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Prophylactic Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Decrease Febrile Neutropenia After Chemotherapy in Children With Cancer: A Meta-Analysis of Randomized Controlled Trials

From the Departments of Pediatrics, Health Policy Management and Evaluation, and Public Health Sciences, University of Toronto; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada; National Cancer Institute, Pediatric Oncology Branch, Rockville, MD; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA; and Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX

Address reprint requests to Lillian Sung, MD, FRCPC, Division of Hematology/Oncology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G 1X8, Canada; e-mail: Lillian.sung{at}sickkids.ca cc: smason{at}childrensoncologygroup.org

PURPOSE: To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality.

METHODS: We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical. From 971 reviewed study articles, 16 were included.

RESULTS: The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%). Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P = .01), and a decrease in hospitalization length, with a weighted mean difference of –1.9 days (95% CI, –2.7 to –1.1 days; P < .00001). CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P = .02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P = .02). There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, –4.3; 95% CI, –10.6 to 2.0 days; P = .2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P = .97).

CONCLUSION: CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.

Supported by fellowships from the Canadian Institutes of Health Research and the Hospital for Sick Children Clinician Scientist Program (L.S.).

This project was a Children's Oncology Group Cancer Control initiative.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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