成人脂肪源间充质干细胞治疗顽固急性移植物抗宿主病(英文)

Human adipose-derived stem cells for treatment of severe refractory acute graft-versus-host disease

背景:目前为止,医学界仍然没有一种有效的策略治疗对糖皮质激素耐药的、严重的急性移植物抗宿主病;很多药物包括抗胸腺细胞球蛋白、霉酚酸酯、喷司他丁及单克隆抗体等均已经临床尝试,但疗效均不尽人意。目的:进一步评价成人脂肪源间充质干细胞作为挽救方案用于治疗对糖皮质激素耐药的急性移植物抗宿主病。设计:临床实验。单位:河南省肿瘤医院,河南省血液病研究所血液科。对象:实验于2002-09/2005-08在河南省血液病研究所完成,经河南省肿瘤医院医学伦理委员会批准。共有8例出现Ⅲ～Ⅳ度对糖皮质激素耐药的急性移植物抗宿主病的患者入选本实验,患者及脂肪源间充质干细胞供者对治疗及实验均知情同意。方法:8例对糖皮质激素耐药的Ⅲ～Ⅳ度急性移植物抗宿主病患者患者均经静脉输入成人脂肪源干细胞(剂量为1.0×106/kg),其中1例患者接受两次成人脂肪源干细胞输注,其余7例患者均接受一次成人脂肪源干细胞治疗。在这8例患者中,4例患者接受的成人脂肪源干细胞来源于HLA配型完全相合的家庭供者,其余4例患者接受的成人脂肪源间充质干细胞来源于无血缘关系的无关供者。主要观察指标:成人脂肪源间充质干细胞用于治疗对糖皮质激素耐药的急性移植物抗宿主病的疗效。结果:所有接受成人脂肪源间充质干细胞治疗的8例患者均无明显副作用出现;在接受成人脂肪源干细胞治疗的8例患者中,除1例患者(后死于多器官功能衰竭)对治疗无反应外,另7例患者的病情(对糖皮质激素耐药的急性移植物抗宿主病)很快得以缓解;在对成人脂肪源干细胞治疗反应良好的7例患者中,有6例患者存活11～90个月,中位时间30个月,其中4例患者目前仍处于血液学完全缓解状态且生存状况良好,另1人在接受成人脂肪源干细胞治疗后13月后死于白血病复发。结论:成人脂肪源间充质干细胞非常有希望用于治疗对糖皮质激素耐药的急性移植物抗宿主病。

BACKGROUND： There is no consistently effective therapy for patients with steroid-refractory acute graft-versus-host disease （GVHD）. A variety of alternative approaches have been tested, including antithymocyte globulin, mycopbenolate mofetil （MMF）, pentostatin, and monoclonal antibodies; however, these treatments have been only modestly successful. OBJECTIVE： To further evaluate the efficacy of human adipose-derived stem cells （ASCs） as the salvage therapy for steroid-refractory acute GVHD. DESIGN： A clinical trial. SETTING： Department of Haematology, Henan Institute of Haematology, Henan Tumor Hospital. PARTICIPANTS： The clinical trial was performed at the Henan Institute of Haematology from September 2002 to August 2005. Eight patients were treated with ASCs for grades Ⅲ-Ⅳ steroid-resistant acute GVHD. The study was approved by the Ethics Committee at Henan Tumor Hospital and informed consent was obtained from patients and ASCs donors before they enrolled. METHODS： Eight patients with steroid-refractory grades Ill-IV acute GVHD received intravenous infusions of ASCs. The ASCs dose was 1.0× 10^6/kg. Seven patients were treated once and one patients twice. Four patients received ASCs from haplo-identical family donors and four from unrelated mismatched donors. MAIN OUTCOME MEASURES： The efficacy of human ASCs as the salvage therapy for steroid-refractory acute GVHD. RESULTS： No side effects were noted after the ASCs infusions. Acute GVHD disappeared completely in seven of eight patients and six of these seven patients are still alive after the median follow-up of 30 months （range 11-90 months） after the initiation of ASCs therapy. All four surviving patients were in good clinical condition and in remission of their hematological malignancy. Two patients died-one with no obvious response to ASCs died of multiorgan failure and one of relapse of leukemia. CONCLUSION： These results suggest that ASCs is a very promising treatment for severe steroid-resistant acute GVHD.