摘要
目的 探讨脐带血干细胞移植对假肥大型肌营养不良症(DMD)治疗的可行性。方法对1例确诊为有家族史的11岁DMD患儿经HLA配型,在脐血库中寻找到1份有5个位点相合的干细胞,其细胞数为移植治疗用量的2 6倍。采用白消安、环磷酰胺和兔抗胸腺淋巴细胞球蛋白预处理后进行异基因脐带血干细胞移植治疗;术后给予环孢素A、泼尼松龙和骁悉预防移植物抗宿主反应,前列腺素E1预防肝静脉阻塞综合征,丽科伟预防巨细胞病毒感染,粒细胞刺激因子惠尔血和丙种球蛋白进行对症支持治疗,定期检测血清肌酸激酶(CK)、造血重建、血型转变和PCR STR。结果 移植后第12天外周血白细胞为0. 5×109 /L,第14天1. 0×1.09 /L,中性粒细胞数为0 .6×109 /L, 第37天停用粒细胞刺激因子,白细胞波动在3 .34×109 /L^12 .2×109 /L;第27天血小板>20×109 /L,血红蛋白于第24天上升至88g/L,停用红细胞输注。移植后第42天患儿的血型从移植前的A型转变为AB型(移植干细胞为B型);PCR -STR检测均呈混合嵌入,供者的比例逐渐上升至55% ~65%。第38天出现Ⅰ度移植物抗宿主病,CK从6000U/L降至600~2200U/L。移植后第42天的运动功能较移植前有所改善。结论 异基因脐带血干细胞移植后短期内可恢复造血重建并改善患儿的运动功能。
Objective To study the feasibility of treatment of Duchenne muscular dystrophy (DMD) with umbilical cord stem cell transplantation.Methods HLA matching was conducted for a 11-year-old DMD boy with family history was underwent umbilical cord blood stem cell transplantation and a sample of umbilical cord stem cells with 5 matched HLA sites was found in the cord blood bank with 27.32×.108 nucleated cells, about 2.6 times that of the treatment dosage for him. After pretreatment with busulfan 14 mg/kg·d, cyclophosphamide 50 mg/ kg·d, and rabbit anti-human thymocyte globulin 10 mg/ kg·d, the allogeneic cord blood stem cells were transplanted intravenously. Cyclosporin A, methylprednisolone and MMF were used after the transplantation so as to prevent graft versus host reaction. Prostaglandin E1 was used to prevent Budd-Chiari syndrome, and ganciclovir was used to prevent cytomegalovirus infection. At the same time, Gran, granulocytic cell stimulating factor, and gammaglobulin were also used. Biochemistry test, including serum creatine kinase (CK), was conducted. Evidence of reconstruction of blood making, including conversion of blood type, was observed. PCR-STR analysis was used to observe the status of implantation of the donor umbilical cord blood stem cells.Results (1)12 days after transplantation, the white blood cells (WBC) of peripheral blood were 0.5×109/L, 14 days after, the numbers of WBC and neutrophils were 1.0×109/L and 0.6×109/L respectively. In 37 days, granulocytic cell stimulating factor was no more used, the peripheral blood WBC fluctuated around 3.34~12.2×109/L. In the 27th day, the number of blood platelets was more than 20×109/L and hemoglobin rose to 88 g/L. On the 24th day red blood cells transfusion was stopped. (2)In the 42nd day, the blood type of the patient transformed from type A before transplantation to type AB ( the blood type of transplanted stem cells is type B ). (3)PCR-STR test of the peripheral blood made 17, 26, and 42 days after transplantation showed that the gene type of the patient was mixed mosaic: The ratio of donor gradually increased from 40%~45% to 55%~65%.(4)In the 38th day I°GVHD appeared.(5)serum CK level declined from 6000 U/L to 600~2200 U/L. (6)In the 42nd day, physical examination revealed obviously improvement in walking, turning the body over, and standing up.Conclusion This is first case of prospective clinical transplantation on DMD by allogeneic cord blood stem cell. Umbilical cord stem cell transplantation helps re-build blood-making function, and improve locomotive function with a mild GVHD reaction. The genotype of rebuilt blood is mosaic but the ratio of gene mosaic gradually turn from recipient gene type>donor gene type to recipient gene type<donor gene type. The serum CK level decreases significantly after transplantation, which may slow down the necrosis of muscle cell. DMD patient will be benefited by stem cell transplantation.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2005年第8期522-525,共4页
National Medical Journal of China
基金
国家自然科学基金资助项目(30170337
30370510)
卫生部临床学科重点项目 (2001321 )
博士点专项科研基金(20030558058)
