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Minimal Residual Disease

Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse

Leukemia volume 29, pages 377–386 (2015)Cite this article

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Abstract

In acute myeloid leukemia (AML), assessment of minimal residual disease (MRD) by flow cytometry (flow MRD) after induction and consolidation therapy has been shown to provide independent prognostic information. However, data on the value of earlier flow MRD assessment are lacking. Therefore, the value of flow MRD detection was determined during aplasia in 178 patients achieving complete remission after treatment according to AMLCG (AML Cooperative Group) induction protocols. Flow MRD positivity during aplasia predicted poor outcome (5-year relapse-free survival (RFS) 16% vs 43%, P<0.001) independently from age and cytogenetic risk group (hazard ratio for MRD positivity 1.71; P=0.009). Importantly, the prognosis of patients without detectable MRD was neither impacted by morphological blast count during aplasia nor by MRD status postinduction. Early flow MRD was also evaluated in the context of existing risk factors. Flow MRD was prognostic within the intermediate cytogenetic risk group (5-year RFS 15% vs 37%, P=0.016) as well as for patients with normal karyotype and NPM1 mutations (5-year RFS 13% vs 49%, P=0.02) or FLT3-ITD (3-year RFS rates 9% vs 44%, P=0.016). Early flow MRD assessment can improve current risk stratification approaches by prediction of RFS in AML and might facilitate adaptation of postremission therapy for patients at high risk of relapse.

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Acknowledgements

We thank the participating centers of the AMLCG clinical trial. Furthermore, we also thank Elke Habben, Karin Hecht and Ewelina Zientara (Laboratory for Leukemia Diagnostics, University Hospital Munich, Munich, Germany) for their excellent technical support. This work was supported by the Deutsche Krebshilfe grant 109031. WH, KS and SKB received support from the Deutsche Forschungsgemeinschaft (SFB684, projects A6, A12).

Author contributions

TK, DS, KR and MH collected and analyzed the data; SKB, PMK and SS were responsible for genetic analyses; AD and KS performed assessment of NPM1; WEB, TB, BH, JB and WH coordinated the AMLCG clinical trial; RPL and EH provided advice for statistical analyses; TK and DS wrote the manuscript; KS aided in the supervision of the project; MS is head of the flow cytometry unit at the Laboratory of Leukemia Diagnostics and designed the research, interpreted the data and supervised the project.

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Authors and Affiliations

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

    T Köhnke, D Sauter, K Ringel, E Hoster, M Hubmann, S K Bohlander, S Schneider, A Dufour, W Hiddemann, K Spiekermann & M Subklewe

  2. Institute of Medical Informatics, Biometry and Epidemiology (IBE), University of Munich, Munich, Germany

    E Hoster & R P Laubender

  3. Department of Human Genetics, Philipps University Marburg, Marburg, Germany

    S K Bohlander & P M Kakadia

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

    M-C Sauerland

  5. Department of Internal Medicine IIIA, University of Münster, Münster, Germany

    W E Berdel & T Büchner

  6. German Society of Hematology and Oncology (DGHO), Berlin, Germany

    B Wörmann

  7. Department of Hematology and Oncology, Barmherzige Brüder Hospital, Regensburg, Germany

    J Braess

  8. Clinical Cooperation Group Acute Myeloid Leukemia, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany

    W Hiddemann & K Spiekermann

  9. German Cancer Consortium (DKTK), Heidelberg, Germany

    K Spiekermann

  10. German Cancer Research Centre (DKFZ), Heidelberg, Germany

    K Spiekermann

  11. Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany

    M Subklewe

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  1. T Köhnke
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Correspondence to M Subklewe.

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Köhnke, T., Sauter, D., Ringel, K. et al. Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse. Leukemia 29, 377–386 (2015). https://doi.org/10.1038/leu.2014.186

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  • DOI: https://doi.org/10.1038/leu.2014.186

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