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Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia

Leukemia volume 18, pages 1798–1803 (2004)Cite this article

Abstract

The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged ⩾61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.

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Acknowledgements

We gratefully acknowledge Brigitte Schreiter and Christa Wieland for technical assistance. This work was supported by Grant 01GI9981 from the Bundesministerium für Bildung und Forschung (Kompetenznetz ‘Akute und chronische Leukämien’), Germany.

Author information

Authors and Affiliations

  1. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    R F Schlenk, S Fröhling, B Addamo, K Döhner & H Döhner

  2. Department of Internal Medicine I, University of Homburg, Germany

    F Hartmann

  3. Städtisches Klinikum, Karlsruhe, Germany

    J Th Fischer

  4. Department of Internal Medicine I, University of Bonn, Germany

    A Glasmacher

  5. Klinikum Oldenburg, Germany

    F del Valle

  6. Klinikum Stuttgart, Germany

    W Grimminger & H G Mergenthaler

  7. Department of Internal Medicine III, Technical University of Munich, Germany

    K Götze

  8. Städtisches Krankenhaus München-Schwabing, Munich, Germany

    C Waterhouse

  9. Department of Internal Medicine, University of Kiel, Germany

    R Schoch

  10. Department of Internal Medicine IV, University of Giessen, Germany

    H Pralle

  11. Department of Internal Medicine V, University of Heidelberg, Germany

    M Hensel

  12. Hanusch-Krankenhaus, Wien, Austria

    E Koller

  13. Krankenhaus der Barmherzigen Brüder, Trier, Germany

    H Kirchen

  14. Caritas-Klinik St Theresia, Saarbrücken, Germany

    J Preiss

  15. Allgemeines Krankenhaus Altona, Hamburg, Germany

    H Salwender

  16. Kreiskrankenhaus, Trostberg, Germany

    H G Biedermann

  17. Caritas Krankenhaus, Lebach, Germany

    S Kremers

  18. Department of Internal Medicine, University of Göttingen, Germany

    F Griesinger

  19. Central Unit of Biostatistics, German Cancer Research Center, Heidelberg, Germany

    A Benner

  20. Department of Hematology, University of Düsseldorf, Germany

    R Haas

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Schlenk, R., Fröhling, S., Hartmann, F. et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia 18, 1798–1803 (2004). https://doi.org/10.1038/sj.leu.2403528

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  • DOI: https://doi.org/10.1038/sj.leu.2403528

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