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Transplant Toxicities

Predicting survival using clinical risk scores and non-HLA immunogenetics

Bone Marrow Transplantation volume 50, pages 1445–1452 (2015)Cite this article

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Abstract

Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.

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Acknowledgements

This work was supported by the Marie Curie Research Training Network (MCRTN) grant CT-2004-512253: TRANSNET (European Commission), grant LSHB-CT-2007-037703: Stemdiagnostics (European Commission), the German Research Foundation (DFG), grant GRK 1034, the Marie Curie Initial Training Network (MCITN) grant 315963: CELLEUROPE, and the Deutsche José Carreras Leukämie-Stiftung. We thank Andrew Entwistle for his support in reviewing and proofreading the manuscript.

Author information

Author notes

  1. Y Balavarca

    Present address: Department of Preventive Oncology, National Center for Tumour Diseases and German Cancer Research Center, Heidelberg, Germany.,

  2. A Dickinson and H Bickeböller: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetic Epidemiology, University Medical Center, Göttingen, Germany

    Y Balavarca & H Bickeböller

  2. Department of Haematological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK

    K Pearce, J Norden, M Collin & A Dickinson

  3. Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

    G Jackson

  4. Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany

    E Holler & D Wolff

  5. Department of Cellular and Molecular Immunology, University Medical Center, Göttingen, Germany

    R Dressel

  6. Department of Haematology and Oncology, Klinikum Grosshadern, Medical Klinik III, Munich, Germany

    H-J Kolb

  7. Department of Haematology, Division of Haematology, Medical University of Graz, Graz, Austria

    H Greinix

  8. Department of Haematology, Immunology and Oncology, AP-HP, Saint Louis Hospital, Hematology Transplantation, Paris, France

    G Socie

  9. Departement d′Immunologie, Université Paris Diderot, INSERM UMRS-940, AP-HP, Paris, France

    A Toubert

  10. Department of Bone Marrow Transplantation, EUROCORD, St Louis Hospital, Paris, France

    V Rocha & E Gluckman

  11. Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

    I Hromadnikova

  12. Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    P Sedlacek

  13. Department I of Internal Medicine, University of Cologne, Cologne, Germany

    U Holtick

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  1. Y Balavarca
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Correspondence to K Pearce.

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Balavarca, Y., Pearce, K., Norden, J. et al. Predicting survival using clinical risk scores and non-HLA immunogenetics. Bone Marrow Transplant 50, 1445–1452 (2015). https://doi.org/10.1038/bmt.2015.173

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