Hematopopietic Stem Cell Transplantation

项目1的总体目标是确定成功同种异体造血细胞的遗传障碍 移植（HCT）。来自无关供体的HCT可以治疗血液疾病。完整和精确的供体 HLA配型与上级移植结果相关。然而，移植物抗宿主病的风险 与同胞供体移植相比，死亡率仍然增加。此外，20- 40%的患者 开始搜索的人无法识别合适的匹配捐赠者。选择最佳错配供体的标准 是不明确的。最近，关于KIR受体的新信息表明HLA-KIR的重要性 HCT后同种异体反应的相互作用。项目1的长期目标是提高可用性， 通过优化供体遗传选择来提高HCT的安全性和有效性。具体目标是：1）确定 通过使用HLA不匹配的供者可以增加无关HCT可用性的程度 通过鉴定允许的错配; 2）鉴定与移植相关的新的MHC驻留基因 3）确定HLA-KIR相互作用是否改变移植后并发症的风险。塞林 实现这些目标将扩大无关HCT治疗血液疾病的适用性。

The overall goal of Project 1 is to define the genetic barriers to successful allogeneic hematopoietic cell transplantation (HCT). HCT from unrelated donors can cure blood disorders. Complete and precise donor HLA matching is associated with superior transplant outcome. However, risks of graft-versus-hostdisease and mortality are still increased compared to sibling donor transplantation. Furthermore, 20- 40% ofpatients who start a search fail to identify suitably matched donors. Criteria for selecting optimal mismatched donors are ill-defined. Recently, new information on,KIR receptors demonstrates the importance of HLA-KIR interactions in alloresponses after HCT. The long-term objectives of Project 1 are to improve theavailability, safety and efficacy of HCT by optimizing donor genetic selection. The specific aims are to: 1) define the extent to which availability of unrelated HCT can be increased through the use of HLA mismatcheddonors by identifying permissible mismatches; 2) identify new MHC-resident genes associated with transplant outcome, and 3) determine if HLA-KIR interactions modify risk of post-transplant complications. Successin achieving these goals will broaden the applicability of unrelated HCT to the treatment of blood disorders.