Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplants (HCT)

同种异体造血细胞移植（HCT）的受者遭受独特的免疫介导的疾病。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同种异体移植排斥反应，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受者发生免疫介导的疾病，导致与治疗相关的高发病率和死亡率。两种最常见的免疫介导并发症是异质性综合征，统称为“急性移植物抗宿主病（GVHD）”和“慢性移植物抗宿主病”。慢性GVHD是同种异体HCT术后2年以上非复发性死亡的主要原因。GVHD的不同综合征可能具有不同的致病机制。罕见病临床研究联盟（RDCRC）的目标是促进我们对这些疾病的理解和治疗。

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.