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Acute myeloid leukemia

Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Leukemia volume 31, pages 26–33 (2017)Cite this article

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Abstract

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.

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Acknowledgements

We thank the Leukemia Working Group of the HOVON/SAKK Cooperative Groups and the Leukemia Working Group of the EORTC for conception and design; Martine Testroote, Ine Meulendijks, Christel van Hooije (HOVON) and Christine Biaggi (SAKK) for collection and assembly of data. Stefan Suciu (EORTC) and Myriam Labopin (EBMT) are acknowledged for completing clinical data. Joop H. Jansen (EORTC) is highly acknowledged for molecular analysis of patients.

Author contributions

JV, FEMitH, GH and JJC contributed to the study design; all authors provided study materials or patients; all authors were involved in collection and assembly of clinical data; JV, FEMitH, GH and JJC were involved in analysing and interpreting the data and writing this report; and all authors reviewed and approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands

    J Versluis, R Devillier, P J M Valk, B Löwenberg & J J Cornelissen

  2. Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    F E M in ‘t Hout & G Huls

  3. Department of Laboratory medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    F E M in ‘t Hout & B A van der Reijden

  4. HOVON Data Center, Erasmus University Medical Center Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands

    W L J van Putten

  5. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    M G Manz

  6. Department of Hematology, Hôpital St Luc, Brussels, Belgium

    M -C Vekemans

  7. Department of Hematology, Medisch Spectrum Twente, Enschede, The Netherlands

    M -C Legdeur

  8. Stem Cell Transplant Team, University Hospital Basel, Basel, Switzerland

    J R Passweg

  9. Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

    J Maertens

  10. Department of Immunology and Hematology, University Medical Center, Utrecht, The Netherlands

    J Kuball

  11. Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    B J Biemond

  12. Department of Cellular Biotechnologies and Hematology, ‘Sapienza’ University, Rome, Italy

    G Meloni

  13. Department of Hematology, University Hospital Maastricht, Maastricht, The Netherlands

    H C Schouten

  14. Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands

    E Vellenga

  15. Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland

    T Pabst

  16. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    R Willemze

  17. Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

    G Ossenkoppele

  18. Department of Hematology, University of Liège, Liège, Belgium

    F Baron

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  1. J Versluis
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Correspondence to J J Cornelissen.

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Presented by the first author as an oral presentation at the 56th Annual Meeting of the American Society of Hematology, 6–9 December 2014, San Francisco, CA, USA; and at the 9th Dutch Hematology Congress, 21–23 January 2015, Arnhem, The Netherlands.

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Versluis, J., in ‘t Hout, F., Devillier, R. et al. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio. Leukemia 31, 26–33 (2017). https://doi.org/10.1038/leu.2016.183

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