Endothelial 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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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 May 2026.
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