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

Abstract

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/m2 (I-MAC) or a high-dose of 36 g/m2 (H-MAC) combined with mitoxantrone. Autologous hematopoietic stem-cell transplantation or intermediate-dose cytarabine (10 g/m2) 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/m2), 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/m2 within first consolidation did not improve treatment outcome.