Wan, L., Zhang, Y., Lai, Y., Jiang, M., Song, Y., Zhou, J., . . . Wang, C. (2015). Effect of granulocyte-macrophage colony-stimulating factor on prevention and treatment of invasive fungal disease in recipients of allogeneic stem-cell transplantation: A prospective multicenter randomized phase IV trial. Journal of Clinical Oncology, 33, 3999–4006. 

To test the hypothesis that prophylactic granulocyte macrophage–colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD) in patients with neutropenia receiving allogeneic hematopoietic cell transplantation (HCT)

Patients were randomly assigned to receive GM-CSF, GCSF, or a combination of GM-CSF and GCSF. Administration was begun on day 5 after transplantation and continued until neutrophil recovery (ANC > 1.5 x 10⁹ for two days). If ANC declined within five days after stopping the CSF, CSF was resumed until neutrophil recovery again. All received antibiotic prophylaxis with levofloxacin and antifungal prophylaxis with oral fluconazole. Patients were followed for the study for 100 days post transplantation.

• N = 183   
• MEAN AGE = 31.76 years
• AGE RANGE = 13–60 years
• MALES: 72.1%, FEMALES: 27.9%

• SITE: Multi-site    
• LOCATION: China

PHASE OF CARE: Transition phase after active treatment

• Randomized, prospective, open-label, three-group trial

• IFD was determined as proven, probable, or possible according to the European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases (NIAID) Myoses Study Group (MSG)
• Invasive Aspergillus was diagnosed according to the Infectious Diseases of Society of America's guidelines

No significant differences existed between groups in the prevalence of proven and probable IFD from molds or yeasts overall. In the G-CSF only group, 11.6% had IFD attributable death, compared to one patient in each of the other study groups (p = 0.008). In multivariate analysis to include potential confounders, risk of death was 4.496 times higher (95% confidence interval [CI] [2.5, 8.1]) in patients with proven or probable IFD compared to those without IFD. Those receiving only G-CSF had a significantly higher 100-day mortality rate (p = 0.037). All infection-related mortality was lowest in the GM-CSF group (p = 0.011).

The findings showed that GM-CSF was more effective than G-CSF in the prevention of infection, fungal disease, and infection-related mortality at 100 days in patients undergoing allogeneic hematopoietic cell transplantation (HCT).

• Risk of bias (no blinding)

This study suggests that the use of GM-CSF versus G-CSF is more effective for infection prevention in patients undergoing allogeneic HCT with neutropenia. The effective use of colony-stimulating factors has been shown to reduce infection and IFD-related mortality in at-risk patients.