University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In the pediatric population, does the use of Granulocyte colony-stimulating factor (G-CSF) decrease the hospital length of stay for fever and neutropenia?

Clinical Bottom Lines

1. In patient with ALL who are admitted with fever and neutropenia the administration of G-CSF in conjunction with antibiotics will decrease the time to resolution of febrile neutropenia by 9 days when compared to antibiotics alone.¹
2. In same group of patients, length of stay from admissions for febrile neutropenia can be reduced by one day (from 5 to 4 days on average) with use of G-CSF in conjunction with antibiotics.
3. There is a decreased risk of developing late-onset fever in patients treated with G-CSF (P=0.08) in conjunction with antibiotic therapy, this effect was seen primarily in patients with severe neutropenia (ie. ANC < 100/mm3).

Summary of Key Evidence

1. 67 pediatric patients admitted for fever and neutropenia were randomized to receive standard antibiotic therapy vs. standard antibiotic therapy plus G-CSF.¹
2. The majority of enrolled patients (59 of 66 patients) were diagnosed with ALL, the remainder had various solid tumors.
3. Enrollment was terminated earlier than planned at the direction of the Children's Oncology Group Date Monitoring Committee because of significant differences between regimens in the two of the study endpoints.
4. The median number of days to resolution of febrile neutropenia was 9 earlier in the antibiotic plus G-CSF group (P<0.0001).
5. Median time to resolution of neutropenia alone was decreased in treatment group however time to resolution of fever alone was similar between the two arms.
6. Median hospitalization days was shortened by 1 day of the G-CSF arm (P<0.04).
7. Decrease in incidence of late-onset fever in the antibiotic plus G-CSF group; the subgroup where this effect was observed were in patients with initial presentation of ANC <100/mcl.
   - Relative risk reduction of 73%, Number Needed to Treat of 6.

Additional Comments

• Demonstrated convincingly that G-CSF decreases duration of febrile neutropenia.
• Patient population sampled - 89% of patients had ALL. Can these results be generalized to the population seen here at UM?
• Study terminated early upon interim analysis which makes interpreting secondary data more difficult. (ie. Hospital length of stay, duration of antibiotic therapy, complications, late-onset fever).
• Appears more studies are needed to clarify if G-CSF should be used routinely in pediatric patients admitted for F&N. It may be that a subgroup of patients (ie. High risk, ANC <100) may benefit the most from treatment.
  

Citation

1. Ozkaynak MF, Krailo M, Chen Z, Feusner J. Randomized comparison of antibiotics with and without granulocyte colony-stimulating factor in chemotherapy-induced febrile neutropenia: A report from the children's oncology group. Pediatr Blood Cancer 2005; 45: 274-280.

CAT Author: Mark C. Zaros, MD

CAT Appraisers: James Gurney, PhD

Date appraised: February 15, 2006