Infections in Hematopoietic Cell Transplant Recipients

造血细胞移植受者的感染

• 批准号: 7662085
• 负责人: MICHAEL J BOECKH
• 金额: $ 17.81万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-03 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7662085
• 关键词: Address; Affect; Antiviral Agents; Area; Arts; Asses; Award; Biology; Case Report Form; Cell Transplants; Cessation of life; Characteristics; Clinical; Clinical Research; Cohort Analysis; Collection; Communicable Diseases; Communities; Coronavirus; Cytomegalovirus; Data; Data Analyses; Data Collection; Databases; Diagnostic; Disease; Disease Management; Donor Selection; Gastrointestinal Diseases; Genetic; Genetic Markers; Genetic Polymorphism; Genome; Goals; Hematopoietic; Hematopoietic Stem Cell Transplantation; Human; Immunosuppression; Infection; Instruction; Internet; Knowledge; Lead; Low Prevalence; Measures; Medicine; Mentors; Methodology; Molecular; Morbidity - disease rate; Natural Immunity; Outcome; Outcome Study; Patients; Pharmaceutical Preparations; Physicians; Platelet Factor 4; Pneumonia; Polyomavirus; Prevention strategy; Prophylactic treatment; Randomized Controlled Clinical Trials; Rare Diseases; Research; Rhinovirus; Risk; Risk Assessment; Risk Factors; Scientist; Selection Criteria; Stratification; Surveys; Symptoms; Therapeutic Intervention; Time; Training; Translations; Transplant Recipients; Transplantation; Validation; Viral Load result; Virus; Wit; abstracting; base; cohort; design; genome wide association study; genome-wide analysis; high risk; human coronavirus; improved; innovation; insight; mortality; novel; pathogen; patient oriented research; prophylactic; prospective; respiratory; respiratory infection virus; respiratory virus; response; virus genetics

DESCRIPTION (provided by applicant): Patient-oriented research of infections in hematopoietic stem cell transplantation (HCT) provides the opportunity to directly affect outcome of HCT recipients. Infections continue to be a major cause of morbidity and death after HCT. This award will provide protected time for the applicant to mentor trainees in clinical research that is directly related to understanding the biology of infections after HCT. Results will provide the basis for translation into improved management strategies. This proposal will address three areas of transplant infectious diseases: respiratory virus infections, genetics of infections, and factors associated with outcome of infectious diseases. The Specific Aims are: 1. To determine the spectrum virologic chracteristics, and risk factors of recently discovered respiratory viruses after HCT, including human metapneumonovirus, coronaviruses (including (NL63, HKU1), rhinoviruses and bocavirus. Studies of these viruses will be done using a prospective observational cohort of 500 HCT recipients who are undergoing weekly PCR surveillance for 12 viruses and assessment of respiratory symptoms. 2. To determine the impact of donor and recipient innate genetic factors on the risk and outcome of infectious complications following HCT by genome-wide analysis and subsequent validation in separate cohorts. Hole genome data are available for 1500 patient/donor pairs. Associations of polymorphisms with infections will be analyzed and validated in separate cohorts. 3. To conduct outcome studies of invasive infections after NCT. We will evaluate pathogen burden, with CMV viral load as an example, as a variable that determines overall outcome of HCT in the current era of antiviral preemptive therapy. We will also determine factors associated wit the outcome of invasive diseases. Using large databases, we will assess factors associated with response to treatment of CMV gastrointestinal disease and RSV pneumonia (using an internet-based survey administered to transplant centers worldwide). RELEVANCE (See instructions): These aims support an innovative approach toward patient-oriented research in the field of transplant infectious disease by utilizing state-of-the-art methodologies including quantitative molecular diagnostics, whole genome analysis, and internet-based data collection for rare disease. The studies conducted under these aims have a high potential of advancing our knowledge of the spectrum of infectious complications, the genetic basis of diseases, and factors that affect outcome. (End of Abstract)

描述（由申请人提供）：造血干细胞移植（HCT）中感染的以患者为导向的研究为直接影响HCT受体结果的机会提供了机会。感染仍然是HCT后发病和死亡的主要原因。该奖项将为申请人提供临床研究中的导师学员的受保护时间，这与了解HCT后感染的生物学直接相关。结果将为改进的管理策略提供基础。该提案将解决移植感染疾病的三个领域：呼吸道病毒感染，感染的遗传学以及与传染病结果相关的因素。具体目的是：1。确定HCT之后最近发现的呼吸道病毒的频谱病毒学性因素，包括人类元纳莫诺病毒，冠状病毒，冠状病毒（包括（NL63，HKU1），鼻腔病毒和bocavirus和Bocavirus。对这些病毒的研究将在未经前景的情况下进行500 HCT的研究。 12个病毒和呼吸道症状。 NCT后的感染。我们还将确定与侵入性疾病结果相关的因素。使用大数据库，我们将评估与对CMV胃肠道疾病和RSV肺炎治疗的反应相关的因素（使用针对全球移植中心进行的基于Internet的调查）。相关性（请参阅说明）：这些目标通过利用包括定量分子诊断，整个基因组分析和基于Internet的数据收集的罕见疾病的最新方法来支持在移植传染病领域的创新方法。在这些目标下进行的研究具有较高的潜力，可以推进我们对传染病的范围，疾病的遗传基础以及影响预后的因素的了解。 （抽象的结尾）