Stem Cell Transplantation

干细胞移植

• 批准号: 7294710
• 负责人: Rainer F. Storb
• 金额: $ 16.15万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294710
• 关键词: FK506; aplastic anemia; artificial immunosuppression; blood donor; bone marrow transplantation; clinical trial phase II; congenital aplastic anemia; cord blood; cyclophosphamide; fludarabine; genetic disorder; graft versus host disease; hematopoietic stem cells; hematopoietic tissue transplantation; homologous transplantation; human subject; human therapy evaluation; monoclonal antibody; mycophenolate mofetil; patient oriented research; stem cell transplantation; transplant rejection

Two overall objectives will be pursued in our continued efforts to treat patients with otherwise fatal nonmalignant hematologic diseases by allogeneic hematopoietic cell transplantation. One is to reduce regimen-related toxicities and transplant-related complications, including graft rejection and graft-vs-host disease. The other is to broaden the choice of hematopoietic cell donors beyond HLA-matched relatives and unrelated volunteers by including grafts of unrelated cord blood and HLA-haploidentical marrow cells. Nonmalignant disorders include three distinct disease entities, aplastic anemia. Fanconi anemia, and inherited diseases of the hematopoietic and immune systems. In order to assure accrual of patients with these relatively infrequent diseases to the proposed protocols, we have taken two steps. The first has been to include other academic centers as participants in the studies. The second, important for protocols involving patients with immunodeficiency diseases, has been to establish close collaborations with key members of the Pediatric Immunology group at the University of Washington/Children's Hospital and Regional Medical Center, who see and study many of these patients. The studies proposed under this Project have relevance for hematopoietic cell transplantation in patients with hemoglobinopathies, such as sickle cell disease and thalassemia major, autoimmune diseases, and those with malignant diseases, including myelodysplastic syndromes studied under Project 4 of this grant. Also, hematopoietic cell transplantation protocols, that are found to be both effective and safe for patients with hematologic diseases, might eventually be of interest in the treatment of recipients of solid organ grafts, e.g. kidney or lung. In that setting, a concurrent or preceding hematopoietic graft from the kidney or lung donor would provide an immunologic "platform" for the solid organ graft, which would be indefinitely accepted without the need for lifelong immunosuppression.

在我们继续努力治疗患有其他致命疾病的患者时，我们将追求两个总体目标 通过同种异体造血细胞移植治疗非恶性血液疾病。一是减少 治疗相关的毒性和移植相关的并发症，包括移植物排斥和移植物抗宿主 疾病。另一个是扩大造血细胞捐献者的选择范围，超越HLA匹配的亲属和 通过移植无关的脐带血和 HLA-半相合骨髓细胞来治疗无关的志愿者。 非恶性疾病包括三种不同的疾病实体：再生障碍性贫血。范可尼贫血，以及 造血和免疫系统的遗传性疾病。 为了确保患有这些相对罕见疾病的患者能够接受拟议的方案， 我们采取了两个步骤。第一个是将其他学术中心纳入其中 研究。第二个对于涉及免疫缺陷疾病患者的方案很重要，是 与英国大学儿科免疫学小组的主要成员建立密切合作 华盛顿/儿童医院和地区医疗中心，他们收治并研究了许多此类患者。 该项目提出的研究与患者的造血细胞移植相关 患有血红蛋白病，例如镰状细胞病和重型地中海贫血、自身免疫性疾病，以及 患有恶性疾病的患者，包括本拨款项目 4 下研究的骨髓增生异常综合征。 此外，造血细胞移植方案被发现对患者既有效又安全 患有血液系统疾病，最终可能会对实体器官移植受者的治疗产生兴趣， 例如肾或肺。在这种情况下，同时或之前的肾脏或肺造血移植 捐赠者将为实体器官移植物提供免疫“平台”，该平台将无限期地存在 无需终生免疫抑制即可接受。