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Biomarkers in chronic graft-versus-host disease: quo vadis?

Bone Marrow Transplantation volume 53, pages 832–837 (2018)Cite this article

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Abstract

Biomarkers are increasingly used for diagnosis and treatment of transplant-related complications including the first biomarker-driven interventional trials of acute graft-versus-host disease (GvHD). In contrast, the development of biomarkers of chronic GvHD (cGvHD) has lagged behind due to a broader variety of manifestations, overlap with acute GvHD, a greater variation in time to onset and maximum severity, and lack of sufficient patient numbers within prospective trials. An international workshop organized by a North-American and European consortium was held in Marseille in March 2017 with the goal to discuss strategies for future biomarker development to guide cGvHD therapy. As a result of this meeting, two areas were prioritized: the development of prognostic biomarkers for subsequent onset of moderate/severe cGvHD, and in parallel, the development of qualified clinical-grade assays for biomarker quantification. The most promising prognostic serum biomarkers are CXCL9, ST2, matrix metalloproteinase-3, osteopontin, CXCL10, CXCL11, and CD163. Urine-proteomics and cellular subsets (CD4+ T-cell subsets, NK cell subsets, and CD19+CD21low B cells) represent additional potential prognostic biomarkers of cGvHD. A joint effort is required to verify the results of numerous exploratory trials before any of the potential candidates is ready for validation and subsequent clinical application.

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Acknowledgements

DW received support from the German José Carreras Foundation. The conference was supported by the Meredith A. Cowden foundation, Mallinckrodt, Incyte Inc., Gilead Sciences, Inc., Jazz Pharmaceuticals, Miltenyi, Metabolon, and Beckman Coulter.

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Authors and Affiliations

  1. Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany

    D. Wolff, E. Holler & M. Edinger

  2. Division of Haematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    H. Greinix

  3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    S. J. Lee, T. Gooley & J. A. Hansen

  4. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    S. Paczesny

  5. Experimental Transplantation and Immunology Branch, Center of Cancer Research, National Cancer Institute, Bethesda, MD, USA

    S. Pavletic & F. Hakim

  6. Hematology Department, Hôpital Saint-Antoine; Université Pierre & Marie Curie; and INSERM, Centre de Recherche Saint-Antoine, UMRS U938, Paris, France

    F. Malard

  7. Department of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    M. Jagasia

  8. St. Anna Children’s Hospital, Medical University Vienna, Vienna, Austria

    A. Lawitschka

  9. Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, and Medical School University of Zagreb, Zagreb, Croatia

    D. Pulanic

  10. Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia

    D. Pulanic

  11. Institute of Cellular Medicine, Newcastle University, Newcastle, UK

    A. Dickinson

  12. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    E. Weissinger

  13. Department of Medicine, Division of Hematological Malignancies & Cellular Therapy, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

    S. Sarantopoulos

  14. Michael Cuccione Childhood Cancer Research Program, British Columbia Children’s Hospital/University of British Columbia, Vancouver, BC, Canada

    K. R. Schultz

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Correspondence to D. Wolff.

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Conflict of interest

SP is an inventor on a patent on “Methods of detection of graft-versus-host disease” licensed to Viracor-IBT Laboratories. The remaining authors declare that they have no conflict of interest.

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Wolff, D., Greinix, H., Lee, S.J. et al. Biomarkers in chronic graft-versus-host disease: quo vadis?. Bone Marrow Transplant 53, 832–837 (2018). https://doi.org/10.1038/s41409-018-0092-x

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