Plasma Biomarkers of Acute Graft Versus Host Disease

描述(申请人提供)：急性移植物抗宿主病(GVHD)是异基因造血细胞移植(HCT)的主要限制因素。目前还没有可靠的诊断测试来预测治疗的结果，这与长期生存相关。我们最近评估了6个先前验证的GVHD诊断生物标记物(IL2R？、TNFR1、HGF、IL8、elafin和REG3？)，以评估它们预测哪些患者对治疗有反应以及哪些患者可以获得长期生存。我们通过对112名参加新诊断的急性移植物抗宿主病的多中心随机II期临床试验的患者在治疗开始时和治疗后第28天预期获得的样本来测量生物标记物的浓度。我们发现了一种算法，它使用所有六个生物标志物的值来预测第28天的治疗反应和发病后第180天的死亡率。该项目将通过在最近参加了新诊断的急性移植物抗宿主病的多中心随机II期临床试验的200名患者中测量所有6个生物标记物来验证该算法。AWE还将开发一种新的算法，包括第七个生物标记物，该标记物也可以预测GVHD的治疗反应。这一算法将包括开始治疗后第28天对治疗的反应以及开始治疗后第180天的死亡率。

DESCRIPTION (provided by applicant): Acute graft-versus-host disease (GVHD) is the primary limitation of allogeneic hematopoietic cell transplantation (HCT). There are currently no reliable diagnostic tests to predict the outcome of treatment, which correlate to long term survival. We have recently evaluated six previously validated diagnostic biomarkers of GVHD (IL2R?, TNFR1, HGF, IL8, elafin, and REG3?, for their ability to predict which patients would respond to therapy and who would achieve long term survival. We measured biomarker concentrations by from samples prospectively obtained at the initiation of treatment and day 28 following treatment in 112 patients who participated in a multicenter, randomized phase II clinical trial for newly diagnosed acute GVHD. We discovered an algorithm using values from all six biomarkers that predicted both day 28 response to treatment and mortality at day 180 from onset. This project will validate that algorithm by measuring all six biomarkers in a second group of 200 patients who patients who have recently participated in a multicenter, randomized phase II clinical trial for newly diagnosed acute GVHD. Awe will also develop a new algorithm by including a seventh biomarker that also predicts for response to treatment for GVHD. This algorithm will include both responses to treatment on day 28 after initiation of treatment as well as mortality at day 180 from the initiation of treatment.