Improving Outcomes Assessment in Chronic GVHD

描述(申请人提供)：慢性移植物抗宿主病(GVHD)是输注异基因造血干细胞后最具破坏性的长期并发症之一，它仍然是成功移植的主要障碍之一。在过去的20年里，在了解和改进慢性GVHD的治疗方面取得的进展相对较少，尽管支持性护理取得了进展，但慢性GVHD诊断后的存活率几乎没有改善。美国国立卫生研究院于2004年6月召开了一次关于这一主题的协商一致会议，最近在六篇系列论文中发表了关于改进研究方法的建议。 共识会议认识到，缺乏指导临床试验标准的基本观测数据。为了满足这一需求，我们建议建立一个多中心、观察性的纵向队列，以改善慢性GVHD的预后评估，具体目标是：(1)验证风险分层的预后因素；(2)为预测短期(提供者对变化的感知、患者对变化的感知、免疫抑制药物的变化)和长期结果(总体存活率、停止全身免疫抑制治疗的时间和功能损害)的慢性GVHD活动指数定义重要变量。这一目标将通过在四个大型移植中心聚集一大批现代慢性移植物抗宿主病患者来实现。 大约880名慢性移植物抗宿主病患者(一半是流行病例，一半是偶发病例)将被纳入。每隔3-6个月，我们将收集反映疾病活动、治疗反应的客观和主观指标、医生对器官损害的详细评估，以及患者对症状、功能状态和生活质量的自我评估。数据将被用来检验发表的假说和来自NIH共识会议的新建议。我们还将能够提供所需的详细数据，以了解慢性移植物抗宿主病的发病率、表现和治疗反应的现代趋势。这些研究对于落实NIH共识会议的建议、增进我们对慢性GVHD的理解以及增强我们进行临床试验的能力是必要的。

DESCRIPTION (provided by applicant): Chronic graft-versus-host disease (GVHD) is one of the most devastating long-term complications after infusion of allogeneic hematopoietic stem cells, and it remains one of the major barriers to successful transplantation. Relatively little progress has been made in understanding and improving treatments for chronic GVHD over the last 20 years, and the survival rate after diagnosis of chronic GVHD has barely improved despite advances in supportive care. The NIH convened a Consensus Conference on this topic in June 2004 and recently published its recommendations on improving research methods in a series of six papers. The Consensus Conference recognized a lack of basic observational data to guide standards for clinical trials. In order to address this need, we propose to establish a multi-center, observational, longitudinal cohort in order to improve outcomes assessment in chronic GVHD with the specific aims of (1) validating prognostic factors for risk stratification; and (2) defining significant variables for a chronic GVHD activity index that predicts short-term (provider perception of change, patient perception of change, and changes in immunosuppressive medications) and longer-term outcomes (overall survival, time to discontinuation of systemic immunosuppressive therapy, and functional impairments). This goal will be accomplished by assembling a large modern cohort of people with chronic GVHD at four large transplant centers. Approximately 880 people (half prevalent cases, half incident cases) with chronic GVHD will be enrolled. Every 3-6 months we will collect both objective and subjective measures reflecting disease activity, response to therapy, detailed physician assessments about organ involvement, and patient self-assessments about symptoms, functional status, and quality of life. Data will be used to test published hypotheses and the new recommendations emanating from the NIH Consensus conference. We will also be able to provide the detailed data needed to understand modern trends in chronic GVHD incidence, manifestations, and response to treatment. These studies are needed to operationalize the recommendations of the NIH Consensus conference, advance our understanding of chronic GVHD, and enhance our ability to conduct clinical trials.