Real-World Outcomes of Antifungal Prophylaxis in Adult Acute Lymphoblastic Leukemia: A Multicenter Comparison of Fluconazole and Micafungin

Background: Adult acute lymphoblastic leukemia (ALL) patients are at increased risk of invasive fungal infections (IFIs) due to intensive therapy and prolonged neutropenia. While pediatric guidelines support fluconazole or mold-active agents, evidence in adults is limited. This study presents the first multicenter retrospective comparison of fluconazole and micafungin in this setting. Methods: We retrospectively analyzed 336 adult ALL patients from 11 centers in Türkiye (2010–2024) who received fluconazole (n=230) or micafungin (n=106) during induction chemotherapy. IFIs were classified according to EORTC/MSG criteria. Results: The median age was 38.5 years, and 38.7% were female. Proven/probable IFIs occurred in 8.9% of patients, with similar rates between fluconazole and micafungin groups (8.7% vs. 9.4%; p=0.82). Multivariate analysis confirmed no significant association between prophylactic antifungal type and IFI incidence, indicating comparable outcomes across groups. Median prophylaxis duration was longer with fluconazole, while discontinuation rates, switch patterns, and subsequent antifungal use were comparable. Overall infection rates (~60%) and distribution of bacterial, viral, and polymicrobial infections were similar between the two groups. Prior bacterial infection increased IFI risk 2.7-fold, and IFI-positive patients had longer neutropenia. At induction end, remission, refractory, and mortality rates were similar between groups. The median overall survival was 24 months. Conclusion: Fluconazole and micafungin showed similar efficacy as primary antifungal prophylaxis in adult ALL. In accordance with current guidelines, these agents may be preferable to mold-active triazoles, with selection best guided by institutional aspergillosis risk, potential drug–drug interactions, and cost considerations. Prospective randomized trials are warranted to confirm these findings.