Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplants (HCT)

异基因造血细胞移植(HCT)的受体患有独特的免疫介导性疾病。虽然这些疾病的组成部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，但潜在的免疫学特征很差。2007年，美国进行了大约9,500例异基因血细胞移植，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%的异基因HCT受者发展为免疫介导性疾病，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的并发症是异质综合征，统称为“急性移植物抗宿主病(GVHD)”和“慢性GVHD”。慢性移植物抗宿主病是异基因红细胞移植后2年以上无复发死亡的主要原因。移植物抗宿主病的不同证候可能有不同的发病机制。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是一项综合生物学调查的观察性研究。患者将在HCT之前登记，并前瞻性地跟踪免疫介导性疾病的发展。被诊断为慢性GVHD的患者随后将通过该联盟目前资助的U01研究“改善慢性GVHD的结果评估”(PI：Stephanie Lee，CA118953-01A1,2007-2012)进行深入研究。项目2和飞行员提出了三项临床试验，目标是发病率/死亡率特别高的众所周知但知之甚少的综合征：皮肤硬化症、闭塞性细支气管炎综合征和晚期急性移植物抗宿主病。新的靶向治疗和广泛的生物分析将帮助我们更好地了解和治疗这些疾病。 儿童权利与发展中心的组成部分还侧重于培训、教育、外联以及与罕见病网络其他成员的互动。我们与三个患者倡导组织合作，向患者、家属和医生伸出援手。

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.