Randomized trial comparing liposomal daunorubicin with idarubicin in induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004

Ursula Creutzig, Martin Zimmermann, Jean-Pierre Bourquin, Michael N. Dworzak, Gudrun Fleischhack, Norbert Graf, Thomas Klingebiel, Bernhard Kremens, Thomas Lehrnbecher, Christine von Neuhoff, Jörg Ritter, Annette Sander, André Schrauder, Arend von Stackelberg, Jan Starý and Dirk Reinhardt

Key points

  • AML induction with liposomal daunorubicin (80mg/sqm/d/x3) shows an overall anti-leukemic activity comparable to idarubicin (12mg/m/d/x3).

  • Liposomal daunorubicin promises to be more active in the subgroup t(8;21) and causes less treatment related toxicity.


Outcome of adult and pediatric patients with AML improved significantly by intensification of induction treatment. To further intensify anthracycline-dosage without increasing cardiotoxicity, we compared the potentially less cardiotoxic liposomal daunorubicin (L-DNR) at a higher than equivalent dose (80mg/m2/day/x3) to idarubicin (12mg/m2/day/x3) during induction. In study AML-BFM 2004, 521/611 pediatric patients (85%) were randomly assigned to L-DNR or idarubicin induction. Five-year results in both treatment arms were similar (overall survival: 76%±3% [L-DNR] vs. 75%±3% [idarubicin], plogrank=.65, event-free survival [pEFS]: 59%±3% vs. 53%±3%, plogrank=.25; cumulative incidence of relapse: 29%±3% vs. 31%±3%, p(Gray)=0.75), as were EFS results for standard (72%±5% vs. 68%±5%, plogrank=.47) and high-risk patients (51%±4% vs. 46%±4%, plogrank=.45). L-DNR resulted in significantly better pEFS in t(8;21) patients. Overall, treatment-related mortality (TRM), was lower in the L-DNR- than in the idarubicin-group (2/257 vs. 10/264 patients, p=.04). Grade III/IV cardiotoxicity was rare after induction (4 L-DNR- vs. 5 idarubicin-patients). Only one L-DNR- and 3 idarubicin-patients presented with subclinical or mild cardiomyopathy during follow-up. We conclude that L-DNR has - at the given dose - an overall anti-leukemic activity comparable to idarubicin, promises to be more active in subgroups, and causes less TRM. These results with high survival rates support its use in the forthcoming AML-BFM trial. Identifier: NCT00111345

  • Submitted February 12, 2013.
  • Accepted April 17, 2013.