Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL Journal Article
| Authors: | Culbert, A. A.; Gava, F.; Valtis, Y. K.; Satta, T.; Vora, S.; Rocco, J. M.; Nussenblatt, V.; Silbert, S. K.; Shalabi, H.; Yates, B.; Park, J. H.; Lamble, A. J.; Rejeski, K.; Shah, N. N. |
| Article Title: | Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL |
| Abstract: | <p>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/mu L 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:<bold> </bold>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.</p> |
| Keywords: | leukemia; infection; cytopenia; chimeric antigen receptor - car |
| Journal Title: | Journal for ImmunoTherapy of Cancer |
| Volume: | 13 |
| Issue: | 9 |
| ISSN: | 2051-1426 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2025-09-14 |
| Start Page: | e012436 |
| Language: | English |
| ACCESSION: | WOS:001572409900001 |
| DOI: | 10.1136/jitc-2025-012436 |
| PROVIDER: | wos |
| PMCID: | PMC12434746 |
| PUBMED: | 40953923 |
| Notes: | Article -- Source: Wos |
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