Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n 5 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m² twice a day for 2 days plus idarubicin; n 5 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P 5 .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P 5 .0007) with lower resistance risk (P, .0001), comparable mortality (P 5 .39), and improved 5-year overall survival (39% vs 49%; P 5 .045) and relapse-free survival (36% vs 48%; P 5 .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P 5 .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P 5 .003), and also improved overall/ relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P 5 .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P 5 .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.