Allogeneic Hematopoietic Cell Transplantation for Nonmalignant Disorders

在我们继续努力治疗其他致命疾病的患者时，将追求两个总体目标。 非恶性血液病的异基因造血细胞移植。一是降低 方案相关毒性和移植相关并发症，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供体的选择范围， 通过包括无关的脐带血和HLA-半相合的骨髓细胞的移植物的无关的志愿者。 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符合所提出的方案， 我们已经采取了两个步骤。第一个是将其他学术中心作为参与者， 问题研究第二，对于涉及免疫缺陷疾病患者的协议很重要， 建立密切的合作，与关键成员的儿科免疫组在大学 华盛顿/儿童医院和地区医疗中心，他们看到和研究许多这样的病人。 该项目下的研究与患者的造血细胞移植相关 血红蛋白病，如镰状细胞病和重型地中海贫血，自身免疫性疾病， 患有恶性疾病，包括骨髓增生异常综合征，在本补助金的项目4下进行研究。 此外，造血细胞移植方案，被发现是既有效又安全的患者 与血液病，可能最终在治疗实体器官移植受体， 例如肾或肺。在这种情况下，同时或之前从肾或肺进行造血移植， 供体将为实体器官移植提供免疫学“平台”，这将是无限期的。 不需要终身免疫抑制。

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.