THE INFLUENCE OF INDUCTION CHEMOTHERAPY DOSE AND DOSE INTENSITY ON THE DURATION OF REMISSION IN ACUTE MYELOID-LEUKEMIA

The aim of this study was to assess the influence of dose and dose int ensity (DI) of induction and consolidation chemotherapy on relapse rat es in 264 de novo patients with acute nonlymphocytic leukemia (ANLL). Patients were randomised to receive cytosine arabinoside (ARAC) 100 mg /m(2) continuous infusion for 7 days and daunorubicin (DNR) 50 mg/m(2) IV day 1-3 (7-3) or the same drugs with the addition of etoposide 75 mg/m(2) IV days 1-7 (7-3-7). Cox proportional hazards regression model s were used throughout to identify prognostic factors, including dose delivery parameters, influencing the rate of relapse. Of 152 patients who achieved a complete remission (CR), 104 have relapsed with a media n duration of CR of 15.8 months. Actual dose delivered was prospective ly documented. Cox regression analysis identified the most significant prognostic factors jointly influencing duration of CR as performance status groups (p < 0.0001), percentage peripheral blasts (p = 0.0015), 7-3-7 arm (p = 0.0075), age <40 years (p = 0.022) and induction dose ARA-C plus DNR (p = 0.029). In this analysis patients randomized to th e 7-3-7 arm had an estimated 43% reduction in the relapse rate and eac h 10% reduction of doses ARA-C and DNR was associated with an estimate d 45% increase in the relapse rate. The number of induction courses, d elays in treatment and induction dose intensity did not significantly influence the duration of CR nor did any of the consolidation treatmen t parameters. In conclusion these data suggest that the addition of et oposide and delivery of full induction doses of ARA-C and DNR were the most important treatment parameters influencing the duration of compl ete remission.