{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:49:24Z","timestamp":1790660964912,"version":"4.1.0"},"reference-count":205,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"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:p>Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R\/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release syndrome (CRS) and neurotoxicity, B-cell aplasia-associated hypogammaglobulinemia and agammaglobulinemia, and the alloreactivity of allogeneic CAR-Ts. Furthermore, recent advances such as improvements in media design, the reduction of <jats:italic>ex vivo<\/jats:italic> culturing duration, and other phenotype-determining factors can still create room for a more effective CAR-T therapy in R\/R B-ALL. Herein, we review preclinical and clinical strategies with a focus on novel studies aiming to address the mentioned hurdles and stepping further towards a milestone in CAR-T therapy of B-ALL.<\/jats:p>","DOI":"10.3389\/fimmu.2021.765097","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T07:29:03Z","timestamp":1635406143000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward"],"prefix":"10.3389","volume":"12","author":[{"given":"Pouya","family":"Safarzadeh Kozani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooria","family":"Safarzadeh 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