Hematopoiesis is an intricate, well-regulated, and homeostatic multistep process that allows immature precursor cells in the bone marrow to proliferate, differentiate, mature, and become functional blood cells that transport oxygen and carbon dioxide; contribute to host immunity; and facilitate blood clotting. In the early 1900s, scientists recognized the presence of circulating factors that regulate hematopoiesis. Scientific progress was slow until it became possible to purify sufficient quantities to evaluate the characteristics and biologic potential of the isolated materials. The introduction of recombinant DNA technology triggered a flurry of studies and an information explosion, which confirmed hematopoiesis is mediated by a series of hematopoietic growth factors (HGF) that acts individually and in various combinations involving complex feedback mechanisms. Today, many HGF have been isolated; some have been studied extensively, and a few have been manufactured for clinical use. In this chapter, the HGF molecular structure and mechanism of action, its main pharmacokinetic and pharmacodynamic properties, as well as the clinical indications and main toxicities are described.
KeywordsHematopoietic growth factors Erythropoietin Granulocyte colony-stimulating factor (G-CSF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Stem cell factor (SCF) Thrombopoietin (TPO)
Parts of this chapter are updated versions of previously published portions of several other chapters and/or review manuscripts, that include:
Heatherington AC (2003) Clinical pharmacokinetic properties of rHuEPO: a review. In: Molineux G, Foote MA, Elliott S (eds) Erythropoietins and erythropoiesis: molecular, cellular, preclinical, and clinical biology. Birkhauser, Basel, pp 87–112
Elliot S, Heatherington AC, Foote MA (2004) Erythropoietic factors: clinical pharmacology and pharmacokinetics. In: Morstyn G, Foote MA, and Lieschke GJ (eds) Hematopoietic growths factors in oncology. Humana Press, Totowa, pp 97–123
Foote AN (2008) Hematopoietic growth factors. In: Crommelin DJA, Sindelar RD, Meibohm B (eds) Pharmaceutical biotechnology. Fundamentals and applications, 3rd edn. Informa Healthcare USA, New York, pp 225–242
Doshi S, Perez-Ruixo JJ, Jang GR, Chow A, Elliot S (2008) Pharmacocinétique de les agents stimulant l’érythropoïèse. In: Rossert J, Casadevall N, Gisselbrecht C (eds) Les agents stimulant l’érythropoïèse. Paris, France
Doshi S, Perez-Ruixo JJ, Jang GR, Chow AT (2009) Pharmacokinetics of erythropoiesis-stimulating agents. In: Molineux G, Foote MA, Elliott S (eds) Erythropoietins and erythropoiesis: molecular, cellular, preclinical, and clinical biology. 2nd edn. Birkhäuser Verlag AG, Basel, pp 195–224.
Doshi S, Krzyzanski W, Yue S, Elliott S, Chow A, Pérez-Ruixo JJ. Clinical pharmacokinetics and pharmacodynamics of erythropoiesis-stimulating agents. Clin Pharmacokinet. 2013 Dec;52(12):1063-83.
- Aapro MS, Bohlius J, Cameron DA et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47:8–32CrossRefGoogle Scholar
- Chapel S, Veng-Pedersen P, Hohl RJ, Schmidt RL, McGuire EM, Widness JA (2001) Changes in erythropoietin pharmacokinetics following busulfan-induced bone marrow ablation in sheep: evidence for bone marrow as a major erythropoietin elimination pathway. J Pharmacol Exp Ther 298:820–824PubMedGoogle Scholar
- Glaspy J, Henry D, Patel R et al (2005) The effects of chemotherapy on endogenous erythropoietin levels and the pharmacokinetics and erythropoietic response of darbepoetin alfa: a randomised clinical trial of synchronous versus asynchronous dosing of darbepoetin alfa. Eur J Cancer 41:1140–1149CrossRefGoogle Scholar
- Heatherington AC (2003) Clinical pharmacokinetic properties of rHuEPO: a review. In: Molineux G, Foote MA, Elliott S (eds) Erythropoietins and erythropoiesis: molecular, cellular, preclinical, and clinical biology. Birkhauser, Basel, pp 87–112Google Scholar
- Kuter DJ, Hunt P, Sheridan W, Zucker-Franklin D (eds) (1997) Thrombopoiesis and thrombopoeitin. Humana Press Inc, Totowa, p 412Google Scholar