Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease

Haematologica. 2012 Nov;97(11):1674-7. doi: 10.3324/haematol.2011.061051. Epub 2012 Jun 11.

Abstract

Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and nonrelapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease-Free Survival
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Female
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / metabolism
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / pathology
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Intestinal Diseases* / drug therapy
  • Intestinal Diseases* / metabolism
  • Intestinal Diseases* / mortality
  • Intestinal Diseases* / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Steroids / administration & dosage*
  • Survival Rate
  • Thrombomodulin / biosynthesis*
  • Transplantation, Homologous

Substances

  • Steroids
  • THBD protein, human
  • Thrombomodulin