title: Plasma biomarkers of lower gastrointestinal and liver acute GVHD.
abstract: The lower gastrointestinal tract (LGI) and liver are the GVHD target organs most associated with treatment failure and nonrelapse mortality. We recently identified regenerating islet-derived 3-α (REG3α) as a plasma biomarker of LGI GVHD. We compared REG3α with 2 previously reported GI and liver GVHD diagnostic biomarkers, hepatocyte growth factor (HGF) and cytokeratin fragment 18, in 954 hematopoietic cell transplantation patients. All 3 biomarkers were significantly elevated in LGI GVHD compared with non-GVHD diarrhea; REG3α discerned LGI GVHD from non-GVHD diarrhea better than HGF and cytokeratin fragment 18. Although all 3 biomarkers predicted nonresponse to therapy at day 28 in LGI GVHD patients, only REG3α and HGF concentrations predicted 1-year nonrelapse mortality (P = .01 and P = .02, respectively). Liver GVHD without GI involvement at GVHD onset and non-GVHD liver complications were uncommon; all 3 biomarkers were elevated in liver GVHD, but did not distinguish GVHD from other causes of hyperbilirubinemia.
authors.affiliation: Blood and Marrow Transplant Program, The University of Michigan, Ann Arbor, MI 48109-5942, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Harris
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Sung W
authors.initials: SW
authors.lastname: Choi
authors.forename: Karin
authors.initials: K
authors.lastname: Landfried
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Mark
authors.initials: M
authors.lastname: Vander Lugt
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Couriel
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology; D006086:Graft vs Host Disease / Q000097:blood* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053538:Keratin-18 / Q000097:blood; D037181:Lectins, C-Type / Q000097:blood*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D012372:ROC Curve; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D053538:Keratin-18; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D017228:Hepatocyte Growth Factor