Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia : results from Study

Outcomes of patients with acute myeloid leukemia (AML) improve significantly by intensification of induction. To further intensify anthracycline dosage without increasing cardiotoxicity, we compared potentially less cardiotoxic liposomal daunorubicin (L-DNR) to idarubicin at a higher-thanequivalent dose (80 vs 12 mg/m(2) per day for 3 days) during induction. In the multicenter therapyoptimization trial AML-BFM 2004, 521 of 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 [EFS] 59% ± 3% vs 53% ± 3%, Plogrank = .25; cumulative incidence of relapse 29% ± 3% vs 31% ± 3%, P(Gray) = .75), as were EFS results for standard (72% ± 5% vs 68% ± 5%, Plogrank = .47) and high-risk (51% ± 4% vs 46% ± 4%, Plogrank = .45) patients. L-DNR resulted in significantly better probability of EFS in patients with t(8;21). Overall, treatment-related mortality was lower with L-DNR than idarubicin (2/257 vs 10/264 patients, P = .04). Grade 3/4 cardiotoxicity was rare after induction (4 L-DNR vs 5 idarubicin). Only 1 L-DNR and 3 idarubicin patients presented with subclinical or mild cardiomyopathy during follow-up. In conclusion, at the given dose, L-DNR has overall antileukemic activity comparable to idarubicin, promises to be more active in subgroups, and causes less treatment-related mortality. This trial was registered at www.clinicaltrials.gov as NCT00111345. DOI: https://doi.org/10.1182/blood-2013-02-484097 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-84481 Published Version Originally published at: Creutzig, Ursula; Zimmermann, Martin; Bourquin, Jean-Pierre; et al (2013). Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood, 122(1):37-43. DOI: https://doi.org/10.1182/blood-2013-02-484097 doi:10.1182/blood-2013-02-484097 Prepublished online May 23, 2013; 2013 122: 37-43 Dirk Reinhardt von Neuhoff, Jörg Ritter, Annette Sander, André Schrauder, Arend von Stackelberg, Jan Starý and Fleischhack, Norbert Graf, Thomas Klingebiel, Bernhard Kremens, Thomas Lehrnbecher, Christine Ursula Creutzig, Martin Zimmermann, Jean-Pierre Bourquin, Michael N. Dworzak, Gudrun AML-BFM 2004 induction for pediatric acute myeloid leukemia: results from Study Randomized trial comparing liposomal daunorubicin with idarubicin as http://bloodjournal.hematologylibrary.org/content/122/1/37.full.html Updated information and services can be found at: (277 articles) Pediatric Hematology • (1058 articles) Myeloid Neoplasia • (2003 articles) Free Research Articles • (3780 articles) Clinical Trials and Observations • Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: Copyright 2011 by The American Society of Hematology; all rights reserved. Washington DC 20036. by the American Society of Hematology, 2021 L St, NW, Suite 900, Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly For personal use only. at Universitaet Zurich on November 7, 2013. bloodjournal.hematologylibrary.org From