{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:10:20Z","timestamp":1785798620769,"version":"3.56.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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<jats:sub>max<\/jats:sub>, AUC<jats:sub>0-28d<\/jats:sub>, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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, <jats:italic>p<\/jats:italic> = 0.021) and female sex (HR = 0.235, <jats:italic>p<\/jats:italic> = 0.032) as independent protective factors for LFS. Cellular kinetics analysis showed effective <jats:italic>in vivo<\/jats:italic> expansion in 98% of patients, with a median C<jats:sub>max<\/jats:sub> of 30,860 copies\/\u03bcg DNA and a median time-to-peak of 10.5 days. The MRD-CR group at day 28 exhibited significantly higher C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0-28d<\/jats:sub> (<jats:italic>p<\/jats:italic> = 0.017; <jats:italic>p<\/jats:italic> = 0.029) and superior CAR-T persistence (<jats:italic>p<\/jats:italic> = 0.030) compared to the non-MRD-CR group. Pre-infusion tumor burden levels did not significantly impact CAR-T expansion or duration. BCA duration positively correlated with CAR-T persistence (r=0.570, <jats:italic>p<\/jats:italic> &amp;lt; 0.001), but CAR-T expansion parameters (Cmax and AUC0-28d) did not significantly influence BCA. Regarding safety, grade \u22653 CRS occurred in 16% of patients, and ICANS in 10%. Pre-infusion MRD \u2265 10<jats:sup>-3<\/jats:sup> was an independent predictor of severe CRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CD19 CAR-T therapy demonstrates highly effective MRD clearance and provides long-term survival benefits with a manageable safety profile in pediatric B-ALL patients with MRD positivity or chemotherapy intolerance. Effective CAR-T expansion occurs even at low tumor burdens. These findings support the potential for advancing CAR-T therapy into earlier treatment lines, although its value requires further validation in prospective studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1672509","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:22:31Z","timestamp":1759728151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effective MRD clearance and long-term survival with CD19 CAR-T in pediatric B-ALL patients with MRD positivity or chemotherapy 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