Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used in healthy donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. The spectrum of its biologic and molecular activities in healthy individuals is coming into sharper focus, creating a unique set of challenges and clarifying the need to monitor and safeguard donor safety. Accumulating evidence indicates that rhG-CSF effects are not limited to the myeloid cell lineage. This may reflect the presence of functional G-CSF receptors on other cell types and tissues, as well as rhG-CSF-induced modulation of cytokine networks. While most rhG-CSF-induced effects are transient and self-limiting, preliminary, provocative data have suggested the possibility of a more durable effect on the chromosomal integrity of lymphocytes. While these reports have not been validated and have been subject to criticism, they are prompting prospective studies and monitoring efforts to determine whether there is a significant risk of long-term adverse events (eg, hematologic malignancies) in healthy PBPC and granulocyte donors. Based on the totality of information that is currently available, the administration of rhG-CSF to healthy donors for the purpose of PBPC donation continues to have a favorable risk-benefit profile.