Acute myeloid leukemia in the elderly: A critical review of therapeutic approaches and appraisal of results of therapy

In the elderly, acute myeloid leukemia (AML) is characterized by a poorer prognosis than in younger patients, due to either host related factors (poor performance status, co-morbid diseases, organ function impairment) or the biology of leukemia itself (high incidence of adverse cytogenetic abnormalities, high frequency of preceding myelodysplastic syndromes, intrinsic resistance to cytotoxic drugs). Current therapeutic results are mostly unsatisfactory and studies reporting high rates of complete remission are probably influenced by selection biases as suggested by the low rate of elderly patients inclusion into cooperative trials. Availability of intensive support including hematopoietic growth factors could stimulate clinicians to manage an increasing number of elderly patients with AML with aggressive programs. However, chemotherapy in the elderly is difficult, costly and usually associated with high morbidity and mortality rate. Therefore, all efforts should be made to identify those subset of elderly patients in whom aggressive treatment may result in a true improvement of disease free and overall survival. The critical analysis of our five years experience, as reported here, seems to suggest that older AML patients displaying unfavourable prognostic factors at diagnosis (i.e., adverse karyotype and high serum LDH levels), but clinically eligible for intensive chemotherapy, do not actually benefit from an aggressive approach. A blind attempt to treat these patients aggressively may be associated with a life threatening toxicity not counterbalanced by an actual survival advantage. We suggest therefore that aggressive treatment should be reserved for elderly AML cases in whom the presence of good prognostic factors at diagnosis predicts that the loss of some patients due to toxicity may be balanced by the achievement of a substantial proportion of long term survivors. Finally, given the biological and clinical heterogeneity of elderly AML patients, a more precise prognostic categorization of these patients would be particularly useful in interpreting future therapeutic results.