Future strategies in the control of myelosuppression: the use of colony-stimulating factors.

Recombinant technology has been harnessed to produce sufficient quantities of colony-stimulating factors (CSFs)--also known as hematopoietic growth factors--to make clinical trials with these agents possible. Endogenous CSFs are hormone-like glycoproteins that bind to receptors on target cells and stimulate processes within these cells that mediate their proliferation, maturation, differentiation, and functional activation. Several such CSFs cloned by recombinant DNA technology now are being tested clinically. Some are multilineage growth factors, such as interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), which tend to affect cells early in the hematopoietic hierarchy. Others, such as granulocyte colony-stimulating factor (G-CSF), primarily stimulate the formation of neutrophilic granulocytes. Macrophage CSF predominantly affects monocytes/macrophages. These are late-stage, single-lineage growth factors. Numerous clinical trials with all of these agents are under way. The granulopoietic agents, including GM-CSF and G-CSF, are being tested for their potential use in preventing or ameliorating myelosuppression related to AIDS, antineoplastic chemotherapy, bone marrow transplantation, myelodysplastic syndromes, and aplastic anemia. Clinical trial results on G-CSF and GM-CSF are encouraging thus far. However, it is too early to characterize the effects of IL-3, which is just entering clinical trials.