Breakthrough Invasive Fungal Infections in Pediatric Acute Myeloid and Lymphoblastic Leukemia Receiving Mold-active Prophylaxis.
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BACKGROUND: Breakthrough invasive fungal infections (IFIs) remain a major challenge in children with acute leukemia, even under mold-active prophylaxis. Data on the epidemiology, risk factors and outcomes of breakthrough IFIs in pediatric populations are limited. METHODS: This study included patients 0-18 years of age with acute leukemia who were diagnosed and followed at the Pediatric Hematology Clinic of Ankara Bilkent City Hospital between February 2019 and December 2023. We conducted a retrospective cohort study of 147 pediatric patients with acute leukemia who received mold-active antifungal prophylaxis. Demographic and clinical features, antifungal prophylactic regimens, infection classifications (proven, probable and possible), microbiological and radiological findings and outcomes were analyzed. IFIs were defined and classified according to the EORTC/MSGERC 2020 criteria. RESULTS: Among 147 patients (43.5% female, 56.5% male; mean age 9.5 years), 68.0% had acute lymphoblastic leukemia and 32.0% had acute myeloid leukemia. All patients received mold-active prophylaxis, most commonly voriconazole (84.4%, n = 124). Overall, 29.3% (n = 43) of patients developed an IFI. Among those with IFI, 81.4% (n = 35) were classified as possible, 11.6% (n = 5) as probable and 7.0% (n = 3) as proven. Infection incidence was similar between acute lymphoblastic leukemia (29.0%) and acute myeloid leukemia (31.2%) (P = 0.779). A total of 7 patients died because of the fungal infections, yielding a case-fatality rate of 16.3% (7/43) among patients with IFI. Mortality varied markedly by diagnostic certainty: 5.7% in possible, 60.0% in probable and 66.7% in proven IFIs. Proven/probable infections were mainly due to Aspergillus spp. The most frequently used therapeutic agents were liposomal amphotericin B (43.2%) and caspofungin (30.9%), alone or in combination. CONCLUSION: Despite mold-active antifungal prophylaxis, nearly one-third of pediatric leukemia patients developed IFIs, with high mortality in probable and proven cases. The predominance of breakthrough mold infections underscores the limitations of current prophylactic strategies. Optimized prophylaxis, therapeutic drug monitoring and early diagnostic approaches are urgently needed to reduce the burden of IFIs in this high-risk population.