{"doi":"10.1136/jitc-2025-012436","title":"Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL","abstract":"BACKGROUND: 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. METHODS: 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≥3. Multivariable logistic regression and Cox proportional hazard models were constructed to identify independent risk factors for infection. RESULTS: 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 (1.1-1.6), p=0.002), prior severe infection (OR 2.1 (1.2-3.7), p=0.009), and a higher ALL-HT score (OR 1.15 (1.01-1.31), 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 (1.1-2.7), p=0.014).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≤50 000 platelets/µL strongly predicting risk of infection (HR 2.2 (1.3-3.6), p=0.002). Post-infusion infection risk was driven by a longer duration of neutropenia (OR 1.26 (1.1-1.4), p<0.001). CONCLUSIONS: 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. TRIAL REGISTRATION NUMBER: NCT03827343.","journal":"Journal for ImmunoTherapy of Cancer","year":2025,"id":524441,"datarank":0.24437636577705454,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.002960678911939465,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.002960678911939465,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03827343"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1397951,"name":"Flavia Gava","orcid":"0000-0001-5888-6666","position":1,"is_corresponding":false},{"id":1240644,"name":"Yannis K. Valtis","orcid":"0000-0001-8927-8006","position":2,"is_corresponding":false},{"id":970975,"name":"Toshihisa Satta","orcid":"0000-0003-1712-5566","position":3,"is_corresponding":false},{"id":336111,"name":"Surabhi B Vora","orcid":"0000-0002-9344-5185","position":4,"is_corresponding":false},{"id":529097,"name":"Joseph M. Rocco","orcid":"0000-0003-4307-4934","position":5,"is_corresponding":false},{"id":640095,"name":"Véronique Nussenblatt","orcid":"0000-0002-9530-0131","position":6,"is_corresponding":false},{"id":840009,"name":"Sara Silbert","orcid":"0000-0002-2746-9410","position":7,"is_corresponding":false},{"id":280937,"name":"Haneen Shalabi","orcid":"0000-0001-8692-8034","position":8,"is_corresponding":false},{"id":283310,"name":"Bonnie Yates","orcid":null,"position":9,"is_corresponding":false},{"id":292601,"name":"Jae H. Park","orcid":"0000-0002-2903-5130","position":10,"is_corresponding":false},{"id":278806,"name":"Adam J. Lamble","orcid":"0000-0002-7781-2918","position":11,"is_corresponding":false},{"id":1031829,"name":"Kai Rejeski","orcid":"0000-0003-3905-0251","position":12,"is_corresponding":false},{"id":280941,"name":"Nirali N. Shah","orcid":"0000-0002-8474-9080","position":13,"is_corresponding":false},{"id":1398471,"name":"August A. Culbert","orcid":null,"position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"40953923","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}