title: Prediction of veno-occlusive disease using biomarkers of endothelial injury.
abstract: Predicting the development of veno-occlusive disease (VOD) of the liver remains challenging. We hypothesized that biomarkers of endothelial injury in myeloablative allogeneic transplantation recipients could predict VOD occurrence. We evaluated 4 biomarkers-von Willebrand Factor (vWF), thrombomodulin, E-selectin, and soluble intercellular adhesion molecule-1 (sICAM-1)-weekly in the peritransplantation period in an attempt to predict VOD. In the patients who received sirolimus, vWF, thrombomodulin, and sICAM-1 levels were significantly elevated in patients with VOD compared with those without VOD on day -1 (P <or= .035), day +7 (P <or= .0001), and day +14 (P <or= .004). E-selectin was predictive on day +7 (P = .007). Levels of vWF >or=1400 IU/mL and thrombomodulin >or=100 ng/mL on day +7 were both 100% sensitive and 100% specific in predicting VOD. These biomarkers were informative when adjusted for other risk factors for VOD in regression analysis. Among patients not receiving sirolimus, biomarkers of endothelial injury were not informative. We conclude that vWF, thrombomodulin, and sICAM-1 elevations before and early after transplantation may be useful in predicting VOD in patients receiving sirolimus.
authors.affiliation: Division of Hematologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. corey_cutler@dfci.harvard.edu
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Shaké
authors.initials: S
authors.lastname: Ayanian
authors.forename: Gary
authors.initials: G
authors.lastname: Bradwin
authors.forename: Carolyn
authors.initials: C
authors.lastname: Revta
authors.forename: Julie
authors.initials: J
authors.lastname: Aldridge
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.forename: Edwin
authors.initials: E
authors.lastname: Alyea
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: Robert
authors.initials: R
authors.lastname: Soiffer
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D015415:Biomarkers / Q000097:blood; D019040:E-Selectin / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood* / Q000209:etiology / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D012189:Retrospective Studies; D012307:Risk Factors; D018180:Thrombomodulin / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D015415:Biomarkers; D019040:E-Selectin; C546936:SELE protein, human; C546931:THBD protein, human; D018180:Thrombomodulin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1