title: Prognostic biomarkers for acute graft-versus-host disease risk after cyclophosphamide-fludarabine nonmyeloablative allotransplantation.
abstract: Five candidate plasma biomarkers (suppression of tumorogenesis 2 [ST2], regenerating islet-derived-3α [REG3α], elafin, tumor necrosis factor receptor 1 [TNFR1], and soluble IL-2 receptor-alpha [sIL2Rα]) were measured at specific time points after cyclophosphamide/fludarabine-based nonmyeloablative allotransplantation (NMAT) in patients who did or did not develop acute graft-versus-host disease (aGVHD). Plasma samples from 34 patients were analyzed at days +7, +14, +21, and +30. At a median follow-up of 358 days, 17 patients had experienced aGVHD with a median time to onset at day +36. Risk of aGVHD was associated with elevated plasma ST2 concentrations at day +7 (c-statistic = .72, P = .03), day +14 (c-statistic = .74, P = .02), and day +21 (c-statistic = .75, P = .02); elevated plasma REG3α concentrations at day +14 (c-statistic = .73, P = .03), day +21 (c-statistic = .76, P = .01), and day +30 (c-statistic = .73, P = .03); and elevated elafin at day +14 (c-statistic = .71, P = .04). Plasma concentrations of TNFR1 and sIL2Rα were not associated with aGVHD risk at any of the time points studied. This study identified ST2, REG3α, and elafin as prognostic biomarkers to evaluate risk of aGVHD after cyclophosphamide/fludarabine-based NMAT. These results need to be confirmed in an independent validation cohort.
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine and the Melvin and Bren Simon Cancer Center, Indianapolis, Indiana; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Nelson
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine and the Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Muhammad Rizwan
authors.initials: MR
authors.lastname: Khawaja
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Perkins
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Elmore
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Christen L
authors.initials: CL
authors.lastname: Mumaw
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine and the Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Christie
authors.initials: C
authors.lastname: Orschell
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine and the Melvin and Bren Simon Cancer Center, Indianapolis, Indiana; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: sophpacz@iu.edu.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000208:Acute Disease; D014408:Biomarkers, Tumor / Q000097:blood*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Acute graft-versus-host-disease; Biomarkers; Nonmyeloablative allotransplantation