Consensus on the use of neutrophil-stimulating hematopoietic growth factors in clinical practice: an international viewpoint

Hematopoietic growth factors (CSFs) are now available for use in patients with myelosuppression due to congenital, acquired and therapy-induced conditions. Variations in the use of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in different countries are due to differences in approved indications by national regulatory agencies, varying opinions on the importance of certain treatment outcomes, differences in the selection of published and unpublished evidence of efficacy and the impact of the cost of these agents in different health care systems. Through Medline searches and personal files, we have reviewed the published literature on the efficacy and cost of GM-CSF and G-CSF in patients with severe chronic neutropenia and those receiving standard dose chemotherapy or high-dose chemotherapy requiring bone marrow reconstitution. Guidelines were established with regard to (1) the relative merits of different types of clinical studies and (2) the relative importance of different clinical outcomes as reported in these studies. The cost implications of these agents as they apply to the different clinical settings are also reviewed. Recommendations for the use of G-CSF and/or GM-CSF include: (1) the prevention of recurrent, debilitating infections in patients with severe chronic neutropenia; and (2) the maintaining of dose-intensity of potentially curative, standard-dose chemotherapy. While G-CSF and/or GM-CSF have been shown to improve secondary outcomes in higher-than-standard dose-intensive therapy, further studies are needed to test whether such improvements also lead to significant improvements in survival and/or quality of life. These recommendations are based on the collective interpretation of the presented evidence by an international group of investigators in this area.