November 25, 2011
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Biomarker may detect GVHD of the gastrointestinal tract after HSCT

Ferrara JL. Blood. 2011;doi:10.1182/blood-2011-08-375006.

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Researchers have discovered a plasma biomarker that they said will enable physicians to identify patients with cancer who are at the greatest risk for graft-versus-host disease after being treated with hematopoietic stem cell transplantation.

Multivariate analysis showed that advanced clinical stage, severe histologic damage and high concentrations of the regenerating islet-derived protein 3-alpha (REG3A) at graft-versus-host disease (GVHD) diagnosis were independent predictors for 1-year non-relapse mortality.

Using an unbiased, large-scale, quantitative proteomic discovery approach, researchers identified a twofold increase in the presence of 74 proteins in plasma collected from 1,014 patients with gastrointestinal GVHD treated with hematopoietic stem cell transplantation (HSCT). Five of those proteins were gastrointestinal in origin, and researchers found that concentrations of REG3A were three times higher in patients at GVHD- onset compared with other patients.

Researchers at centers in Regensburg, Germany, and Kyushu, Japan, collected heparinized blood samples for 4 weeks after allogeneic HSCT, then monthly for 2 months, and at the time of key clinical events, such as the development of symptoms associated with GVHD.

The discovery set consisted of plasma samples from 10 patients treated with HSCT at the onset of biopsy-proven GVHD, and 10 patients treated with HSCT who never developed GVHD and who were matched for key transplant characteristics.

The researchers said the plasma concentrations of REG3A in the individual plasma samples in the discovery set were four times higher in the patients with GVHD compared with asymptomatic controls. When researchers then evaluated REG3A plasma concentration as a biomarker of GVHD in samples from a validation set of 871 allogeneic HSCT recipients from the University of Michigan, they found plasma REG3A concentrations were three times higher in patients at the onset of GVHD.

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