DISCIS Study

DISCIS 研究

• 批准号: 8950245
• 负责人: Brent R Logan
• 金额: $ 13.18万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8950245
• 关键词: Accounting; Acute Graft Versus Host Disease; Address; Allogenic; Area; Attention; Benchmarking; Biological Markers; Blood; Bone Marrow; Bone Marrow Transplantation; Cells; Cessation of life; Characteristics; Clinical; Clinical Trials; Clinical Trials Network; Data; Data Analyses; Data Set; Development; Diagnosis; Disease; Education; Freedom; Funding Opportunities; Future; Gender; Goals; Health; Immune; Immune Tolerance; Immune response; Immunologics; Immunosuppression; Incidence; Injury; Intervention Trial; Investigation; Judgment; Malignant Neoplasms; Marrow; Mission; Modeling; Morbidity - disease rate; Organ; Outcome; Patients; Pharmaceutical Preparations; Prevention; Probability; Procedures; Prophylactic treatment; Recurrence; Relapse; Research; Resolution; Risk; Sentinel; Severities; Siblings; Solutions; Syndrome; Techniques; Time; Transplant Recipients; Transplantation; Variant; base; chronic graft versus host disease; clinical care; clinical practice; clinical predictors; design; experience; follow-up; graft vs host disease; hematopoietic cell transplantation; high risk; innovation; novel; peripheral blood; prospective; public health relevance; randomized trial; success

 DESCRIPTION (provided by applicant): Immunologic tolerance after allogeneic hematopoietic cell transplantation (HCT) is operationally defined by complete discontinuation of immune suppression (IS) and the absence of subsequent graft vs. host disease (GVHD). Acute and chronic GVHD, the sentinel manifestations of immunologic injury driven by donor immune cells, result in morbidity and death, and often develop or reoccur after IS discontinuation. Current scientific understanding of tolerance after HCT is limited, and there are no validated clinical or biologic determinants of immune tolerance after HCT. Therefore, current clinical practice of IS discontinuation is empiric, markedly heterogeneous and complicated by GVHD following IS discontinuation. Comprehensive analysis of IS discontinuation after HCT and subsequent risk for GVHD is needed to advance the field. We propose a robust secondary analysis of existing data (total n=827) from two major Blood and Marrow Transplant Clinical Trials Network (CTN) randomized trials (CTN 0201 and 0402) to address this need. Analysis of these data is ideal, as coverage of relevant patient, transplantation, and GVHD variables, as well as long-term follow up data on IS discontinuation and subsequent GVHD is complete. We will employ multi-state modeling to address our research questions, as this technique can accommodate the multiple health states after HCT relevant to this analysis, estimate the probability for each health state a serial time points after HCT, and model the effect of relevant covariates on the outcomes of IS discontinuation and GVHD following IS discontinuation. Our planned analyses will (1) examine which patient, transplant, and GVHD variables are associated with successful IS discontinuation, and (2) determine the incidence of GVHD following IS discontinuation, and investigate predictors of GVHD development after IS discontinuation.

 描述（由应用提供）：同种异体造血细胞移植后的免疫耐受性（HCT）在操作上是通过完全停用免疫抑制（IS）的操作来定义的，并且缺乏随后的移植物与宿主疾病（GVHD）。急性和慢性GVHD是由供体免疫球造成的免疫损伤的前哨表现，导致发病率和死亡，并且在中止后经常发育或重新出现。当前对HCT后耐受性的科学理解受到限制，并且在HCT后没有得到验证的临床或生物学确定免疫耐受性。因此，当前停用的临床实践是经验性的，在以下是GVHD显着异质和复杂的是中断。需要全面分析HCT之后的IS中断和随后的GVHD风险来推进该领域。我们提出了对两个主要的血液和骨髓移植临床试验网络（CTN）随机试验（CTN 0201和0402）的现有数据（总n = 827）的强大次要分析，以满足这一需求。对这些数据的分析是理想的，因为相关患者，移植和GVHD变量的覆盖范围以及长期后续数据是中断的，随后的GVHD已完成。我们将采用多州建模来解决我们的研究问题，因为该技术可以在与此分析相关的HCT之后适应多个健康状态，估算每个健康状态在HCT之后的序列时间点，并建模相关协变量对is is is is is is is of IS的影响和GVHD的影响。我们计划的分析将（1）检查哪种患者，移植和GVHD变量与成功相关的是中断，并且（2）确定GVHD以下的事件是中断的，并研究了中断GVHD的预测指标。