{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:10:45Z","timestamp":1792239045116,"version":"4.4.0"},"reference-count":38,"publisher":"American Society of Hematology","issue":"14","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,2]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>We developed an allogeneic matched donor CD19 chimeric antigen receptor (CAR) product (CAR\u2013donor lymphocyte infusion [DLI]) for adult patients with B-cell acute lymphoblastic leukemia (B-ALL) after failure of allogeneic stem-cell transplantation (allo-SCT). We evaluate the risks and benefits of pre\u2013CAR-DLI lymphodepleting chemotherapy (LD) and the efficacy of repeat CAR-DLI dosing per conventional DLI protocols. Primary outcomes were toxicity and feasibility of CAR-DLI manufacture; secondary outcomes included CAR-DLI engraftment, expansion, and persistence. A total of 17 allo-SCT donors received leukapheresis and 14 patients with B-ALL (median age, 43 years) received infusion. Median disease burden at registration was 50.5% bone marrow blasts (range, measurable residual disease [MRD] to 100%). Patients 1 to 7 received CAR-DLI alone (CAR-DLI-alone); patients 8 through 14 received CAR-DLI and LD with fludarabine\/cyclophosphamide (CAR-DLI+LD). CAR-DLI+LD vs CAR-DLI-alone was associated with superior peak CAR-DLI engraftment (93\u2009134 vs 8010 copies per \u03bcg genomic DNA [gDNA]), expansion (858\u2009101 vs 39\u2009038 copies per \u03bcg gDNA per 28 days) and persistence (median, 197 vs 32 days). CAR-DLI+LD was not associated with more immunotoxicity than CAR-DLI-alone, and graft-versus-host disease (GVHD; grade 1, skin) affected only 2 of 14 patients (14%). CAR-DLI+LD vs CAR-DLI-alone conferred superior event-free-survival and overall survival at 12 months (57% vs 29%; 83% vs 29%). Repeat CAR-DLI dosing was administered to 8 of 14 (57%) patients with morphological\/MRD+ relapse, but with minimal engraftment\/expansion or toxicity\/efficacy. CAR-DLI+LD has a tolerable safety profile without significant GVHD and is associated with significantly better outcomes than CAR-DLI-alone. Repeat CAR-DLI dosing beyond dose 1 was not found to be effective in this analysis. This trial was registered at www.clinicaltrials.gov as #NCT02893189.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2025028790","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:16:30Z","timestamp":1752236190000},"page":"1664-1676","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Matched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-5858","authenticated-orcid":false,"given":"Claire","family":"Roddie","sequence":"first","affiliation":[{"name":"1Research Department of Haematology, Cancer Institute, University College London, London, United Kingdom"},{"name":"2Department of Haematology, University College London Hospitals, London, United 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