Abstract
Patients with leukemia are at heightened risk for invasive fungal infections (IFIs) due to profound immunosuppression caused by both the malignancy and its treatment. Chemotherapy-induced neutropenia, mucosal barrier disruption, and impaired innate and adaptive immune responses create a highly permissive environment for opportunistic fungal pathogens. Antifungal prophylaxis, particularly in acute myeloid leukemia (AML), has become a cornerstone in reducing IFI-related morbidity and mortality. This review outlines the immunopathogenic mechanisms underlying susceptibility to IFI and discusses current evidence on the optimal timing and therapeutic strategies for antifungal intervention. The clinical utility of key antifungal agents, namely, posaconazole, isavuconazole, and voriconazole, is critically evaluated. We also examine the potential role of emerging agents such as opelconazole, which enables targeted pulmonary delivery and prolonged epithelial retention, representing a promising approach to IFI prevention. Drug-specific considerations, including pharmacokinetics, drug-drug interactions, toxicity profiles, and cost-effectiveness, are analyzed in the context of clinical decision-making. Finally, we emphasize the importance of tailoring antifungal strategies based on leukemia subtype, immunosuppressive status, and individual patient factors to optimize outcomes and support antifungal stewardship in hematologic malignancies.