Advances in the clinical management of GVHD

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29 Scopus citations


The principal cause of mortality and morbidity following hematopoietic cell transplantation (HCT) is graft-versus-host disease (GVHD). Studies in murine models have revealed that inflammatory mediators such as tumor necrosis factor-α (TNF-α) promote destruction of host tissue following HCT. Elevated plasma levels of soluble TNF receptor 1 have been associated with patients with GVHD and blocking TNF-α in experimental models has shown a reduced incidence of GVHD. Based on this finding, patients with new onset GVHD were treated with steroids plus the TNF-α inhibitor, etanercept, on a previously reported pilot trial (n = 20) and a phase 2 trial (n = 41) and their outcomes were compared with those of contemporaneous patients with GVHD (n = 99) whose initial therapy was steroids alone. Patients treated with etanercept were more likely to achieve CR than were patients treated with steroids alone. Plasma TNFR1 levels, a biomarker for GVHD activity, were elevated at GVHD onset and decreased significantly only in patients with CR. A four protein fingerprint of IL-2Rα, TNFR1, IL-8, and HGF in the plasma has been identified to predict whether a patient will be at high-risk for GVHD based on biomarker analysis. In univariate and multivariate analysis, this four-protein fingerprint has shown a strong association with the grade of acute GVHD, and it can stratify patients into low- and high-risk groups and can be used as a laboratory-based screening method, to diagnose and perhaps treat patients preemptively.

Original languageEnglish
Pages (from-to)677-682
Number of pages6
JournalBest Practice and Research: Clinical Haematology
Issue number4
StatePublished - Dec 2008
Externally publishedYes


  • TNF receptor I
  • antigen-presenting cells
  • cytotoxic T cells
  • etanercept
  • graft-versus-host-disease (GVHD)
  • graft-versus-leukemia (GVL)
  • lipopolysaccharide
  • natural killer cells
  • steroids
  • tumor necrosis factor-α (TNF-α)


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