Blood Journal
Leading the way in experimental and clinical research in hematology

Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study

  1. John E. Levine1,
  2. Brent R. Logan2,
  3. Juan Wu3,
  4. Amin M. Alousi4,
  5. Javier Bolaños-Meade5,
  6. James L. M. Ferrara1,
  7. Vincent T. Ho6,
  8. Daniel J. Weisdorf7, and
  9. Sophie Paczesny1
  1. 1University of Michigan Blood and Marrow Transplant Program, Ann Arbor, MI;
  2. 2Medical College of Wisconsin Division of Biostatistics, Milwaukee, MN;
  3. 3The EMMES Corporation, Rockville, MD;
  4. 4The University of Texas MD Anderson Cancer Center, Department of Stem Cell Transplantation, Houston, TX;
  5. 5Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, Baltimore, MD;
  6. 6Dana-Farber/Harvard Cancer Institute, Boston, MA; and
  7. 7University of Minnesota Medical Center Blood and Marrow Transplant Program, Minneapolis, MN

Abstract

Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation, and once it develops, there are no reliable diagnostic tests to predict treatment outcomes. We hypothesized that 6 previously validated diagnostic biomarkers of GVHD (IL-2 receptor-α; tumor necrosis factor receptor-1; hepatocyte growth factor; IL-8; elafin, a skin-specific marker; and regenerating islet–derived 3-α, a gastrointestinal tract–specific marker) could discriminate between therapy responsive and nonresponsive patients and predict survival in patients receiving GVHD therapy. We measured GVHD biomarker concentrations from samples prospectively obtained at the initiation of treatment, day 14, and day 28, on a multicenter, randomized, 4-arm phase 2 clinical trial for newly diagnosed acute GVHD. We found that at each of 3 time points, GVHD onset, 2 weeks into treatment, and 4 weeks into treatment, a 6-protein biomarker panel predicted for the important clinical outcomes of day 28 posttherapy nonresponse and mortality at day 180 from onset. GVHD biomarker panels can be used for early identification of patients at high or low risk for treatment nonresponsiveness or death, and they may provide opportunities for early intervention and improved survival after hematopoietic cell transplantation. The study was registered in clinicaltrials.gov as NCT00224874.

  • Submitted January 9, 2012.
  • Accepted February 25, 2012.
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