Prospective external validation of biomarkers to predict acute graft-versus-host disease severity

前瞻性外部验证生物标志物以预测急性移植物抗宿主病的严重程度

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作者:Marie Robin, Raphael Porcher, David Michonneau, Laetitia Taurines, Flore Sicre de Fontbrune, Aliénor Xhaard, Bastien Oriano, Aurélien Sutra Del Galy, Régis Peffault de Latour, Gérard Socié, Marie-Hélène Schlageter

Abstract

Acute graft-versus-host disease (GVHD) is still the major contributor to comorbidities and mortality after allogeneic hematopoietic stem cell transplantation. The use of plasmatic biomarkers to predict early outcomes has been advocated in the past decade. The purpose of this prospective noninterventional study was to test the ability of panels including 7 biomarkers (Elafin, HGF, IL2RA, IL8, REG3, ST2, and TNFRI), to predict day 28 (D28) complete response to steroid, D180 overall survival, and D180 nonrelapse mortality (NRM). Using previous algorithms developed by the Ann Arbor/MAGIC consortium, 204 patients with acute GVHD were prospectively included and biomarkers were measured at GVHD onset for all of them. Initial GVHD grade and bilirubin level were significantly associated with all those outcomes. After adjustment on clinical variables, biomarkers were associated with survival and NRM. In addition to clinical variables, biomarkers slightly improved the prediction of overall survival and NRM (concordance and net reclassification indexes). The potential benefit of adding biomarkers panel to clinical parameters was also investigated by decision curve analyses. The benefit of adding biomarkers to clinical parameters was however marginal for the D28 nonresponse and mortality endpoints.

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