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

系统性硬化症患者的非清髓性同种异体干细胞移植

• 批准号: 16590983
• 负责人: NISHIMURA Junji
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590983/
• 关键词: systemic sclerosis; hematopoietic stem cell transplantation; alogeneic transplantation; GVHD; 全身性強皮症; 同種造血幹細胞移植; 移植片対宿主病

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

系统性硬化症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。包括免疫抑制药物在内的各种治疗方法都被尝试过，但都被证明无效。为了重建免疫系统和治愈SSc患者，我们开始了非清髓性造血干细胞移植（NST）治疗SSc的临床试验。入选标准包括年龄小于70岁，SSc由厚生劳动省定义，自诊断SSc以来持续时间小于4年，皮肤评分大于15分，中度器官衰竭。我们在此描述了第一位参加本试验的患者。摘要一位52岁女性，罹患硬皮病3年，我们诊断为硬化症。尽管她接受了泼尼松龙、环磷酰胺、青霉胺和甘草定治疗，但硬皮病仍在进行（皮肤评分30分），间质性肺炎 ...更多信息 血KL-6水平为1080 U/mL。2003年11月，我们在获得她的知情同意后，将她作为第一个接受NST的患者入组。在由低剂量TBI（200 cGy）和氟达拉滨（30 mg/m^2，3天）组成的预处理治疗后，输注来自HLA-完全相同的兄弟的G-CSF动员的外周血干细胞。移植物抗宿主病（GVHD）预防包括环孢素和霉酚酸酯。未进行输血。获得了完全供体嵌合体，并从NST后1个月开始持续。环孢素剂量逐渐减少，未见明显的急、慢性GVHD。NST后三个月，患者的皮肤评分改善至19分，皮肤活检显示轻度淋巴细胞浸润。在NST后8个月，根据计算机断层扫描结果，间质性肺炎的面积减小，并且发现%VC水平和血清KL-6水平均显著改善（分别为70.3%和746 U/mL）。1-NST后一年，她在口腔粘膜中发展为慢性GVHD，在肾脏中发展为膜性肾病。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。少

项目成果

Fludarabine-based conditioning used in successful bone marrow transplantation from an unrelated donor in a heavily transfused patient with severe aplastic anemia.

基于氟达拉滨的调理用于成功对患有严重再生障碍性贫血的大量输血患者进行来自无关捐赠者的骨髓移植。

• 发表时间: 2005
• 期刊: Int J Hematol 81(1)
• 作者: Abe Y;Matsushima T;Tachikawa Y;Nagasawa E;Nishimura J;Nawata H;Muta K
• 通讯作者: Muta K

Successful treatment with nonmyeloablative allogeneic hematopoietic stem cell transplantation in a patient with acute myeloid leukemia complicated with pulmonary infection

非清髓性异基因造血干细胞移植成功治疗急性髓系白血病并发肺部感染患者

• 发表时间: 2004
• 期刊: International Journal of Hematology 78(1)
• 作者: Choi I;Abe Y;Otsuka R;Matsushima T;Y Tachikawa;Nagasawa E;Nishimura J;Inaba S;Nawata H;Muta K
• 通讯作者: Muta K

Steroid Myopathy : Evaluation of fiber atropy with T2 relaxation time-rabbit and human study.

类固醇肌病：用 T2 弛豫时间评估纤维萎缩-兔和人体研究。

• 发表时间: 2006
• 期刊: Radiology 238(2)
• 作者: Hatakenaka M;Soeda H;Okafuji T;Yabuuchi H;Shiokawa S;Nishimura J;Honda H
• 通讯作者: Honda H

Pivotal role of peroxisome proliferators-activated receptor γ(PPARγ) in regulation of erythroid progenitor cell proliferatio and differentiation.

过氧化物酶体增殖物激活受体γ（PPARγ）在调节红系祖细胞增殖和分化中的关键作用。

• 发表时间: 2005
• 期刊: Exp Hematol 33
• 作者: Nagasawa E;Abe Y;Nishimura J;Yanase T;Nawata H;Muta K
• 通讯作者: Muta K

Molecular remission by nonmyeloablative stem cell transplantatio after autologous peripheral blood stem cell transplantation in a patient with multiple myeloma.

多发性骨髓瘤患者自体外周血干细胞移植后通过非清髓性干细胞移植实现分子缓解。

• 发表时间: 2005
• 期刊: Leuk. Lymphoma 46(8)
• 作者: Nakashima Y;Shiratsuchi M;Tani K;Abe Y;Muta K;Shiokawa S;Nishimura J
• 通讯作者: Nishimura J