Risk factors associated with invasive fungal disease in children with cancer and febrile neutropenia: a prospective multicenter evaluation.

Background: Empiric antifungal treatment has become standard of care in children with cancer and prolonged fever and febrile neutropenia (FN), with the downside that it leads to significant over treatment. We characterized epidemiologic, clinical, and laboratory features of invasive fungal disease (IFD) in children with cancer and FN with the aim to identify risk factors for IFD that can aid in better selecting children who require antifungal treatment. Methods: In a prospective, multicenter study, children admitted with FN at high-risk for sepsis, in 6 hospitals in Santiago, Chile were monitored from admission until the end of the FN episode. Monitoring included periodic evaluation of clinical findings, absolute neutrophil count, absolute monocyte count (AMC), serum C-reactive protein (CRP), bacterial cultures, imaging studies, and galactomannan antigen. A diagnosis of proven, probable, and possible IFD was made after episode resolution based on European Organization for Research and Treatment of Cancer classification. Results: A total of 646 high-risk FN episodes were admitted during the study period, of which 604 were enrolled. IFD was diagnosed in 35 episodes (5.8%) of which 7 (1.2%) were proven, 10 (1.6%) probable, and 18 (3.0%) possible. Four variables obtained on day 4 were significantly more common in IFD cases, which were presence of fever, absolute neutrophil count <= 500/mm(3), AMC <= 100/mm(3), and CRP >= 90 mg/L. The combination of fever, AMC <= 100/mm(3), and CRP >= 90 at day 4 provided a RR for IFD of 5.4 (99% CI, 3.2-9.2) with a sensitivity of 75%, specificity of 87%, positive and negative predictive values of 13% and 99%, respectively. Conclusions: Fever persisting at day 4 of admission, together with AMC <= 100 and CRP >= 90 significantly increased the risk for IFD in children with cancer.