Effective MRD clearance and long-term survival with CD19 CAR-T in pediatric B-ALL patients with MRD positivity or chemotherapy intolerance

作者：Yu Wang, Yueping Jia, Aidong Lu, Le‐Ping Zhang, Yu‐juan Xue, Huimin Zeng · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1672509 · 被引用次数：3 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Lymphoma Diagnosis and Treatment

Background While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy demonstrates remarkable efficacy in relapsed/refractory (R/R) ALL, its application in earlier treatment lines requires further investigation. This study aimed to evaluate the efficacy, safety, and cellular kinetics of CD19 CAR-T therapy in pediatric B-cell ALL (B-ALL) patients with minimal residual disease (MRD) positivity or chemotherapy intolerance. Methods Between 2017 and 2021, 50 eligible pediatric B-ALL patients (with positive MRD or chemotherapy intolerance) received CD19 CAR-T therapy. Efficacy endpoints included complete remission (CR), MRD-negative CR (MRD-CR), overall survival (OS), and leukemia-free survival (LFS). CAR-T cellular kinetics parameters (C max , AUC 0-28d , persistence) were quantified via qPCR and correlated with clinical outcomes. Safety assessment covered cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Results At day 28 post-infusion, the CR and MRD-CR rates were 98% and 96%, respectively. With a median follow-up of 68.7 months, the 5-year OS and LFS rates were 74.9% and 67.8%. Multivariate analysis identified prolonged B-cell aplasia (BCA) duration (HR = 0.969, p = 0.021) and female sex (HR = 0.235, p = 0.032) as independent protective factors for LFS. Cellular kinetics analysis showed effective in vivo expansion in 98% of patients, with a median C max of 30,860 copies/μg DNA and a median time-to-peak of ...