Prognostic Biomarkers for Acute Graft-versus-Host Disease Risk after Cyclophosphamide-Fludarabine Nonmyeloablative Allotransplantation

Five candidate plasma biomarkers (suppression of tumorogenesis 2 [ST2], regenerating islet-derived-3 alpha [REG3 alpha], elafin, tumor necrosis factor receptor 1 [TNFR1], and soluble IL-2 receptor-alpha [sIL2R alpha]) 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 REG3 alpha 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 sIL2R alpha were not associated with aGVHD risk at any of the time points studied. This study identified ST2, REG3 alpha, 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. (C) 2014 American Society for Blood and Marrow Transplantation.