{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:00Z","timestamp":1787026560851,"version":"build-2736575974"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This umbrella review consolidates data from systematic reviews and meta-analyses on the efficacy and safety of Chimeric Antigen Receptor T-cell (CAR-T) therapy in hematologic malignancies. The aim is to assess CAR-T efficacy across different malignancies, identify key safety concerns, and provide clinical recommendations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a thorough search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews up to May 2024. Systematic reviews and meta-analyses evaluating CAR-T efficacy in hematologic malignancies were included. The AMSTAR tool was used to assess methodological quality, and the GRADE system was employed to evaluate the quality of evidence for each outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 105 meta-analyses met the inclusion criteria. CD19-targeted CAR-T therapies demonstrated superior efficacy in acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), particularly in relapsed or refractory cases (high-quality). However, CAR-T monotherapy showed reduced efficacy in central nervous system lymphoma (CNSL) (middle-quality). Combination therapies, particularly CAR-T with HSCT, improved complete response rates but were associated with increased severe adverse events, such as CRS and neurotoxicity (high-quality). Axi-cel was found to carry a higher risk of ICANS and neutropenia compared to Tisa-ce (high-quality), likely due to its CD28 costimulatory domains, which enhance T-cell activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CAR-T therapy demonstrates promising clinical outcomes in ALL and DLBCL, but significant safety concerns remain. Combining CAR-T with therapies such as HSCT improves efficacy but also heightens the risk of severe toxicities. Future research should focus on optimizing CAR-T constructs, refining preconditioning regimens, and identifying predictive biomarkers to personalize treatment and mitigate risks in vulnerable populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , identifier CRD42024581782.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1608768","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:37:04Z","timestamp":1763534224000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and safety of chimeric antigen receptor T-cell in the treatment of hematologic malignancy: an umbrella review 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meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhengyu","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41572-024-00525-x","article-title":"Acute 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