Revisiting invasive fungal infections in acute lymphoblastic leukemia: a systematic review and meta-analysis

Invasive fungal infections (IFIs) cause substantial morbidity and mortality, yet optimal antifungal prophylaxis in adult acute lymphoblastic leukemia (ALL) remains uncertain given unclear incidence and drug interaction constraints. We performed a PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO CRD420251048884) of PubMed, Embase, and Cochrane CENTRAL from inception through September 2025, including adults with ALL receiving antineoplastic therapy, excluding HSCT and pediatric cohorts. Primary outcome was IFI incidence per European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria; invasive aspergillosis (IA) was secondary. Of 1,789 records, 36 studies met eligibility; 23 contributed to meta-analyses. Pooled incidence of proven/probable IFI was 9% (95% CI 7-11%; N = 3,316), proven/probable/possible IFI 16% (12-21%; N = 806), and IA 5% (4-8%; N = 3,190). IFIs remain clinically significant in adult ALL, supporting risk-adapted prophylaxis during higher-risk treatment phases. Heterogeneity reflected differences in prophylaxis, treatment, and limited comparative data on strategies across studies.