title: Have we made progress in the treatment of GVHD?
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.
authors.affiliation: University of Michigan Medical School, 6303 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 4810, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Harris
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
mesh_terms: D000208:Acute Disease; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007410:Intestinal Diseases / Q000097:blood / Q000401:mortality / Q000628:therapy; D037181:Lectins, C-Type / Q000097:blood*; D000073718:Pancreatitis-Associated Proteins; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human