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目的粘多糖病I型是一种进行性多器官受累的遗传代谢性疾病,Hurler综合征是粘多糖病I型的最严重类型,常导致进行性的中枢神经系统受损和早期死亡。该研究进行了异基因造血干细胞移植治疗该病的初步尝试,探讨异基因干细胞移植治疗粘多糖病的疗效。方法1例男性粘多糖病I型Hurler综合征患者,2岁1个月,供者为其胞姐,HLA配型一个HLA-B位点不合。预处理方案为减低预处理剂量的BuCy方案马利兰(BU)每日3.7mg/kg,-9~-6d;环磷酰胺(Cy)每日42.8mg/kg,-5~-2d;抗胸腺细胞球蛋白每日3.5mg/kg,-7,-5,-3,-1d。输入重组人粒细胞集落刺激因子动员的供者CD34+细胞(12.8×106/kg),以环孢素A、骁悉、赛呢哌、抗胸腺细胞球蛋白和氨甲喋呤预防移植物抗宿主病(GVHD)。结果移植后14d,短串联重复序列结合聚合酶链反应(STR-PCR)检测显示为完全供者型嵌合,中性粒细胞和血小板植活时间分别为+11d和+19d。仅出现肝、胃肠Ⅰ级预处理相关毒性,无严重预处理相关并发症。未发生急、慢性移植物抗宿主病和移植物衰竭,移植后临床症状明显改善,认知能力持续增加。结论异基因造血干细胞移植治疗粘多糖病I型疗效肯定,减低剂量的预处理方案有利于降低预处理相关毒性;移植前后加强免疫抑制治疗,适当增加供者造血干细胞输注数量,有利于促进植入,减少移植物衰竭以及GVHD的发生。
Purpose Mucopolysaccharidosis Type I is a progressive, multiorgan-involved genetic metabolic disorder that is the most severe type of mucopolysaccharidosis type I and often leads to progressive central nervous system compromise and early death. The study conducted allogeneic hematopoietic stem cell transplantation in the treatment of the disease attempt to explore the efficacy of allogeneic stem cell transplantation for the treatment of mucopolysaccharidosis. Methods One male patient with type 1 Hurler syndrome of mucopolysaccharidosis was 2 years old and 1 month old. The donor was his sister cell and HLA-B allele was HLA-B. The pretreatment regimen consisted of BuCy regimen (3.7 mg / kg, -9 ~ 6 d daily), and 42.8 mg / kg cyclophosphamide (Cy) daily for -5 ~ Globulin daily 3.5mg / kg, -7, -5, -3, -1d. The donor CD34 + cells (12.8 × 106 / kg) mobilized by recombinant human granulocyte colony stimulating factor (CSF) were administered to patients with GVHD (cyclosporin A, nifedipine, citalopril, antithymocyte globulin and methotrexate) ). Results 14 days after transplantation, the short tandem repeat and polymerase chain reaction (STR-PCR) showed complete donor chimerism. The neutrophil and platelet engraftment time was +11 d and +19 d, respectively. Only liver, gastrointestinal grade Ⅰ pretreatment related toxicity, no serious pre-treatment related complications. No acute and chronic graft-versus-host disease and graft failure occurred. The clinical symptoms were significantly improved and the cognitive ability continued to increase after transplantation. Conclusion Allogeneic hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis type I effect is positive, reduce the dose of pretreatment program is conducive to reduce the pretreatment-related toxicity; before and after transplantation to strengthen immunosuppressive therapy, appropriate increase in donor hematopoietic stem cell infusion is conducive to the promotion of Into, reduce graft failure and GVHD.