CYCLOPHOSPHAMIDE & CAMPATH WITH HSC IN PATIENTS WITH SCLERODERMA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。硬皮病是一种全身性疾病，被归类为免疫介导性疾病，导致皮肤和内脏器官胶原沉积。硬皮病的分子发病机制一直难以捉摸，尽管血管病变和免疫调节机制被认为是重要的。一旦发生广泛的皮肤或内脏疾病，预后明显短于普通人群。尽管已经尝试了各种治疗方法，但似乎都没有改变硬皮病的自然历史。标准剂量的免疫抑制治疗一直令人失望。近年来，环磷酰胺1~2 mg/kg/d口服或每月800~1400 mg静脉滴注，疗程6~9个月，对硬皮病肺泡炎疗效显著。最近的自体外周血干细胞移植(PBSCT)免疫消融的I期研究显示了一些有希望的数据，但确切的效果尚不确定。作为一项II期随机研究，我们建议在系统性硬皮病患者中进行自体未经操作的PBSCT和脉冲环磷酰胺治疗。

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. Scleroderma is a systemic disorder categorized as an immunologically mediated disease that causes collagen deposition of skin and visceral organs. The molecular pathogenesis of scleroderma has been elusive, although vasculopathy and immune mediated mechanisms are thought to be important. Once extensive cutaneous or visceral disease occurs, prognosis is significantly shorter than the general population. Although various treatments have been tried, none of them seems to have changed the natural history of scleroderma. Standard dose immunosuppressive treatment has been disappointing. Recently, cyclophosphamide at 1-2 mg/kg/day orally or 800-1400 mg IV monthly for 6-9 months has proven effective in treatment of scleroderma alveolitis. Recent phase I studies of immunoablation with autologous peripheral blood stem cell transplantation (PBSCT) showed some promising data, but the exact efficacy is undetermined. We propose, as a phase II randomized study, autologous unmanipulated PBSCT versus pulse cyclophosphamide in patients with systemic scleroderma.