Invasive fungal infections in pediatric leukemia patients receiving fluconazole prophylaxis

Abstract

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. 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. 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%. 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.