Longitudinal Study of Immune Mediated Disorders After Allogeneic HCT

同种异体 HCT 后免疫介导疾病的纵向研究

• 批准号: 7934861
• 负责人: STEPHANIE J LEE
• 金额: $ 36.47万
• 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: 2009-09-25 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934861
• 关键词: Accounting; Acute; Address; Affect; Agreement; Allogenic; Applications Grants; Autoimmunity; Autologous; Biological Markers; Biostatistical Methods; Blood donor; Bone Marrow; Bronchiolitis Obliterans; CSF3 gene; Cell Transplantation; Cell Transplants; Cells; Characteristics; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Design; Clinical assessments; Collection; Commit; Complex; Consensus; Cutaneous; Data; Development; Diagnosis; Diagnostic; Disease; Dose; Enrollment; Ensure; Functional disorder; Funding; Grant; Hematologic Neoplasms; Hematological Disease; Hematopoiesis; Hematopoietic; Human; Immune; Immunity; Immunologics; Incidence; Infection; Infusion procedures; Institution; Knowledge; Lead; Life; Longitudinal Studies; Malignant Neoplasms; Measures; Mediating; Medical; Modeling; Morbidity - disease rate; Multiple Myeloma; Mus; Myelodysplastic/Myeloproliferative Disease; Observational Study; Outcome; Outcome Assessment; Paper; Pathology; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Population; Procedures; Proteins; Proteomics; Publishing; Radiation; Rare Diseases; Recurrence; Relative (related person); Research; Resources; Sampling; Sclerosis; Severities; Specimen; Staging; Stem cells; Stratification; Supportive care; Syndrome; Therapeutic Studies; Time; Translating; Transplantation; Umbilical Cord Blood; Urine; base; career; chemotherapy; clinically relevant; cohort; cytokine; data integration; disease diagnosis; graft vs host disease; high risk; improved; interest; leukemia/lymphoma; mortality; neoplastic cell; outcome forecast; patient population; peripheral blood; prevent; prospective; prototype; reconstitution; response; success; symposium; tool; treatment response

Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for many hematologic diseases, but development of serious immune mediated disorders after transplantation limits greater success. Although some immune mediated disorders are very rare (< 1%), others such as acute and chronic grafl-versus-host disease (GVHD) are more common (30-50%) and cause high morbidity and mortality. Project 1 is a longitudinal study with the aim of better characterizing the incidence, characteristics, and outcomes of these disorders. We particularly focus on three syndromes with high morbidity and mortality: cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS) and persistent, recurrent or late-onset acute GVHD (late acute GVHD). These syndromes have distinct clinical characteristics and respond poorly to currently available therapies. Based on our current knowledge about potential pathophysiology and response to treatments, we propose biomarker studies and clinical trials of targeted agents elsewhere in the grant proposal. Project 1 will enroll approximately 1000 patients before allogenic HCT who will be followed for two years to collect detailed data about any immune mediated disorders of interest that arise. In addition, research samples will be obtained to provide longitudinal biologic material on affected cases and samples from controls. We will use a subset of these research samples to validate and extend three biomarker models: the Ferrara model of 4 proteins associated with early acute GVHD, the Schultz model of 4 biomarkers associated with chronic GVHD, and the Weissinger urine proteomic patterns associated with acute and chronic GVHD. Since the criteria for positive and negative samples have been determined, we will be able to select purely informative the models. Project 1 is synergistic but not overlapping with a U01 funded observational trial limited to patients with chronic GVHD (2007-2012)

异基因造血细胞移植（HCT）是治疗许多血液病的有效方法， 但是移植后严重的免疫介导的疾病的发展限制了更大的成功。虽然 一些免疫介导的疾病是非常罕见的（< 1%），其他的如急性和慢性移植物抗宿主 移植物抗宿主病（GVHD）更为常见（30-50%），并导致高发病率和死亡率。项目1是 纵向研究，旨在更好地描述这些疾病的发病率，特征和结局。我们特别关注三种发病率和死亡率高的综合征：皮肤硬化症、闭塞性细支气管炎综合征（BOS）和持续性、复发性或迟发性急性GVHD（晚期急性GVHD）。这些综合征具有独特的临床特征，对目前可用的治疗反应不佳。基于我们目前对潜在的病理生理学和治疗反应的了解，我们建议在拨款提案的其他地方进行生物标志物研究和靶向药物的临床试验。 项目1将在同种异体HCT前入组约1000例患者，随访2年，以收集有关出现的任何免疫介导疾病的详细数据。此外，将获得研究样本，以提供受影响病例和对照样本的纵向生物材料。我们将使用这些研究样本的子集来验证和扩展三种生物标志物模型：与早期急性GVHD相关的4种蛋白质的费拉拉模型，与慢性GVHD相关的4种生物标志物的Schultz模型，以及与急性和慢性GVHD相关的Weissinger尿蛋白质组学模式。由于阳性和阴性样本的标准已经确定，我们将能够选择纯粹的信息模型。 项目1与U 01资助的仅限于慢性GVHD患者的观察性试验（2007-2012）具有协同作用，但不重叠