Rapid Remission Induction and Improved Disease Free Survival in Acute Myeloid Leukaemia Using Daunorubicin, ARA-C, and CCNU

Abstract

Thirty-four patients with acute myeloblastic leukaemia were treated with DAC, a schedule containing the nitrosourea CCNU (lomustine) 200 mg/m2 given on day one of treatment, together with a standard "3 + 7" remission induction schedule of daunorubicin (DR) and cytosine arabinoside (Ara-C). The results were compared with an historical control group of 24 patients who received 3 + 7 remission induction (DA). The DAC patients were older (median age 55 years) compared with the DA patients (median age 42 years), and had a higher frequency of poor prognosis features including secondary AML and prior myelodysplasia (11/34 DAC patients versus 1/24 patients receiving DA). Overall remission induction was the same for both groups (79%), but 89% of DAC patients who achieved remission did so with one course, compared with 37% of DA patients. The cytopenic phase following a single course of DAC was only slightly longer than that of a single course of DA (26 days vs. 19.5 days). DAC also gave a higher three year actuarial survival than DA (34% vs. 11%), and a lower relapse probability (44% vs. 74%). These results support the hypothesis that chemotherapy for AML may be favoured by including agents such as CCNU, which are active against both non-cycling and cycling leukaemic stem cells, in remission induction schedules.

Keywords: Ara-C; CCNU; Remission induction; acute myeloid leukaemia; daunomycin; survival.