A Retrospective and Cross- Sectional Study of Hematopoietic Cell Transplantation

严重联合免疫缺陷(SCID)包括一系列致命性遗传疾病，导致 T和B细胞发育和/或功能严重缺陷，使受影响的患者无法 增强对外源病原体的保护性免疫反应。从历史上看，孩子们患有 SCID很少在生命的第一年存活下来，死于严重的感染。SCID的第一种治疗方法是 1968年通过移植来自人类白细胞抗原的骨髓(造血细胞移植)实现的 相容的正常同胞，导致T和B细胞免疫重建。从那时起，更多的 北美700多名SCID患者接受了来自匹配同胞、单倍体相合的HCT治疗 父母，或无血缘关系的成人捐赠者或脐带血。虽然结果总体上是好的，但并不是所有的 患者存活下来，多个患者、捐赠者和移植程序的差异可能是 每例患者的预后。我们已经建立了一个多机构联盟来研究这一大群 患者，目标是确定预后因素和确定最佳治疗方法。在……里面 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 在参与机构接受了HCT。我们将分析患者、供者和移植相关的影响 这些因素对长期结果有影响。这项研究还将提供第一个多中心分析 SCID基因分型对移植结局的影响在具体目标2中，我们将执行横截面 血细胞移植后长期存活的SCID患者的分析，以了解目前T、B和NK细胞的水平 嵌合体和功能，以及在健康、生长和生理和神经认知方面的临床状况 发展。然后，我们将根据回顾中收集的信息来分析这些结果 确定SCID基因、移植类型或其他临床应用是否及程度的研究 变量对患者的长期结果有影响。这些研究将在以下方面提供重要信息 HCT治疗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.