A Retrospective and Cross- Sectional Study of Hematopoietic Cell Transplantation

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，使受影响的患者不能 对外源性病原体的保护性免疫反应。从历史上看， 严重联合免疫缺陷症患者很少能在出生后的第一年内存活下来，最终死于严重的感染。第一个治愈SCID的方法是 1968年通过移植来自HLA的骨髓（造血细胞移植- HCT）实现 相容的正常同胞，导致T和B细胞免疫的重建。从那时起，更多 在北美，超过700名SCID患者已经用来自匹配的兄弟姐妹的HCT治疗， 父母，或无关的成年供体或脐带血。虽然结果总体上是好的，但并非所有 患者存活和多个患者，供体和移植程序的差异可能是 每一个病例的预后我们建立了一个多机构联盟来研究这一庞大的队列， 患者，目的是确定预后因素和确定最佳治疗方法。在 具体目标1，我们将对患有不同形式的SCID的患者进行回顾性分析， 在参与机构接受HCT。我们将分析患者、捐赠者和移植相关的影响， 影响长期结果的因素。这项研究还将提供第一个多中心分析， SCID基因型对移植结果的影响。在具体目标2中，我们将执行横截面 分析SCID HCT后的长期存活者，以表征T、B和NK细胞的当前水平 嵌合体和功能，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分析这些结果 研究，以确定是否和在何种程度上SCID基因型，移植类型或其他临床应用 变量对患者的长期结果有影响。这些研究将提供重要信息， HCT用于SCID的结果，并指导未来的临床试验。

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.