Aging and the hemopoietic system

While increasing numbers of elderly patients are expected to require chemotherapy and/or radiotherapy in the future, the application of standard-dose chemotherapy in unselected cohorts of older patients usually results in a higher rate of life-threatening myelosuppression and treatment-related deaths compared to young individuals treated with the same chemotherapy regimens. The biologic mechanisms underlying reduced tolerance to chemotherapy of the hemopoietic system in older individuals are still poorly understood. Unveiling such mechanisms therefore represents a fundamental issue to ameliorate chemotherapy strategies for older cancer patients. Current evidence suggests that aging-related bone marrow changes are rather subtle and most probably irrelevant for the hemopoietic function of normal older individuals. These changes, however, may become clinically evident under conditions of severe hemopoietic stress such as the administration of repeated courses of chemo-radiotherapy. The mechanisms underlying age-dependent decline in the hematopoietic reserve are not fully clarified and probably involve age-associated changes in the stem and progenitor cells compartments which may ultimately lead to a reduced ability of recovery from hematologic stress. Age-related changes in endogenous anti-tumor immune responses also need to be accounted for in the aim of managing residual disease in elderly cancer patients treated with effective chemo-radiotherapy. Since dendritic cells (DCs) generated from older individuals appear fully functional, dendritic cell-based immunotherapy may represent an important tool to treat residual disease in aged cancer patients. While it is clearly established that primary prophylaxis with hemopoietic growth factors currently enables a large fraction of older cancer patients to receive appropriate chemotherapy, innovative strategies in the use of such growth factors may allow time-intensification of standard-dose chemotherapy for treating chemosensitive tumors, i.e. non-Hodgkin's lymphomas (NHLs), occurring in older individuals.