【作者】 莫金祖；

【导师】 莫雪安；

【作者基本信息】 广西医科大学 ， 神经病学， 2012， 硕士

【摘要】 目的：观察与研究自体外周血造血干细胞移植(APBSCT)治疗重症肌无力(MG)的安全性及近,远期疗效的。方法：MG患者四例,移植前血浆置换3-4次,胸腺局部照射20-25Gy,若合并胸腺瘤者行手术切除。后联用环磷酰胺(CTX)和粒细胞集落刺激因子(G-CSF)动员自体外周血造血干细胞(APBSCs),并经血细胞分离仪分离和采集后4℃保存(72h内)。经环磷酰胺+马法兰方案预处理后,经锁骨下静脉回输APBSCs。回输后用抗淋巴细胞球蛋白(ALG)体内去除T细胞,并用G-CSF提升白细胞。当中性粒细胞>0.5×109/L、血小板>50×109/L时,提示造血功能重建,移植成功。移植后通过观察移植前后患者临床症状、体征及实验室指标的改变评价疗效。结果：例1经APBSCT后肌无力症状、体征逐渐缓解,T淋巴细胞亚群和神经电生理均有不同程度的恢复,2年后临床症状体征完全缓解消失,电生理恢复正常,停用抗胆碱酯酶药,能正常工作及生活,2005年至2007年无复发,,至08年后同前无力症状再发,靠激素和抗胆碱酯酶药维持治至今。例2行APBSCT后5个月,临床症状和体征完全缓解,神经电生理恢复正常,随访至今9年无复发。例3行移植后仅2个月,肌无力症状、体征明显好转,神经电生理明显改善,但仍有两侧软腭上提力差,闭眼无力,鼓腮无力等无力症状,3年后上述无力症状体征完全缓解,电生理恢复正常,随访至今8年无复发。例4移植后约1月开始起效,5个月后明显好转,全身肌力改善,以四肢改善明显,肌力5—级,可以适当下地劳动,无呼吸乏力,眼肌和面肌恢复稍慢。1年2个月后复查,上睑下垂四肢乏力等症状体征较移植前明显改善,但出现四肢腱反射亢进,以双下肢明显,呈(++++),双踝阵挛亦较前明显,呈持续性,并出现双侧病理征明显阳性,远期疗效仍有待进一步观察。结论：APBSCT治疗MG安全、有效,远期疗效肯定,但不排除存在复发风险；MG患者APBSCT前神经低频重复电刺激检查可在一定程度上预测移植后肌力的恢复情况；.出现越早,越重的症状恢复越慢,出现越迟,越轻的恢复越快；临床症状恢复较实验指标恢复快；临床恢复与抗乙酰胆碱受体抗体指标呈不一致性。更多还原

【Abstract】 To explore the clinical effect and safty of treatment of Refractory Myasthenia Gravis by autologous peripheral blood stem cell transplantationin, four MG patients were chosen to deal with the method.Methods:autologous peripheral blood stem cells (APBSCs) were mobilized with cyclophosphamide (CTX) and granulocytecolony-stimulating factor (G-CSF).The CD34+cells harvesting was performed by continuous flow leukapheresis using a CS-3000plus blood separator, then APBSCs were collected and preserved at4℃in refrigerator.then the patients were conditioned by CTX (60mg/kg/d, for2days)+maphalan(120mg/m2/d, for1day)+thymus radiotherapy+plasma exchange. To clear away T cell, antilymphocyteglobulin was used (10mg/kg/d, for2days)after APBSCs had been reinfused.Granulocyte recovery was stimulated by G-CSF. The four patients’ clinical manifestations and immunologic markers were compared before and after transplantation.Results:1,The first MG patients got an excellent clinical remission after transplantation in2～8months,and The patients’ clinical manifestations and immunologic markers were completely remission after about two years. But she took the disease again two years latter. Then she had to take back hormone and anticholinesterase drugs to keep her physical strength.2.the second MG patient were completely remission after five months. there was no relapse by nine years observed results.3.The third patient got an excellent clinical remission after transplantation in about2months, too. Then completely remission afte about3years. There was no relapse by8years observed results.4.The forth MG patient felt batter after the transplantation in about5months,and he can do some housework as normal.lyear and2months latter, he got an excellent clinical remission,too. Conclussions:APBSCT is effective and safe for MG, and the long-term effect is sure. But there may be some risk of relapse. The repetitive nerve stimulation test before transplantation is helpful in predicting the recovery of MG after APBSCT to some extent.The earlier and heavier the symptom is, the later it would disappear. The clinical symptoms recover faster than The index. The Clinical recovery donot stay the same with the high-low lines Of AchRab index.更多还原