CYCLOPHOSPHAMIDE AND CAMPATH IN PATIENTS WITH SLE: PHASE I CLINICAL TRIAL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。系统性红斑狼疮（SLE）是一种多系统炎性疾病，其特征是产生抗体，与许多不同的自身抗原反应。尽管在表现、表现和临床病程上存在差异，但系统性红斑狼疮患者的共同因素是T细胞和B细胞对内源性刺激的高反应性。目前，在发达国家，SLE的死亡率估计为每百万人年3人。许多因素与预后不良有关；这些包括肾脏疾病的存在导致血清肌酐或尿蛋白排泄高于正常水平，高血压，肾活检显示弥漫性增生性肾小球肾炎，活检显示慢性改变，肺部受累，首次红斑狼疮门诊就诊时系统性红斑狼疮疾病活动指数（SLEDAI）评分较高，贫血，血小板减少症和磷脂抗体。该试验旨在评估高剂量环磷酰胺和campaign - 1h免疫消融治疗系统性红斑狼疮患者的安全性和有效性，随后使用外周干细胞进行救援。本研究的主要结局是SLE缓解两年，这是根据受试者在每个类别中的基线不列颠群岛狼疮评估组（BILAG）评分来定义的。缓解被定义为在所有最初为A或B的类别中BILAG评分为C或D，在所有最初为C的类别中BILAG评分为D，在所有最初为D或E的类别中BILAG评分为D或E。BILAG评分将在移植后6个月和12个月进行评估，然后在研究期间每年进行评估

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Systemic lupus erythematosus (SLE) is a multi-system, inflammatory disorder characterized by the production of antibodies that react with many different self-antigens. Despite differences in presentation, manifestations, and clinical course, the common factor for patients with systemic lupus erythematosus is hyper-reactivity of T and B cells to endogenous stimuli. Currently, in developed countries, mortality from SLE is estimated at three per million person-years. A number of factors are associated with poor prognosis; these include the presence of renal disease causing an elevation in serum creatinine or urine protein excretion above normal, hypertension, diffuse proliferative glomerulonephritis on renal biopsy, chronic changes on biopsy, lung involvement, a high Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at the time of first lupus clinic visit, anemia, thrombocytopenia, and antibodies to phospholipids. This trial is designed to evaluate the safety and efficacy of treating systemic lupus erythematosus participants with high dose cyclophosphamide and CAMPATH-1H immune ablation, followed by rescue with peripheral stem cells. The primary outcome for this study is SLE remission at two years, which is defined according to the subject¿s baseline British Isles Lupus Assessment Group (BILAG) score within each category. Remission is defined as BILAG score of C or D in all categories that were initially A or B, BILAG score of D in all categories that were initially C, and a BILAG score of D or E in all categories that were initially D or E. The BILAG score will be evaluated six and 12 months post transplant, and then yearly for the duration of the study