AGING AND HEMATOPOIESIS - IMPLICATIONS FOR TREATMENT WITH HEMATOPOIETIC GROWTH-FACTORS

Senescence of the lympho-haemopoietic system is associated with an inc reased incidence of neoplasia, autoimmune diseases and infections. Mye losuppression, 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 i ncreasing infection and bleeding-related morbidity. The physiological basis of this blunted haemopoietic response is unclear, and has been a scribed to age-related deficits in marrow progenitor cell numbers, cha nges in the marrow microenvironment, decreased production of regulator y growth factors, or a combination of these mechanisms. These age-rela ted deficits tend to be subtle and are only of clinical importance eit her when present cumulatively or under conditions of extreme haemopoie tic stress. Furthermore, some of these deficits can be circumvented wi th the use of haemopoietic growth factors (HGFs). Thus, the availabili ty in the clinic of various HGFs has had a tremendous impact on the ca re of the elderly cancer patient. The HGFs currently approved for use are: granulocyte colony-stimulating factor, granulocyte-macrophage col ony-stimulating factor and epoetin-alpha (recombinant human erythropoi etin). However, we still need to better elucidate age-related changes in the early stages of haemopoiesis. The question of haemopoietic exha ustion, particularly under prolonged growth factor stimulation, is rea l and still unanswered.