{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:32:15Z","timestamp":1790742735152,"version":"4.1.0"},"reference-count":36,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH Medical Research Scholars Program","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"National Cancer Institute, National Institutes of Health","award":["ZIA BC 012187"],"award-info":[{"award-number":["ZIA BC 012187"]}]},{"name":"Division of Intramural Research of the National Institute of Allergy and Infectious Diseases","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,22]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Despite the curative potential for chimeric antigen receptor (CAR) T-cells in B-cell acute lymphoblastic leukemia (B-ALL), efficacy can be limited by life-threatening adverse events such as severe infections. As immune effector cell-associated hematotoxicity and secondary immunodeficiency may be particularly profound in B-ALL, understanding pre-infusion risk of severe infection is imperative. The ALL-HEMATOTOX (ALL-HT) score is a recently validated tool designed to predict CAR-associated hematotoxicity in B-ALL, but the relationship between ALL-HT and severe infections post-infusion has not yet been comprehensively assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this multicenter, retrospective analysis, we evaluated ALL-HT and other pre-infusion variables for an association with severe infection through day+60 (D+60) in patients with B-ALL treated with CD19 and CD22-based CAR T-cell constructs across three institutions. Infections were identified by microbiology, histopathology, or as a clinical syndrome and graded by CTCAE (Common Terminology Criteria for Adverse Events) V.5.0. Severe infections were defined as grade\u22653. Multivariable logistic regression and Cox proportional hazard models were constructed to identify independent risk factors for infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Across 350 patients receiving CAR T-cells, 79 (23%) developed a severe infection within day+60 post-CAR, including 8 patients with grade 4 (life-threatening) infection and 5 patients with grade 5 (fatal) infections. Bloodstream infections were the most common, comprising 67% of those with severe infections. In multivariable analysis, pre-infusion factors associated with severe infection included older age (OR 1.35 (1.1\u20131.6), p=0.002), prior severe infection (OR 2.1 (1.2\u20133.7), p=0.009), and a higher ALL-HT score (OR 1.15 (1.01\u20131.31), p=0.04). Patients classified as high-risk (HR) by ALL-HT had a greater risk of infection compared with low-risk patients (HR 1.4 (1.1\u20132.7), p=0.014).<\/jats:p>\n                  <jats:p>Multiple severe infections occurred in 24 patients (7%). In a subanalysis, ALL-HT risk of infection was primarily driven by baseline thrombocytopenia, with a cut-off of\u226450\u2009000 platelets\/\u00b5L strongly predicting risk of infection (HR 2.2 (1.3\u20133.6), p=0.002). Post-infusion infection risk was driven by a longer duration of neutropenia (OR 1.26 (1.1\u20131.4), p&lt;0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Older age, prior infection history, baseline thrombocytopenia, and higher ALL-HT scores are strong independent risk factors for severe infection among patients with B-ALL receiving CAR T-cells. These factors may guide individualized risk mitigation to prevent severe infections in this high-risk patient population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03827343\">NCT03827343<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2025-012436","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:44:04Z","timestamp":1759931044000},"page":"e012436","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03827343","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03827343","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03827343","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"August A.","family":"Culbert","sequence":"first","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"},{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Gava","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis K.","family":"Valtis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Satta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surabhi","family":"Vora","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Rocco","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases Division of Intramural Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Nussenblatt","sequence":"additional","affiliation":[{"name":"National Institutes of Health, National Institute of Allergy and Infectious Diseases Division of Intramural Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara K","family":"Silbert","sequence":"additional","affiliation":[{"name":"National Institutes of Health, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen","family":"Shalabi","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Yates","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae H.","family":"Park","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"Lamble","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3905-0251","authenticated-orcid":false,"given":"Kai","family":"Rejeski","sequence":"additional","affiliation":[{"name":"Medizinische Klinik III, LMU Klinikum Gro\u00dfhadern Medizinische Klinik III, Munchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8474-9080","authenticated-orcid":false,"given":"Nirali N.","family":"Shah","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"2025091422351946000_13.9.e012436.1","doi-asserted-by":"crossref","first-page":"978","DOI":"10.3324\/haematol.2019.238634","article-title":"Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma","volume":"106","author":"Logue","year":"2021","journal-title":"Haematologica"},{"key":"2025091422351946000_13.9.e012436.2","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-020-00346-7","article-title":"Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma","volume":"10","author":"Wudhikarn","year":"2020","journal-title":"Blood Cancer 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Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis. 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