INTRODUCTION
Invasive fungal disease (IFD) is a leading cause of mortality in immunocompromised hosts. In children diagnosed with cancer and treated with chemotherapy alone, risk for IFD is augmented by prolonged periods of neutropenia, exposure to specific high-intensity treatment regimens, and systemic corticosteroid use. Risk is also higher among children diagnosed with high-risk acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and relapsed disease.1,2
Among children with hematologic malignancies, the incidence of IFD varies from about 5-10% according to host factors, intensity of the chemotherapy regimen, and historical inconsistencies in supportive care practices.3 Randomized controlled trials conducted in children support the use of mold-active azoles over no systemic antifungal prophylaxis, and over fluconazole prophylaxis in at-risk children undergoing treatment for cancer.4-7 Based on this evidence, national clinical practice guidelines were developed for systemic antifungal prophylaxis in children undergoing treatment for cancer and recipients of hematopoietic stem cell transplant (HSCT).8 Specific recommendations for children with hematologic malignancies not treated with HSCT include administering antifungal prophylaxis to children with AML (strong) and to newly diagnosed or relapsed patients with ALL at high risk for IFD (weak) using a mold-active agent (echinocandin or mold-active azole, strong), particularly during periods of anticipated neutropenia (weak). However, the variability in local fungal organism epidemiology and variation in approaches to leukemia therapy suggest the need for site and protocol-specific adaptation of these guidelines to both facilitate clinical application and minimize risk for IFD.8
We conducted a single-institution retrospective review of children diagnosed with ALL, AML, and lymphoma who developed proven or probable IFD, with a specific focus on invasive mold infections (IMI). Our objective was to assess the IMI incidence and epidemiology pre- and post-implementation of a risk-adapted, local epidemiology-informed algorithm for determining antifungal prophylaxis in children undergoing treatment for hematologic malignancies.