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Acute myeloid leukemia

Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure

Leukemia volume 31, pages 1306–1313 (2017)Cite this article

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Abstract

We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy. Of the 1025 patients with induction failure, 875 (median age 55 years) received intensive salvage therapy: 7+3-based (n=59), high-dose cytarabine combined with mitoxantrone (HAM; n=150), with all-trans retinoic acid (A; A-HAM) (n=247), with gemtuzumab ozogamicin and A (GO; GO-A-HAM) (n=140), other intensive regimens (n=165), experimental treatment (n=27) and direct allo-HCT (n=87). In patients receiving intensive salvage chemotherapy (n=761), response (complete remission/complete remission with incomplete hematological recovery (CR/CRi)) was associated with GO-A-HAM treatment (odds ratio (OR), 1.93; P=0.002), high-risk cytogenetics (OR, 0.62; P=0.006) and age (OR for a 10-year difference, 0.75; P<0.0001). Better survival probabilities were seen in an extended Cox regression model with time-dependent covariables in patients responding to salvage therapy (P<0.0001) and having the possibility to perform an allo-HCT (P<0.0001). FLT3 internal tandem duplication, mutated IDH1 and adverse cytogenetics were unfavorable factors for survival.

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Acknowledgements

This work was supported by grants from German Bundesministerium für Bildung und Forschung (Grants 01GI9981,01KG0605) and the Deutsche José Carreras Leukämie-Stiftung (Grant DJCLS H 05/02). We are also grateful to all members of the German-Austrian AML Study Group (AMLSG) for providing leukemia specimens and clinical data; a list of AMLSG institutions and investigators participating in this study appears in the Supplementary Appendix.

Author contributions

Conception and design: RF Schlenk and M Wattad; provision of study materials or patients: M Wattad, D Weber, K Döhner, J Krauter, VI Gaidzik, P Paschka, M Heuser, F Thol, T Kindler, M Lübbert, HR Salih, A Kündgen, H-A Horst, P Brossart, K Götze, D Nachbaur, C-H Köhne, M Ringhoffer, G Wulf, G Held, H Salwender, A Benner, A Ganser, H Döhner, and RF Schlenk; collection and assembly of data: RF Schlenk and D Weber; data analysis and interpretation: RF Schlenk, M Wattad, H Döhner and A Benner; manuscript writing: M Wattad, RF Schlenk and H Döhner; final approval of manuscript: M Wattad, D Weber, K Döhner, J Krauter, VI Gaidzik, P Paschka, M Heuser, Fs Thol, T Kindler, M Lübbert, HR Salih, A Kündgen, H-A Horst, P Brossart, K Götze, D Nachbaur, C-H Köhne, M Ringhoffer, G Wulf, G Held, H Salwender, A Benner, A Ganser, H Döhner and RF Schlenk.

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Author notes

  1. J Krauter

    Present address: 19Current address: Klinikum Braunschweig, Braunschweig, Germany.,

Authors and Affiliations

  1. Kliniken Essen Süd, Essen, Germany

    M Wattad

  2. University Hospital of Ulm, Ulm, Germany

    D Weber, K Döhner, V I Gaidzik, P Paschka, H Döhner & R F Schlenk

  3. Hannover Medical School, Hannover, Germany

    J Krauter, M Heuser, F Thol & A Ganser

  4. University Medical Center of Mainz, Mainz, Germany

    T Kindler

  5. University Hospital of Freiburg, Freiburg, Germany

    M Lübbert

  6. University Hospital of Tübingen, Tübingen, Germany

    H R Salih

  7. University Hospital of Düsseldorf, Düsseldorf, Germany

    A Kündgen

  8. University Hospital of Kiel, Kiel, Germany

    H-A Horst

  9. University Hospital of Bonn, Bonn, Germany

    P Brossart

  10. University Hospital of München, Munich, Germany

    K Götze

  11. University Hospital of Innsbruck, Innsbruck, Austria

    D Nachbaur

  12. Klinikum Oldenburg, Oldenburg, Germany

    C-H Köhne

  13. Städtisches Klinikum Karlsruhe, Karlsruhe, Germany

    M Ringhoffer

  14. University Hospital of Göttingen, Göttingen, Germany

    G Wulf

  15. University Hospital of Saarland, Homburg, Germany

    G Held

  16. Asklepios Klinik Altona, Hamburg, Germany

    H Salwender

  17. Division of Biostatistics, German Cancer Research Center Heidelberg, Heidelberg, Germany

    A Benner

  18. NCT Trial Center, National Center for Tumor Diseases (NCT), Heidelberg, Germany

    R F Schlenk

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Presented in part at the 19th Congress of the European Hematology Association, 2014.

Supplementary Information accompanies this paper on the Leukemia website

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Wattad, M., Weber, D., Döhner, K. et al. Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia 31, 1306–1313 (2017). https://doi.org/10.1038/leu.2017.23

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