Randomized comparison of antibiotics with and without granulocyte colony-stimulating factor in children with chemotherapy-induced febrile neutropenia: A report from the Children's Oncology Group

Abstract

Purpose To determine if granulocyte colony‐stimulating factor (G‐CSF) with empirical antibiotics accelerates febrile neutropenia resolution compared with antibiotics without it. Patients and Methods Eligible children were treated without prophylactic G‐CSF and presented with fever (temperature >38.3°C) and neutropenia afterward. Patients with acute myelogenous leukemia and myelodysplastic syndrome were excluded. Assignments were randomized between G‐CSF (5 μg/kg/day) or none beginning within 24 hr of antibiotics. Subcutaneous administration was recommended, but intravenous G‐CSF was allowed. Patients remained on study until absolute neutrophil count (ANC) >500/μl and ≥48 hr without fever. Results One of 67 patients enrolled was ineligible, 59 had acute lymphoblastic leukemia (ALL). Thirty‐four were assigned to antibiotics, 32 to G‐CSF plus antibiotics. Adding G‐CSF significantly reduced neutropenia and febrile neutropenia recovery times. Median days to febrile neutropenia resolution was nine earlier with G‐CSF (4 vs. 13 days) (P < 0.0001). However, there was no difference in the resolution of fever between arms. Hospitalization median was shorter by 1 day with G‐CSF (4 vs. 5 days) (P = 0.04). There was no difference in the duration of IV and oral antibiotic treatment, addition of antifungal therapy, and shock incidence. A trend for decreased incidence of late fever with G‐CSF was noted (6.3 vs. 23.5%) (P = 0.08). Conclusions Adding G‐CSF to empiric antibiotic coverage accelerates chemotherapy‐induced febrile neutropenia resolution by 9 days in pediatric patients, mainly with ALL, which results in a small but significant difference in the median length of hospitalization.