Biology of Blood and Marrow Transplantation
Volume 16, Issue 5 , Pages 565-586, May 2010

NCI First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biology Underlying Recurrence of Malignant Disease following Allogeneic HSCT: Graft-versus-Tumor/Leukemia Reaction

  • Jeffrey S. Miller

      Affiliations

    • Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota
    • Corresponding Author InformationCorrespondence and reprint requests: Jeffrey S. Miller, MD, University of Minnesota, 420 Delaware Street, SE, MMC 806, Minneapolis, MN 55455.
    • ,
  • Edus H. Warren

      Affiliations

    • Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • ,
  • Marcel R.M. van den Brink

      Affiliations

    • Departments of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York
    • ,
  • Jerome Ritz

      Affiliations

    • Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • Warren D. Shlomchik

      Affiliations

    • Section of Medical Oncology, Cancer Center, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • William J. Murphy

      Affiliations

    • University of California, Davis Medical Center, Sacramento, California
    • ,
  • A. John Barrett

      Affiliations

    • Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Hans Jochem Kolb

      Affiliations

    • Hematopoietic Cell Transplantation, Department of Medicine III, University of Munich, Munich, Germany
    • ,
  • Sergio Giralt

      Affiliations

    • Department of Stem Cell Transplantation, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
    • ,
  • Michael R. Bishop

      Affiliations

    • Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Bruce R. Blazar

      Affiliations

    • Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • J.H. Frederik Falkenburg

      Affiliations

    • Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

Received 3 February 2010; accepted 5 February 2010. published online 11 February 2010.

The success of allogeneic hematopoietic stem cell transplantation (HSCT) depends on the infusion of benign stem cells as well as lymphocytes capable of participating in a graft-versus-tumor/leukemia (GVL) reaction. Clinical proof of concept is derived from studies showing increased relapse after the infusion of lymphocyte depleted hematopoietic grafts as well as the therapeutic efficacy of donor lymphocyte infusions without chemotherapy to treat relapse in some diseases. Despite this knowledge, relapse after allogeneic HSCT is common with rates approaching 40% in those with high-risk disease. In this review, we cover the basic biology and potential application to exploit adaptive T cell responses, minor histocompatibility antigens, contraction and suppression mechanisms that hinder immune responses, adaptive B cell responses and innate NK cell responses, all orchestrated in a GVL reaction. Optimal strategies to precisely balance immune responses to favor GVL without harmful graft-versus-host disease (GVHD) are needed to protect against relapse, treat persistent disease and improve disease-free survival after HSCT.

Key Words: HCT, relapse, Graft-versus-host disease, Immune modulation, Graft-versus-leukemia reaction

 

 Financial disclosure: See Acknowledgments on page 581.

PII: S1083-8791(10)00060-1

doi:10.1016/j.bbmt.2010.02.005

Biology of Blood and Marrow Transplantation
Volume 16, Issue 5 , Pages 565-586, May 2010

Article Tools

* Image Usage & Resolution