Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Ursula Creutzig1,*,
  2. Martin Zimmermann1,
  3. Jean-Pierre Bourquin2,
  4. Michael N. Dworzak3,
  5. Gudrun Fleischhack4,
  6. Norbert Graf5,
  7. Thomas Klingebiel6,
  8. Bernhard Kremens4,
  9. Thomas Lehrnbecher6,
  10. Christine von Neuhoff1,
  11. Jörg Ritter7,
  12. Annette Sander1,
  13. André Schrauder8,
  14. Arend von Stackelberg9,
  15. Jan Starý10, and
  16. Dirk Reinhardt1
  1. 1 Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany;
  2. 2 Pediatric Hematology/Oncology, University of Zurich, Zurich, Switzerland;
  3. 3 St. Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria;
  4. 4 Department of Pediatric Hematology, Oncology, University of Essen, Essen, Germany;
  5. 5 Department of Pediatric Oncology and Hematology, Medical School, Saarland University, Homburg, Germany;
  6. 6 Pediatric Hematology, Oncology and Hemostaseology, University Children's Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main, Germany;
  7. 7 Department of Pediatric Hematology and Oncology, University Children's Hospital, Munster, Germany;
  8. 8 Department of Pediatric Hematology/Oncology, University Children's Hospital, Kiel, Germany;
  9. 9 Department of Pediatric Oncology/Hematology, Charite Universitaetsmedizin Berlin, Berlin, Germany;
  10. 10 Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Pediatric Hematology Working Group, Czech Republic
  1. * Corresponding author; email: ursula{at}creutzig.de

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.

Abstract

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. ClinicalTrials.gov Identifier: NCT00111345

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