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000128092 1001_ $$aLuft, Thomas$$b0
000128092 245__ $$aEASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis.
000128092 260__ $$aLondon [u.a.]$$bElsevier$$c2017
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000128092 520__ $$aEndothelial dysfunction links thrombotic microangiopathy to steroid-refractory graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation. We aimed to assess if the simple formula-lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (10(9) cells per L)-termed the Endothelial Activation and Stress Index (EASIX), might be valuable for the prediction of death in patients with acute GVHD after allogeneic stem-cell transplantation.For this retrospective analysis, we analysed a training cohort (in Germany) and three validation cohorts (in Germany and the USA) of patients with acute GVHD who had received consecutive allogeneic stem-cell transplantation. The primary endpoint was prediction of overall survival when measured at acute GVHD onset (EASIX-GVHD). We validated the prognostic strength of EASIX-GVHD for overall survival and non-relapse mortality in the three independent cohorts by calculating the prediction error (integrated Brier score), and concordance index.In the total cohort of patients with acute GVHD (n=311), EASIX-GVHD predicted overall survival in univariable and multivariable models (univariate analysis, hazard ratio [HR] for a one-fold increase 1·16, 95% CI 1·12-1·20, p=0·0004). However, in the subpopulation of patients with myeloablative conditioning (n=72), EASIX-GVHD did not predict overall survival, which is probably attributable to thrombocytopenia at GVHD onset (73 × 10(9) cells per L [IQR 29·75-180·00] for myeloablative conditioning vs 160 × 10(9) cells per L [90·0-250·5] for reduced-intensity conditioning; p<0·0001). In patients who received reduced-intensity conditioning (n=239), EASIX-GVHD was a strong predictor of overall survival (HR for a two-fold change of 1·23, 95% CI 1·13-1·34; p<0·0001) and non-relapse mortality (cause-specific HR for a two-fold change of 1·24, 1·12-1·38; p<0·0001). Model validation for prediction of overall survival and non-relapse mortality by EASIX-GVHD was successful in two independent cohorts of adult patients with reduced-intensity conditioning (n=141, n=173) and in a cohort with mainly paediatric patients (n=89).In patients with reduced-intensity conditioning, EASIX-GVHD is a powerful predictor of survival after GVHD. EASIX-GVHD could be the future basis for development of risk-adapted GVHD treatment strategies.There was no external funding source for this study.
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000128092 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b1$$udkfz
000128092 7001_ $$aJodele, Sonata$$b2
000128092 7001_ $$aDandoy, Christopher E$$b3
000128092 7001_ $$aStorb, Rainer$$b4
000128092 7001_ $$aGooley, Ted$$b5
000128092 7001_ $$aSandmaier, Brenda M$$b6
000128092 7001_ $$0P:(DE-He78)ecb33fb615e08035fdcefcaebfdff8f0$$aBecker, Natalia$$b7$$udkfz
000128092 7001_ $$aRadujkovic, Aleksandar$$b8
000128092 7001_ $$aDreger, Peter$$b9
000128092 7001_ $$aPenack, Olaf$$b10
000128092 773__ $$0PERI:(DE-600)2802056-X$$a10.1016/S2352-3026(17)30108-4$$gVol. 4, no. 9, p. e414 - e423$$n9$$pe414 - e423$$tThe @lancet <London> / Haematology$$v4$$x2352-3026$$y2017
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