Meta-analysis: Effect of Prophylactic Hematopoietic Colony-Stimulating Factors on Mortality and Outcomes of Infection

Meta-analysis: Effect of Prophylactic Hematopoietic Colony-Stimulating Factors on Mortality and Outcomes of Infection

Lillian Sung, MD, PhD;
Paul C. Nathan, MD, MSc;
Shabbir M.H. Alibhai, MD, MSc;
George A. Tomlinson, PhD; and
Joseph Beyene, PhD

From the University of Toronto, The Hospital for Sick Children, and University Health Network, Toronto, Ontario, Canada.

Abstract

Background: Benefits of prophylactic hematopoietic colony-stimulating factors (CSFs) in adults and children receiving cancer chemotherapy or undergoing stem-cell transplantation (SCT) are unclear.

Purpose: To determine whether prophylactic CSFs decrease mortality, infections, and febrile neutropenia more than does placebo or no therapy in patients with cancer and in patients undergoing SCT.

Data Sources: Electronic searches of Ovid MEDLINE and EMBASE from inception until April 2007 and of the Cochrane Central Register of Controlled Trials until the second quarter of 2006.

Study Selection: We selected 148 trials that were reported in any language that randomly assigned patients to CSFs or to either placebo or no therapy. Prophylactic CSFs were given concurrently with or after initiation of chemotherapy.

Data Extraction: Two reviewers independently extracted data onto standardized forms.

Data Synthesis: Short-term all-cause mortality appeared to be similar between the prophylactic CSF and the control groups (7.6% vs. 8.0%; relative risk, 0.95 [95% CI, 0.84 to 1.08]; absolute risk reduction, 0.4% [CI, −0.5% to 1.4%]). Risks for infection-related death with CSFs and placebo or no therapy were 3.1% and 3.8%, respectively (relative risk, 0.82 [CI, 0.66 to 1.02]; absolute risk reduction, 0.8% [CI, 0.0% to 1.5%]). Use of CSFs reduced the following more than did placebo or no therapy: documented infections (median rate, 38.9% vs. 43.1%; rate ratio, 0.85 [CI, 0.79 to 0.92]), microbiologically documented infections (median rate, 23.5% vs. 28.6%; rate ratio, 0.86 [CI, 0.77 to 0.96]), and episodes of febrile neutropenia (median rate, 25.3% vs. 44.2%; rate ratio, 0.71 [CI, 0.63 to 0.80]).

Limitations: Trial designs, including assessments of infections, and participants were heterogeneous. Estimates of mortality effects were imprecise.

Conclusions: Prophylactic CSFs may have little or no effect on mortality but do decrease rates of infection in patients receiving cancer chemotherapy or those undergoing SCT.

Article and Author Information

Grant Support: In part by a career development award with the Canadian Child Health Clinician Scientist Training Program, a strategic program with the Canadian Institutes of Health Research (Dr. Sung).
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Lillian Sung, MD, PhD, Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; e-mail, lillian.sung{at}sickkids.ca.
Current Author Addresses: Drs. Sung and Nathan: Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Dr. Alibhai: Toronto General Hospital, Room EN 14-214, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
Dr. Tomlinson: Toronto General Hospital, Eaton Building East, Room 238, 13th Floor, 200 Elizabeth Street, Ontario M5G 2C4, Canada.
Dr. Beyene: Child Health Evaluative Sciences, Research Institute of The Hospital for Sick Children, Room 1206, 123 Edward Street, Toronto, Ontario M5G 1E2, Canada.