路径。方法：围绕T-ALL分子异质性、一线治疗优化、MRD检测时点、allo-HSCT、复发/难治救治、CAR-T及靶向药物进展进行综述，重点分析MRD在治疗强度调整、桥接移植和复发预警中的作用。结果：MRD已由疗效评价指标转变为贯穿诱导、巩固、移植前后及复发监测的核心枢纽。奈拉滨整合、风险适应性强化、allo-HSCT精准选择、CD7/CD5 CAR-T桥接，以及维奈克拉、达雷妥尤单抗、NOTCH和JAK/IL7R通路抑制等策略，推动T-ALL由经验性强化走向分子分型与MRD共同驱动的分层管理。结论：以MRD动态监测为主线，联合分子分型、细胞治疗、移植和靶向药物制定个体化方案，是改善T-ALL长期结局的重要方向；未来需统一MRD平台与阈值，并明确不同人群MRD阳性后的干预策略。

Abstract: Objective: To review the evidence base and individualized decision-making value of measurable residual disease (MRD)-directed therapy in T-cell acute lymphoblastic leukemia (T-ALL), and to clarify the integrated pathway linking MRD with molecular subtyping, allogeneic hematopoietic stem cell transplantation (allo-HSCT), CAR-T cell therapy, and targeted therapy. Methods: This review focuses on the molecular heterogeneity of T-ALL, optimization of frontline therapy, MRD monitoring time points, allo-HSCT, salvage treatment for relapsed/refractory disease, CAR-T cell therapy, and advances in targeted agents, with emphasis on the role of MRD in treatment-intensity adjustment, bridging to transplantation, and early relapse warning. Results: MRD has evolved from a response-assessment indicator into a central hub throughout induction, consolidation, pre- and post-transplant evaluation, and relapse monitoring. The incorporation of nelarabine, risk-adapted intensification, precise selection for allo-HSCT, CD7/CD5 CAR-T bridging, and strategies involving venetoclax, daratumumab, NOTCH pathway inhibition, and JAK/IL7R pathway inhibition are promoting a shift in T-ALL management from empirical intensification toward stratified treatment jointly driven by molecular subtyping and MRD. Conclusion: Individualized treatment plans based on dynamic MRD monitoring and integrated with molecular subtyping, cellular therapy, transplantation, and targeted agents represent an important direction for improving long-term outcomes in T-ALL. Future studies should standardize MRD platforms and thresholds and clarify intervention strategies for MRD-positive patients across different populations.