Invasive fungal disease in children with acute myeloid leukaemia: An Australian multicentre 10-year review.

Background: Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML.

Methods: As part of the retrospective multicentre cohort TERIFIC (The Epidemiology and Risk factors for Invasive Fungal Infections in immunocompromised Children) study, proven/probable/possible IFD episodes occurring in children with primary or relapsed/refractory AML from 2003 to 2014 were analysed. Crude IFD prevalence, clinical characteristics, microbiology and treatment were assessed. Kaplan-Meier survival analysis was used to estimate 6-month survival.

Results: There were 66 IFD episodes diagnosed in 63 children with AML. The majority (75.8%) of episodes occurred in the context of primary AML therapy. During primary AML therapy, the overall prevalence was 20.7% (95% CI 15.7%-26.5%) for proven/probable/possible IFD and 10.3% (95% CI 6.7%-15.0%) for proven/probable IFD. Of primary AML patients, 8.2% had IFD diagnosed during the first cycle of chemotherapy. Amongst pathogens implicated in proven/probable IFD episodes, 74.4% were moulds, over a third (37.9%) of which were non-Aspergillus spp. Antifungal prophylaxis preceded 89.4% of IFD episodes, most commonly using fluconazole (50% of IFD episodes). All-cause mortality at 6 months from IFD diagnosis was 16.7% with IFD-related mortality of 7.6% (all in cases of proven IFD).

Conclusions: IFD is a common and serious complication during paediatric AML therapy. Mould infections, including non-Aspergillus spp. predominated in this cohort. A systematic approach to the identification of patients at risk, and a targeted prevention strategy for IFD is needed.