EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis
EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis
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DOI：
10.1016/s2352-3026(17)30108-4
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发表时间：
2017-09-01
影响因子：
24.7
通讯作者：
Penack, Olaf
中科院分区：
文献类型：
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作者：
Luft, Thomas;Benner, Axel;Penack, Olaf
背景：血管内皮功能障碍与异基因干细胞移植后激素难治性移植物抗宿主病(GVHD)有关。我们旨在评估简单的公式-乳酸脱氢酶(U/L)×肌酐(mg/dL)/血小板(10(9)个/L)-被称为内皮激活和应激指数(EASIX)是否对预测异基因干细胞移植后急性移植物抗宿主病患者的死亡有价值。方法回顾分析连续接受异基因干细胞移植的急性移植物抗宿主病患者的一个训练队列和三个验证队列(德国和美国)。主要终点是在急性移植物抗宿主病(EASIX-GVHD)发作时对总存活率的预测。通过计算预测误差(Brier积分)和一致性指数，我们在三个独立的队列中验证了EASIX-GVHD对总生存率和无复发死亡率的预测能力。在急性GVHD患者的总队列中(n=311)，EASIX-GVHD在单变量和多变量模型中预测总生存率(单变量分析，风险比[HR]增加一倍，危险比[HR]增加1.16%，95%CI1.12-1.20，p=0.0004)。然而，在接受清髓性调节的患者亚群(n=72)中，EASIX-GVHD并不能预测总存活率，这可能归因于GVHD发病时的血小板减少(清髓性调节的每名L有73×10(9)个细胞[IQR29.75-180.00]，而强度降低的条件下每名L有160x10(9)个细胞；p
Background 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) x 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.Methods 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.Findings 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 x 10(9) cells per L [IQR 29.75-180.00] for myeloablative conditioning vs 160 x 10(9) cells per L [90.0-250.5] for reduced-intensity conditioning; p