Aging and haemopoiesis - Implications for treatment with haemopoietic growth factors

Senescence of the lympho-haemopoietic system is associated with an increased incidence of neoplasia, autoimmune diseases and infections. Myelosuppression, either in the context of cancer chemotherapy or in the face of severe infections, commonly manifests as pancytopenia, and has an adverse impact on the prognosis of the elderly cancer patient by increasing infection and bleeding-related morbidity. The physiological basis of this blunted haemopoietic response is unclear, and has been ascribed to age-related deficits in marrow progenitor cell numbers, changes in the marrow microenvironment, decreased production of regulatory growth factors, or a combination of these mechanisms. These age-related deficits tend to be subtle and are only of clinical importance either when present cumulatively or under conditions of extreme haemopoietic stress. Furthermore, some of these deficits can be circumvented with the use of haemopoietic growth factors (HGFs). Thus, the availability in the clinic of various HGFs has had a tremendous impact on the care of the elderly cancer patient. The HGFs currently approved for use are: granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and epoetin-alpha (recombinant human erythropoietin). However, we still need to better elucidate age-related changes in the early stages of haemopoiesis. The question of haemopoietic exhaustion, particularly under prolonged growth factor stimulation, is real and still unanswered.