Improving Outcomes Assessment in Chronic GVHD

描述（由申请人提供）：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，并且仍然是成功移植的主要障碍之一。在过去的20年里，在理解和改善慢性GVHD的治疗方面取得的进展相对较小，尽管支持性治疗取得了进展，但慢性GVHD诊断后的生存率几乎没有提高。NIH于2004年6月就这一主题召开了一次共识会议，并于最近发表了关于改进研究方法的六篇系列论文。 共识会议认识到缺乏基本的观察数据来指导临床试验的标准。为了满足这一需求，我们建议建立一个多中心、观察性、纵向队列，以改善慢性GVHD的结局评估，具体目标是：（1）验证危险分层的预后因素;以及（2）定义慢性GVHD活动指数的显著变量，该指数预测短期GVHD，（供应商对变化的感知，患者对变化的感知，以及免疫抑制药物的变化）和长期结果（总生存期，停止全身免疫抑制治疗的时间和功能障碍）。这一目标将通过在四个大型移植中心聚集一个大型的慢性GVHD患者现代队列来实现。 将入组约880例慢性GVHD患者（一半为流行病例，一半为偶发病例）。每3-6个月，我们将收集反映疾病活动性的客观和主观指标、对治疗的反应、医生对器官受累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。数据将用于测试已发表的假设和NIH共识会议提出的新建议。我们还将能够提供了解慢性GVHD发病率、表现和治疗反应的现代趋势所需的详细数据。需要这些研究来实施NIH共识会议的建议，促进我们对慢性GVHD的理解，并提高我们进行临床试验的能力。

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.