Intensified double induction therapy with high dose mitoxantrone, etoposide, m-amsacrine and high dose ara-C for elderly acute myeloid leukemia patients aged 61-65 years

Abstract

BACKGROUND AND OBJECTIVES: Treatment outcome in elderly patients with acute myeloid leukemia (AML) is still disappointing. However, some trials showed that increasing the dosage of anthracyclines within induction therapy improved treatment outcome substantially. We, therefore, tried to escalate induction therapy further in a group of young elderly AML patients. DESIGN AND METHODS: In a multicenter trial 33 patients aged 61-65 years with de novo or secondary AML were treated with double induction therapy including high dose mitoxantrone, etoposide and ara-C (MAV) in the first course and m-amsacrine together with high dose ara-C (MAMAC) in the second course. Treatment results were compared to those in 39 AML patients older than 65 years receiving conventional double induction therapy including daunorubicin and ara-C (DA I and DA II) within the same time period. RESULTS: Compared to results achieved with conventional induction therapy, intensified double induction therapy did not significantly improve CR rates, overall or disease-free survival. Hematologic toxicity was not different between the two groups, but non-hematologic toxicity was significantly higher with MAV/MAMAC. This was mainly due to gastro-intestinal or liver toxicity. The rate of early mortality (death within the first 12 weeks) was 42% in the group receiving intensified therapy and 18% in that given conventional induction therapy (p=0.04). INTERPRETATION AND CONCLUSION: Intensification of double induction therapy using high dose mitoxantrone and high dose ara-C in AML patients aged 61-65 years did not lead to improved treatment outcome and conferred an unacceptable early death rate due to high non-hematologic toxicity. Risk-adapted or alternative treatment strategies are needed to improve treatment outcome in these young elderly AML patients.