Cytarabine Dose of 36 g/m2 Compared With 12 g/m2 Within First Consolidation in Acute Myeloid Leukemia: Results of Patients Enrolled Onto the Prospective Randomized AML96 Study

Purpose To assess the optimal cumulative dose of cytarabine for treatment of young adults with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1996 and 2003, 933 patients (median age, 47 years; range 15 to 60 years) with untreated AML were randomly assigned at diagnosis to receive cytarabine within the first consolidation therapy at either a intermediate-dose of 12 g/m(2) (I-MAC) or a high-dose of 36 g/m(2) (H-MAC) combined with mitoxantrone. Autologous hematopoietic stem-cell transplantation or intermediate-dose cytarabine (10 g/m(2)) were offered as second consolidation. Patients with a matched donor could receive an allogeneic transplantation in a risk-adapted manner. Results After double induction therapy including intermediate-dose cytarabine (10 g/m(2)), mitoxantrone, etoposide, and amsacrine, complete remission was achieved in 66% of patients. In the primary efficacy analysis population, a consolidation with either I-MAC or H-MAC did not result in significant differences in the 5-year overall (30% v 33%; P = .77) or disease-free survival (37% v 38%; P = .86) according to the intention-to-treat analysis. Besides a prolongation of neutropenia and higher transfusion demands in the H-MAC arm, rates of serious adverse events were comparable in the two groups. Conclusion In young adults with AML receiving intermediate-dose cytarabine induction, intensification of the cytarabine dose beyond 12 g/m(2) within first consolidation did not improve treatment outcome. J Clin Oncol 29:2696-2702. (C) 2011 by American Society of Clinical Oncology