Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplants (HCT)

异基因造血细胞移植（HCT）的接受者患有独特的免疫介导的病症。虽然这些疾病的成分类似于已知的自身免疫综合征或实体器官移植排斥反应，但其潜在的免疫学特征尚不清楚。2007年，在美国进行了大约9，500例同种异体HCT，主要用于治疗罕见疾病，如白血病，淋巴瘤，多发性骨髓瘤和其他血液病。大约50%的同种异体HCT接受者发生免疫介导的疾病，导致高治疗相关的发病率和死亡率。两种最常见的免疫介导的并发症是异质性综合征，统称为"急性移植物抗宿主病（GVHD）"和"慢性GVHD"。"慢性GVHD是异基因HCT后2年以上非复发死亡的主要原因。GVHD中的不同综合征可能具有不同的致病机制。这个罕见疾病临床研究联盟（RDCRC）的目标是促进我们对这些疾病的理解和治疗。 项目1是一项综合生物学研究的观察性研究。患者将在HCT前入组，并前瞻性随访免疫介导疾病的发生。被诊断为慢性GVHD的患者将通过联盟目前资助的U01研究“改善慢性GVHD的结局评估”（PI：Stephanie Lee，CA 118953 - 01A1，2007 - 2012）进行深入研究。项目2和试点提出了三项临床试验，目标是公认但了解甚少的综合征，发病率/死亡率特别高：皮肤硬化症，闭塞性细支气管炎综合征和晚期急性GVHD。新的靶向治疗和广泛的生物学分析将帮助我们更好地了解和治疗这些疾病。 RDCRC的组成部分还侧重于培训，教育，外展和与罕见疾病网络其他成员的互动。我们与三个患者倡导组织合作，接触患者，家庭和医生。

Recipients of allogeneic hematopoietic cell transplants (HCT) suffer from unique immune mediated disorders. Although components of these disorders resemble known autoimmune syndromes or solid organ allograft rejection, the underlying immunology is poorly characterized. In 2007, approximately 9,500 allogeneic HCTs were performed in the United States, primarily for the treatment of rare diseases such as leukemia, lymphoma, multiple myeloma and other hematologic diseases. Approximately 50% of allogeneic HCT recipients develop immune mediated disorders resulting in high treatment-related morbidity and mortality. The two most common immune mediated complications are heterogeneous syndromes collectively called "acute graft-versus-host disease (GVHD)" and "chronic GVHD." Chronic GVHD is the leading cause of non-relapse death more than 2 years after allogeneic HCT. The different syndromes within GVHD are likely to have different pathogenic mechanisms. The goal of this Rare Diseases Clinical Research Consortium (RDCRC) is to advance our understanding and treatment of these disorders. Project 1 is an observational study with integrated biologic investigations. Patients will be enrolled prior to HCT and followed prospectively for the development of immune mediated disorders. Patients who are diagnosed with chronic GVHD will then be intensively studied through the Consortium's currently funded U01 study, "Improving Outcomes Assessment in Chronic GVHD," (PI: Stephanie Lee, CA118953-01A1, 2007- 2012). Project 2 and the Pilots propose three clinical trials targeting well-recognized but poorly understood syndromes with particularly high morbidity/mortality: cutaneous sclerosis, bronchiolitis obliterans syndrome and late acute GVHD. Novel targeted therapies and extensive biologic analysis will help us better understand and treat these disorders. Components of the RDCRC also focus on training, education, outreach and interaction with other members of the Rare Diseases Network. We collaborate with three patient advocacy organizations to reach out to patients, families, and physicians.