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.