Infections Following CAR-T therapies in Children, Adolescents, and Young Adults: A Systematic Review and Meta-Analysis

• In patients aged ≤26 years, the pooled prevalence of infection following CAR-T was 39%, with 20% being severe. • In patients aged ≤26 years treated with CAR T-cell therapy, bacterial infections were most common, whereas fungal infections were rare. Chimeric antigen receptor (CAR) T-cell therapy has transformed care for children, adolescents, and young adults (CAYA; age ≤26 years) with relapsed or refractory hematological malignancies. However, the burden of infectious complications in this population is poorly defined, with most data derived from adult cohorts. We conducted a systematic review and meta-analysis to assess the prevalence of infections following CAR T-cell therapy in CAYA patients. We searched PubMed, Scopus, Web of Science, and Cochrane Library through June 17, 2025, for studies reporting infection rates in CAYA patients receiving CAR T-cell therapy. Random-effects models were used to pool the prevalence of all-grade infections (primary outcome), severe (grade ≥3) infections, infection-related mortality, and infections by etiology (bacterial, viral, fungal) and timing (early ≤28–30 days vs late >28–30 days). Twelve studies (567 patients; 98.4% with B- acute lymphoblastic leukemia (B-ALL); median age 11 years) were included. The pooled prevalence of all-grade infections was 39% (95%CI: 27–51%) over a median reporting period of 90 days. Pooled prevalence of severe (grade ≥3) infections was 20% (95%CI: 11–31%), and infection-related mortality was 2% (95%CI: 0–4%). During the early period (≤28–30 days), bacterial infections prevalence was 14% of all patients who received CAR-T cell therapy, viral infections was 13%, and fungal infections was 2%. In Conclusion, infections are frequent following CAR T-cell therapy in CAYA patients. Bacterial infections are most common, followed by viral infections, while fungal infections are rare. These findings emphasize the importance of tailored prophylactic strategies to improve outcomes in this population.