GRAFT REJECTION

移植物排斥反应

• 批准号: 6557776
• 负责人: IAN K MCNIECE
• 金额: $ 15.53万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-08 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6557776
• 关键词: T lymphocyte; bone marrow transplantation; cell cell interaction; cell mediated lymphocytolysis test; clinical research; cytotoxic T lymphocyte; disease /disorder proneness /risk; dyserythropoietic anemia; flow cytometry; hematopoietic stem cells; homologous transplantation; human subject; patient oriented research; stem cell transplantation; stem cells; technology /technique development; tissue /cell culture; transplant rejection

DESCRIPTION (provided by applicant): Non-myeloablative transplants are being used increasingly for a number of diseases, including Non Hodgkins lymphoma, Hodgkin's disease, myeloma, acute leukemia, chronic lymphoytic leukemia (CLL) and chronic myelogenous leukemia (CML). A reduction in toxicity compared to fully myeloabative allogeneic stem cell transplantation is stimulating the use of this strategy particularly for older patients. Donor engraftment is achieved in the majority of patients, however, a significant number of patients, particularly those with myelodisplastic syndrome (MDS) experience secondary loss of donor engraftment. This can be fatal for some patients due to the prolonged pancytopenia that follows. There are several possibilities for the loss of donor engraftment; 1) donor graft rejection by recipient T cells, 2) late donor graft failure due to insufficient stem cells in the graft, or 3) dominance of recipient stem cells due to competitive repopulation. In allogeneic transplants to support high dose chemotherapy, graft failure/graft rejection occurs early after transplant within the first month, however, for patients that achieve early donor engraftment secondary graft failure/graft rejection is rare and only occurs in less than 5% of patients [1,2]. In contrast, nearly a 100% of patients receiving mini-allogeneic transplants achieve donor engraftment within 2 months of transplant. Graft failure/graft rejection occurs at 2 to 4 months post transplant in approximately 15% of mini-allogeneic recipients. We hypothesize that loss of donor grafts in non-myeloablative stem cell transplant (NST) recipients can occur due to rejection of the donor cells by recipient T cells and/or low numbers of donor stem cells in the graft resulting in secondary graft failure. The aim of this proposal is to develop methods to evaluate graft rejection and determine the mechanisms responsible for late donor graft failure in recipients of NST.

描述（由申请人提供）：多种疾病正在越来越多地用于多种疾病，包括非霍奇金斯淋巴瘤，霍奇金病，骨髓瘤，急性白血病，慢性淋巴白血病（CLL）和慢性髓质白血病（CML）。与完全骨髓性的同种异体干细胞移植相比，毒性降低是刺激这种策略的使用，尤其是对于老年患者。大多数患者都可以实现供体植入，但是，大量患者，尤其是患有骨髓增生综合征（MDS）的患者，经历了供体植入的继发性丧失。由于随后的全年多年症，这对某些患者可能是致命的。失去捐助者的可能性有几种可能性。 1）受体T细胞的供体移植排斥反应，2）由于移植物中干细胞不足而导致的晚期供体移植失败，或3）由于竞争性重料而引起的受体干细胞的优势。但是，在同种异体移植以支持高剂量化学疗法的同种异体移植物中，第一个月内移植后早些时候发生移植失败/移植物排斥反应，对于实现早期供体植入次要的次要移植衰竭/移植物排斥的患者很少，仅在不到5％的患者中发生[1,2]。相比之下，几乎100％接受迷你化学移植的患者在移植后2个月内就可以养成供体植入。在移植后2至4个月发生移植失败/移植物排斥反应，大约15％的微型合成受体。我们假设由于受体T细胞对供体细胞的排斥反应和/或移植物中供体数量少的供体干细胞导致继发性移植物失败，因此可能发生非毛囊干细胞移植（NST）受体中供体移植物的丧失。该提案的目的是开发评估移植物排斥的方法，并确定导致NST接受者晚期供体移植失败的机制。