Prevalence and mortality of infections following CAR T-cell therapy in children, adolescents, and young adults: A systematic review and meta-analysis

Abstract

Abstract Introduction: Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of children, adolescents, and young adults (CAYA) with relapsed or refractory acute lymphoblastic leukemia (ALL). However, the burden of infectious complications in this population remains unclear. We conducted this analysis to assess the prevalence and characteristics of infections following CAR T-cell therapy in CAYA patients. Methods: Following PRISMA guidelines and the Cochrane Handbook, we conducted a comprehensive literature search in PubMed, Scopus, Web of Science, and Cochrane Library from inception to June 2025 for studies reporting infection rates in CAYA patients (≤26 years) receiving CAR T-cell therapy. Three independent reviewers screened the retrieved records for eligibility, and three reviewers independently extracted data from the included studies. Any discrepancies during screening or extraction were resolved through consensus discussion. Pooled estimates were calculated using R software. Denominators vary by outcome due to variable reporting across studies. Results: Our search yielded 5,889 studies, of which 13 met our inclusion criteria, comprising a total of 582 patients. The median age of included patients was 11 years (range: 1–26). Most patients (n=573, 98.45%) had ALL. Any-grade infections occurred in 227 out of 558 patients (41%, 95% CI: 0.29–0.53; I² = 86.5%; p < 0.0001), reported over a median duration of 90 days (range: 30–438 days) following CAR T-cell therapy. Severe infections (grade ≥3) developed in 57 out of 285 patients (22%, 95% CI: 0.13–0.34; I² = 74.7%; p = 0.0003). The infection-related mortality rate across all studies was 3% (95% CI: 0.01–0.06; I² = 58.3%; p = 0.0042). A total of 113 bacterial infection events were reported among 362 patients, 66 viral infection events among 398 patients, and 16 fungal infection events among 453 patients. The majority of infections were due to bacteremia, followed by respiratory tract infections. Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis were the most frequently reported bacterial pathogens. For viral infections, rhinovirus/enterovirus predominated. Conclusion: Infections are a frequent and serious complication following CAR T-cell therapy in CAYA patients. Targeted efforts to prevent and manage their risks are critical to improve survival in this high-risk group.