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  • Original Article
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Acute myeloid leukemia

Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia

Leukemia volume 30, pages 1230–1236 (2016)Cite this article

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Abstract

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ⩾60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ⩾5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.

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Acknowledgements

This study was funded by the Deutsche Krebshilfe (70-2839-Bü4). RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Professors Elihu Estey (University Washington) and Charles Schiffer (Wayne State University) kindly reviewed the typescript and provided helpful comments. The participating institutions are listed in the supplement.

Author information

Author notes

  1. U Krug

    Present address: 21Current address: Klinikum Leverkusen, Department of Medicine 3, Leverkusen, Germany.,

  2. C Müller-Tidow

    Present address: 22Current address: University Hospital, Department of Medicine IV, Halle, Germany.,

  3. J Braess

    Present address: 23Current address: Krankenhaus der Barmherzigen Brüder, Department of Oncology and Hematology, Regensburg, Germany.,

  4. P Staib

    Present address: 24Current address: St. Antonius Krankenhaus, Department of Hematology, Oncology and Palliative Care, Eschweiler, Germany.,

  5. A Giagounidis

    Present address: 25Current address: Marienkrankenhaus, Department of Oncology, Hematology and Palliative Care, Düsseldorf, Germany.,

  6. B J Wörmann

    Present address: 26Current address: German Society of Hematology and Oncology, Berlin, Germany.,

Authors and Affiliations

  1. Department of Medicine A, University Hospital, Muenster, Germany

    U Krug, W E Berdel, C Müller-Tidow, C Schliemann, M Stelljes & T Büchner

  2. Celgene Inc., Summit, NJ, USA

    R P Gale

  3. Munich Leukemia Laboratory, Munich, Germany

    C Haferlach, W Kern & T Haferlach

  4. Munich, Germany

    S Schnittger

  5. IIIrd Department of Medicine, University Hospital Großhadern, Munich, Germany

    J Braess, K Spiekermann & W Hiddemann

  6. Department of Medicine 1, University Hospital, Cologne, Germany

    P Staib

  7. Department of Bone Marrow Transplantation, University Hospital, Essen, Germany

    D Beelen

  8. Department of Medicine II, University Hospital, Frankfurt, Germany

    H Serve

  9. Department of Hematology, Evangelisches Krankenhaus, Oncology and Palliative Care, Hamm, Germany

    L Balleisen

  10. Department of Hematology, Klinikum Ernst von Bergmann, Oncology and Palliative Care, Berlin, Germany

    G Maschmeyer

  11. Department of Hematology, Vivantes Hospital Neukölln, Oncology and Palliative Care, Berlin, Germany

    A Grüneisen

  12. Department of Medicine and Oncology, Allgemeines Krankenhaus, Hagen, Germany

    H Eimermacher

  13. Department of Oncology and Hematology, Helios Klinikum, Duisburg, Germany

    A Giagounidis & C Aul

  14. Department of Medicine I, Klinikum Bremen Mitte, Bremen, Germany

    H Rasche

  15. Department of Hematology and Oncology, University Hospital, Mannheim, Germany

    R Hehlmann & E Lengfelder

  16. Department of Hematology, Oncology and Tumor Immunology, University Hospital Charité – Benjamin Franklin, Berlin, Germany

    E Thiel

  17. Department of Medicine III, University Hospital, Regensburg, Germany

    A Reichle

  18. Department of Hematology, Helios Klinikum Berlin-Buch, Oncology, Tumor Immunology and Palliative Medicine, Berlin, Germany

    W-D Ludwig

  19. University of Münster, Institute of Biostatistics and Clinical Research, Münster, Germany

    W Köpcke, D Görlich, M C Sauerland & A Heinecke

  20. Department of Medicine III, Klinikum Braunschweig, Braunschweig, Germany

    B J Wörmann

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  1. U Krug
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  33. W Hiddemann
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for the German Acute Myeloid Leukemia Cooperative Group (AMLCG)

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Correspondence to U Krug.

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Krug, U., Berdel, W., Gale, R. et al. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia. Leukemia 30, 1230–1236 (2016). https://doi.org/10.1038/leu.2016.25

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