Non-myeloablative allogeneic stem cell transplantation in patients with systemic sclerosis

系统性硬化症(SSC)是一种以弥漫性硬皮病和内脏器官纤维化为特征的自身免疫性疾病。已经尝试了包括免疫抑制药物在内的各种治疗方法，但都被证明无效。为了重建免疫系统，治愈SSC患者，我们启动了非清髓性造血干细胞移植(NST)治疗SSC的临床试验。纳入标准包括年龄小于70岁，根据厚生劳动省的定义，SSC的定义，自被诊断为SSC以来持续时间不到4年，皮肤评分超过15分，以及中度器官衰竭。我们在此描述第一位参与试验的患者。一位52岁女性患有硬皮病3年，我们诊断为硬皮病。虽然她接受了泼尼松龙、环磷酰胺、青霉胺和前列腺素的治疗，但硬皮病是进行性的(皮肤评分30分)，间质肺炎…。更多的IA恶化(%VC 66.5%，血清KL-6水平1080U/mL)。2003年11月，在获得她的知情同意后，我们将她登记为第一个接受NST的患者。经小剂量全身照射(200cGy)加氟达拉滨(30 mg/m~2，3d)调理治疗后，输注由G-CSF动员的外周血干细胞。移植物抗宿主病(GVHD)的预防包括环孢素和霉酚酸酯。未进行输血。供者完全嵌合，自NST后1个月开始持续。环孢素用量逐渐减少，未见明显的急、慢性移植物抗宿主病。NST治疗3个月后，患者的皮肤评分提高到19分，皮肤活检显示轻度淋巴细胞浸润。在NST后8个月，根据CT结果，间质性肺炎面积缩小，%VC和血清KL-6水平均有显著改善(分别为70.3%和746U/mL)。NST术后1年，出现口腔粘膜慢性移植物抗宿主病和肾脏膜性肾病。虽然NST后的持续时间仍然很短，但该患者的临床病程目前看来是有希望的。较少

Systemic sclerosis (SSc) is an autoimmune disease which is characteristic of diffuse scleroderma and visceral organ fibrosis. Various kinds of therapies including immunosuppressive drugs have been attempted yet all proved ineffective. In order to reconstitute the immune system and cure SSc patients, we started a clinical trial of nonmyeloablative hematopoietic stem cell transplantation (NST) for the treatment of SSc. The inclusion criteria consisted of an age younger than 70 years, SSc as defined by Ministry of Health, Labor, and Welfare, a duration of less than 4 years since the diagnosis of SSc, a skin score of more than 15 points, and moderate organ failure. We herein describe the first patient to take part in this trial. A52-year-old female suffered from scleroderma for 3years and we diagnosed to have SSc. Although she was treated with prednisolone, cyclophosphamide, penicilamine, and prostagrandin, the scleroderma was progressive (skin score 30 points) and the interstitial pneumon … More ia also worsened (%VC 66.5%, serum KL-6 level 1080U/mL). In November 2003, we enrolled her as the first patient to undergo NST after her informed consent was obtained. After conditioning therapy consisting of low dose TBI (200 cGy) and fludarabin e (30mg/m^2, 3days), G-CSF-mobilized peripheral blood stem cells from an HLA- identical brother were infused. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. No blood transfusion was performed. Complete donor chimerism was obtained and has continued since 1 month after NST. The cyclosporine dosage was tapered gradually, and no apparent acute or chronic GVHD was seen. Three months after NST, the patient's skin score improved to 19 points and a skin biopsy showed mild lymphocyte infiltration. At 8 months after NST, the area of interstitial pneumonia decreased according to the computed tomography findings and the %VC levels and serum KL-6 level were both found to have substantially improved (70.3% and 746U/mL, respectively). 1-year after NST, she developed chronic GVHD in oral mucosa and membranous nephropathy in kidneys. Although the duration after NST is still short, the clinical course for this patient is presently appears to be promising. Less