Biology of Blood and Marrow Transplantation
Volume 12, Issue 2 , Pages 126-137, February 2006

Toward Biomarkers for Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. Biomarker Working Group Report

  • Kirk R. Schultz

      Affiliations

    • British Columbia Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    • Corresponding Author InformationCorrespondence and reprint requests: Kirk R. Schultz, MD, Pediatric Hematology/Oncology/Bone Marrow Transplant, University of British Columbia, British Columbia’s Children’s Hospital, 4480 Oak St, Room A119, Vancouver, British Columbia V6H 3V4, Canada
    • ,
  • David B. Miklos

      Affiliations

    • Stanford University Medical Center, Stanford, California
    • ,
  • Daniel Fowler

      Affiliations

    • National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland
    • ,
  • Ken Cooke

      Affiliations

    • University of Michigan Medical Center, Ann Arbor, Michigan
    • ,
  • Judith Shizuru

      Affiliations

    • Stanford University Medical Center, Stanford, California
    • ,
  • Emmanuel Zorn

      Affiliations

    • Brigham and Women’s Hospital, Harvard University, Boston, Massachusetts
    • ,
  • Ernst Holler

      Affiliations

    • University of Regensburg, Regensburg, Germany
    • ,
  • James Ferrara

      Affiliations

    • University of Michigan Medical Center, Ann Arbor, Michigan
    • ,
  • Howard Shulman

      Affiliations

    • Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington
    • ,
  • Stephanie J. Lee

      Affiliations

    • Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • Paul Martin

      Affiliations

    • Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington
    • ,
  • Alexandra H. Filipovich

      Affiliations

    • Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio
    • ,
  • Mary E.D. Flowers

      Affiliations

    • Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington
    • ,
  • Daniel Weisdorf

      Affiliations

    • University of Minnesota, Minneapolis, Minnesota
    • ,
  • Daniel Couriel

      Affiliations

    • M.D. Anderson Cancer Center, University of Texas, Houston, Texas
    • ,
  • Peter A. Lachenbruch

      Affiliations

    • US Food and Drug Administration, Rockville, Maryland
    • ,
  • Barbara Mittleman

      Affiliations

    • National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
    • ,
  • Georgia B. Vogelsang

      Affiliations

    • Johns Hopkins University School of Medicine, Baltimore, Maryland
    • ,
  • Steven Z. Pavletic

      Affiliations

    • National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland

Received 10 November 2005; accepted 11 November 2005.

Abstract 

Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials.

Key Words:  Graft-versus-host disease , Biomarkers

 

 This project was supported by the National Institutes of Health (NIH) National Cancer Institute, Office of the Director, Cancer Therapy Evaluation Program, Intramural Research Program and Center for Cancer Research; National Heart Lung and Blood Institute, Division of Blood Diseases and Resources; Office of Rare Diseases, NIH, Office of the Director; National Institute of Allergy and Infectious Disease, Transplantation Immunology Branch; and the Health Resources and Services Administration, Division of Transplantation and the Naval Medical Research Center, C. W. Bill Young/Department of Defense Marrow Donor Recruitment and Research Program.The opinions expressed here are those of the authors and do not represent the official position of the National Institutes of Health or the US Government.

PII: S1083-8791(05)00783-4

doi:10.1016/j.bbmt.2005.11.010

Biology of Blood and Marrow Transplantation
Volume 12, Issue 2 , Pages 126-137, February 2006

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