Invasive fungal infections in pediatric leukemia patients receiving fluconazole prophylaxis

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BACKGROUND: Children with acute leukemia have increased risk for invasive fungal infections (IFI) but the role of long term antifungal prophylaxis (AFP) in morbidity and mortality of IFI is not well-known. PROCEDURE: Medical records of 154 children with acute leukemia who received AFP with fluconazole during intensive chemotherapy were retrospectively reviewed to determine risk factors, clinical characteristics and outcome of IFI. RESULTS: The overall incidence of IFI was 13.6%. Frequencies of proven, probable and possible infections were 7.2%, 2.6%, and 3.8%, respectively. The causative agent was Candida in 12 (57.2%) and Aspergillus in 9 (42.8%) children. There were 10 children with candidemia (47.6%), 7 with pulmonary aspergillosis (33.4%), 2 with hepatosplenic candidiasis (10.0%), one with sinopulmonary aspergillosis (4.5%) and one with sinus aspergillosis (4.5%). IFI was twice as common in acute myeloid leukemia (AML) (20.7%) than in acute lymphoblastic leukemia (ALL) (10.2%). Duration of profound neutropenia (P = 0.01) and steroid medications (P = 0.001) were significantly associated with IFI in univariate but not in multivariate analysis. Liposomal amphotericin B (L-AMB) was successful in 15 of 21 children as a single agent. Voriconazole produced complete response in four children with invasive aspergillosis and two with hepatosplenic candidiasis, who were unresponsive to L-AMB. The rate of IFI attributable death was 5%. CONCLUSIONS: Our results indicate that AFP with fluconazole and early empirical antifungal therapy may be effective in reducing the incidence and mortality of IFI in children with acute leukemia.