A Retrospective and Cross- Sectional Study of Hematopoietic Cell Transplantation

造血细胞移植的回顾性横断面研究

• 批准号: 8326283
• 负责人: Richard John O'REILLY
• 金额: $ 15.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-12 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326283
• 关键词: Acute; Adult; Affect; Age; Allogenic; Antigens; Autoimmune Diseases; B-Cell Development; B-Lymphocytes; Bone Marrow Transplantation; Cell Transplantation; Cell Transplants; Characteristics; Child; Chimerism; Clinical; Clinical Trials; Cross-Sectional Studies; Defect; Development; Diagnosis; Disease; Donor person; Drug usage; Effectiveness; Elements; Epitopes; Future; Genotype; Goals; Growth; Growth and Development function; Haplotypes; Health; Hematopoietic; Hereditary Disease; Histocompatibility Testing; Immune; Immune response; Immune system; Immunity; Immunologic Deficiency Syndromes; Immunologics; Infection; Inherited; Institution; Instruction; Late Effects; Lead; Life; Long-Term Survivors; Measures; Myelogenous; Natural Killer Cells; Neurocognitive; North America; Outcome; Parents; Patients; Pattern; Population; Prognostic Factor; Prophylactic treatment; Quality of life; Relative (related person); Retrospective Studies; SCID Mice; Severe Combined Immunodeficiency; Severities; Siblings; Specificity; T-Lymphocyte; Therapeutic; Therapeutic Clinical Trial; Time; Transplantation; Umbilical Cord Blood; Variant; chronic graft versus host disease; cohort; design; graft vs host disease; health related quality of life; information gathering; outcome forecast; pathogen; patient population; prevent; prospective; receptor expression; reconstitution; response; transplantation typing

Severe Combined Immune Deficiency (SCID) includes a spectrum of lethal genetic disorders resulting in profound deficiencies of T and B cell development and/or function, which render affected patients incapable of mounting protective immune responses against exogenous pathogens. Historically, children afflicted with SCID rarely survived the first year of life, succumbing to severe infections. The first cure of SCID was achieved in 1968 by transplantation of bone marrow (hematopoietic cell transplant - HCT) from an HLA compatible normal sibling, resulting in reconstitution of both T and B cell immunity. Since that time, more than 700 SCID patients in North America have been treated with HCT from matched siblings, haplo-identical parents, or unrelated adult donors or umbilical cord blood. While outcomes are generally good, not all patients survive and multiple patient-, donor- and transplant procedural differences may underlie the prognosis in each case. We have constructed a multi-institutional consortium to study this large cohort of patients, with the goal of identifying prognostic factors and defining optimal treatment approaches. In Specific Aim 1, we will perform a retrospective analysis of patients with the different forms of SCID who have received HCT at the participating institutions. We will analyze the impact that patient-, donor-, and transplantrelated factors have on long-term outcome. This study will also provide the first multicenter analysis of the effects of SCID genotype on the outcome of transplant. In Specific Aim 2, we will perform a cross-sectional analysis of long-term survivors after HCT for SCID, to characterize current level of T, B and NK cell chimerism and function, and clinical status in terms of health, growth and both physical and neurocognitive development. We will then analyze these results in relation to information gathered in the retrospective study to determine whether and to what degree SCID genotype, type of transplant applied or other clinical variables contribute to the patient's long-term outcome. These studies will produce important information on the outcomes of HCT for SCID and guide future clinical trials.

严重联合免疫缺陷 (SCID) 包括一系列致命的遗传性疾病，导致 T 和 B 细胞发育和/或功能的严重缺陷，导致受影响的患者丧失能力 增强针对外源病原体的保护性免疫反应。历史上，患有此病的儿童 SCID 很少能在出生后第一年存活下来，并死于严重感染。 SCID 的第一个治愈方法是 1968 年通过 HLA 骨髓移植（造血细胞移植 - HCT）实现 兼容的正常兄弟姐妹，导致 T 细胞和 B 细胞免疫的重建。从那时起，更多 北美超过 700 名 SCID 患者接受了匹配兄弟姐妹的 HCT 治疗，单倍体相同 父母，或无关的成年捐赠者或脐带血。虽然结果总体良好，但并非全部 患者存活下来，患者、供体和移植程序的多种差异可能是造成这种情况的原因 每个病例的预后。我们建立了一个多机构联盟来研究这一大群 患者，目的是确定预后因素并确定最佳治疗方法。在 具体目标 1，我们将对患有不同形式 SCID 的患者进行回顾性分析 在参与机构接受了 HCT。我们将分析患者、捐赠者和移植相关的影响 因素影响长期结果。这项研究还将提供首次多中心分析 SCID 基因型对移植结果的影响。在具体目标 2 中，我们将进行横断面分析 对 HCT 后的长期幸存者进行 SCID 分析，以表征 T、B 和 NK 细胞的当前水平 嵌合状态和功能，以及健康、生长、身体和神经认知方面的临床状态 发展。然后，我们将根据回顾中收集的信息来分析这些结果 研究以确定 SCID 基因型是否以及程度、移植类型或其他临床情况 变量有助于患者的长期结果。这些研究将产生重要信息 HCT 治疗 SCID 的结果并指导未来的临床试验。