Plasma Biomarkers of Acute Graft Versus Host Disease

急性移植物抗宿主病的血浆生物标志物

• 批准号: 8424381
• 负责人: JAMES L. M. FERRARA
• 金额: $ 20.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424381
• 关键词: Acute Graft Versus Host Disease; Aftercare; Algorithms; Allogeneic Bone Marrow Transplantation; Allogenic; Biological Markers; Clinical; Clinical Trials; Complication; Diagnostic; Diagnostic tests; IL2RA gene; IL8 gene; Laboratories; Measures; Newly Diagnosed; PI3 gene; Patients; Phase II Clinical Trials; Phase III Clinical Trials; Plasma; Randomized; Sampling; Serum; TNFRSF1A gene; Testing; Treatment outcome; Validation; graft vs host disease; hematopoietic cell transplantation; mortality; public health relevance; response; treatment duration; treatment response

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.

描述（由申请人提供）：急性移植物抗宿主病（GVHD）是同种异体造血细胞移植（HCT）的主要限制。目前没有可靠的诊断测试来预测与长期生存相关的治疗结果。我们最近评估了六种先前验证的 GVHD 诊断生物标志物（IL2R？、TNFR1、HGF、IL8、elafin 和 REG3？），以评估它们预测哪些患者会对治疗有反应以及谁将实现长期生存的能力。我们测量了生物标志物浓度通过从参加新诊断急性 GVHD 的多中心、随机 II 期临床试验的 112 名患者在治疗开始时和治疗后第 28 天前瞻性获得的样本中，我们发现了一种使用值的算法。该项目将通过测量最近参加多中心随机阶段的第二组 200 名患者的所有六种生物标志物来验证该算法。针对新诊断的急性 GVHD 的 II 期临床试验还将开发一种新算法，其中包含第七种生物标志物，该生物标志物也可以预测对 GVHD 治疗的反应。该算法将包括治疗开始后第 28 天的治疗反应以及治疗开始后第 180 天的死亡率。