Acute myeloid leukemia: treatment of adults under 60 years

Current chemotherapy with advanced supportive care will enable 75-80% of acute myeloid leukemia patients aged 60 years or under to enter complete remission. Several regimens achieve broadly similar results. For patients who enter complete remission, the overall relapse risk is now 45-50%, but this is highly variable and is primarily determined by the biology of the disease. Cytogenetics are strongly influential in response to induction and consolidation with t(15:17), t(8:21) and inv(16) either occurring alone or with additional abnormalities having a relapse risk of about 30% and complex changes, abnormal 3q or abnormalities of chromosomes 5 and 7 resulting in a lower remission rate and a rapid relapse cumulating to 80%. FLT3 mutations occur in 25% of patients and are an independent predictor of relapse and, when combined with cytogenetics, adversely influence the prognosis in each cytogenetic risk group. Recent prospective collaborative group trials have endeavored to evaluate allogeneic and autologous bone marrow transplant against or in addition to consolidation chemotherapy. Suboptimal treatment delivery emerged as a problem. When the results were reported on an intention-to-treat basis, no overall survival advantage was consistently seen for either type of transplant. However, a significant reduction in risk of relapse was usually seen overall and within risk groups. Analysis within risk groups suggests that transplant is not indicated in good risk disease and continues to require evaluation in standard or poor risk patients. It is probable that traditional dose intensification has now reached its limits of tolerability, so new approaches will be required for further progress to be made. Modulation of chemoresistance mechanisms or immunologically directed chemotherapy represent immediate prospects for clinical study.