HIGH-DOSE CHEMOTHERAPY IN ADULT ACUTE MYELOID-LEUKEMIA - RATIONALE AND RESULTS

Preclinical studies and retrospective evaluations of clinical trials o f a number of cytotoxic drugs have provided a rationale for the use of high doses of chemotherapy in adults with acute myeloid leukemia (AML ). To maximize cure and remission rates at an acceptable cost in toxic ity, many schedules and combinations of dose-intensive chemotherapy ha ve been tested in recent years in patients with de novo disease, cytos ine arabinoside (Ara-C) being the most extensively evaluated drug. In this article we review the principal results of both randomized and no n-controlled studies. Our analysis indicates that high-dose Ara-C (HID AC) used during induction results is no substantial benefit relative t o conventional doses of drug. On the other hand, consolidation with HI DAC is a major advance in the treatment of this disease. In fact, in i ndividuals less than 60 years of age and a favorable or intermediate-r isk karyotype, HIDAC-based regimens have resulted in survival estimate s comparable to those of autologous or allogeneic bone marrow transpla ntation. Yet, the role of HIDAC is irrelevant in younger individuals w ith an unfavorable cytogenetic pattern and detrimental in patients gre ater than 60 years of age. Since recently new cytotoxic agents have ex panded the armamentarium of antileukemic drugs, well conducted randomi zed trials of dose intensive chemotherapy still need to be performed t o optimize schedules and combinations of drugs in patients with AML. C opyright (C) 1996 Elsevier Science Ltd.