Hematopoietic growth factors

Erythropoietin is a lineage-specific distal-acting factor that stimulates maturation of committed erythroid progenitors to become mature erythrocytes.3 Carbohydrates, rich in sialic acid, make up 30% to 40% of the 34,000-Da molecule and are essential for its secretion, stability in the circulation, and biologic activity. Many earlier-acting factors, including stem cell factor/kit ligand, interleukin (IL)-11, IL-3, granulocyte colony-stimulating factor (G-CSF), and IL-6, all interact in the development of erythroid progenitor cells (burst-forming unit erythroid) from the quiescent stem cell. Granulocytemacrophage colony-stimulating factor (GM-CSF) and IL-3 are important factors in the differentiation of burst-forming unit erythroid to the more mature colony-forming unit erythroid. However, in this cascade of hematopoietic growth factors, erythropoietin is the critical hormone regulating final red cell production from the stage of the colony-forming unit erythroid to the basophilic erythroblast and ultimately to the erythrocyte. In humans, erythropoietin levels remain relatively constant until the hemoglobin level falls below 12 g per dl, at which time plasma erythropoietin levels increase4 (Fig. 6.1). This observation suggests that rising erythropoietin levels may be a physiologic response to tissue hypoxia at hemoglobin Hematopoietic growth factors are glycoproteins that stimulate the proliferation and development of clonogenic precursor cell populations. Through recombinant technology, hematopoietic growth factors administered at pharmacologic doses can provide significant clinical benefit for the cancer patient undergoing chemotherapy. Anemia can be reversed with the use of recombinant erythroid stimulating agents (ESAs) reducing transfusions and improving anemia-related symptoms such as fatigue. Neutropenia and its complications can be ameliorated by the use of myeloid growth factors (MGFs). These MGFs have also had a major role in the development of the technology of peripheral blood progenitor cell mobilization, reducing prolonged cytopenias after high-dose chemotherapy. Thrombopoietic agents have shown promising activity improving platelet counts in patients with immune thrombocytopenia (ITP), and studies in cancer chemotherapy patients are underway. Much has been written and reviewed about the hematopoietic growth factors in terms of their biology and clinical application. This chapter summarizes the practicing oncologist areas in which hematopoietic growth factors have been demonstrated to be of clinical benefit, where they have not been shown to be beneficial, or potentially harmful, and where questions remain about the best use of these biologic agents in the supportive care of cancer patients.