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Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation

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Abstract

We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In multivariate analysis, mutated NRAS, U2AF1, IDH2, and TP53 and/or a complex karyotype were significant prognostic markers for OS besides age above 60 years, remission status, IPSS-R cytogenetic risk, HCT-CI > 2 and female donor sex. Mutated NRAS, IDH1, EZH2, and TP53 and/or a complex karyotype were genetic aberrations with prognostic impact on CIR. No molecular markers were associated with the risk of NRM. The inclusion of molecular information results in better risk prediction models for OS and CIR when assessed by the Akaike information criterion. Internal cross validation confirmed the robustness of our comprehensive risk model. In summary, we propose to combine molecular, cytogenetic, and patient- and transplantation-associated risk factors into a comprehensive risk model to provide personalized predictions of outcome after alloHCT.

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Acknowledgements

We are indebted to all patients and contributing doctors. We thank Elke Dammann for the documentation of clinical data.

This study was supported by the German Federal Ministry of Education and Research grant 01EO0802 (IFB-Tx); grants 110284, 110287, 110292, and 70111267 from Deutsche Krebshilfe; grant DJCLS R13/14 from the Deutsche José Carreras Leukämie-Stiftung e.V; DFG grant HE 5240/5-2 and HE 5240/6-1; an ERC grant under the European Union’s Horizon 2020 research and innovation programme (No. 638035); and grants from Dieter-Schlag Stiftung.

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  1. Michael Heuser and Razif Gabdoulline have equal contribution as first authors.

Authors and Affiliations

  1. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany

    Michael Heuser, Razif Gabdoulline, Patrick Löffeld, Vera Dobbernack, Henriette Kreimeyer, Mira Pankratz, Madita Flintrop, Alessandro Liebich, Sabrina Klesse, Victoria Panagiota, Michael Stadler, Martin Wichmann, Rabia Shahswar, Arnold Ganser, Christian Koenecke & Felicitas Thol

  2. Medizinische Klinik und Poliklinik I, Universtitätsklinikum Carl Gustav Carus, Dresden, Germany

    Uwe Platzbecker & Christian Thiede

  3. Klinik für Hämatologie, Onkologie und Klinische Immunologie, Heinrich Heine University, Düsseldorf, Germany

    Thomas Schroeder, Guido Kobbe & Ulrich Germing

  4. Helmholtz Centre for Infection Research, Braunschweig, Germany

    Robert Geffers

  5. Institute of Human Genetics, Hannover Medical School, Hannover, Germany

    Brigitte Schlegelberger & Gudrun Göhring

  6. Institute of Pathology, Hannover Medical School, Hannover, Germany

    Hans-Heinrich Kreipe

  7. Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Nicolaus Kröger

Authors
  1. Michael Heuser
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  2. Razif Gabdoulline
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  26. Felicitas Thol
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Correspondence to Michael Heuser.

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The authors declare that they have no conflict of interest.

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Christian Koenecke and Felicitas Thol share senior authorship.

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Heuser, M., Gabdoulline, R., Löffeld, P. et al. Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation. Ann Hematol 96, 1361–1372 (2017). https://doi.org/10.1007/s00277-017-3027-5

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  • DOI: https://doi.org/10.1007/s00277-017-3027-5

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