Have we made progress in the treatment of GVHD?

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

One reason for the lack of progress in the treatment of acute graft versus host disease (GVHD) is the lack of reliable biomarkers. GVHD of the gastrointestinal (GI) tract is closely associated with non-relapse mortality (NRM) following hematopoietic cell transplantation (HCT). Using an unbiased, large-scale, quantitative proteomic discovery approach, we identified candidate biomarkers that were increased in plasma from HCT patients with GI GVHD. We then validated the lead candidate, REG3α, by ELISA in samples from more than 1000 HCT patients from three transplant centers. Plasma REG3α concentrations were 3-fold higher in patients at GI GVHD onset than in all other patients. REG3α concentrations correlated most closely with lower GI GVHD at GVHD onset and predicted response to therapy at 4 weeks, 1-year NRM, and 1-year survival (P ≤ 0.001). Multivariate analysis showed that advanced clinical stage, severe histologic damage, and high REG3α concentrations at the diagnosis of GVHD independently predicted 1-year NRM, which progressively increased with higher numbers of onset risk factors present. We conclude that REG3α is a plasma biomarker of GI GVHD that can be combined with clinical stage and histologic grade to improve risk stratification of patients, perhaps providing a platform for advances in the treatment of high-risk GVHD.

Original languageEnglish
Pages (from-to)473-478
Number of pages6
JournalBest Practice and Research in Clinical Haematology
Volume25
Issue number4
DOIs
StatePublished - Dec 2012
Externally publishedYes

Keywords

  • REG3α
  • biomarker
  • gastrointestinal (GI)
  • graft versus host disease (GVHD)
  • hematopoietic cell transplantation (HCT)

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