异基因造血干细胞移植治疗2例黏多糖贮积症Ⅱ型患儿临床分析

The clinical analysis of allogeneic hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis type Ⅱ

目的探讨造血干细胞移植治疗黏多糖贮积症Ⅱ型的疗效及后置环磷酰胺在本病中的应用。方法选取本院2例确诊为黏多糖贮积症Ⅱ型的患儿,2例均为男性,移植时年龄分别为3岁8月和2岁11月,预处理方案采用减低强度的白消安(busulfex,Bu)+氟达拉滨(fludarabine,Flu)方案:Bu 1mg/(kg·次),每6小时1次,提前2~5天;Flu 40mg/m2,提前3~6天,抗胸腺球蛋白总量7.5mg/kg,分4天静脉滴注,提前2~5天。预防移植物抗宿主病(graft-versus-host disease,GVHD)方案:移植后3~4天予以40mg/kg环磷酰胺静脉滴注,予以短疗程甲氨蝶呤静脉滴注,移植后5天起予以环孢霉素A静脉滴注、口服吗替麦考酚酯。干细胞均来自半相合的父亲。结果 2例患者分别于移植后12~14天中性粒细胞达到0.5×109/L,移植后10~14天血小板植活,移植后14天短串联重复序列结合聚合酶链反应(short tandem repeat-polymerase chain reaction,STR-PCR)检测显示为完全供者型嵌合。移植过程中无明显化疗相关不良反应,无严重预处理相关并发症,未发生GVHD。移植后1个月复查酶活性均达正常值,移植后患儿指端关节活动较前灵活,肝脾较前明显回缩,认知能力进步。结论异基因造血干细胞移植治疗黏多糖贮积症Ⅱ型效果确切,减低强度预处理方案减少移植相关并发症,后置环磷酰胺可用于本病,并有效减少移植物抗宿主病。

Objective To exploit the effect of treatment with allogenic hematopoietic stem cell transplantation and administration of high doses of cyclophosphamide early after haplo BMT in these cases. Method 2 cases children which diagnosed as mucopolysaccharidosis type Ⅱ in our hospital were selected. A 44-month-old boy and a 35-month-old boy were included at the time of transplantation. The reduced-intensity of Bu＋Flu conditioning regimen in allo-HSCT for this patient was as follows： busulfan 4mg/kg at 2 to 5 days before transplantion, fludarabine 40mg/m2 at 3 to 6 days before transplantion,rabbit antithymocyte globulin 2.5mg/kg daily at 3 to 5 days before transplantation. Graft-versus-host disease（GVHD） prophylaxis： short-course methotrexate, and post transplantation high-dose cyclophosphamide on days 3 and 4 was followed by mycophenolate mofetil and cyclosporine. The donors were their HLA-haploidentical father. Result Neutrophil engraftment occurred on days 12 and 14 after transplantation respectively, platelet engraftment occurred on day 10 and 14 after transplantation respectively. Complete donor type engraftment was confirmed by Short Tandem Repeat-Polymerase Chain Reaction（STR-PCR） on day 14 after transplantation. No regimen-related toxicity occurred, GVHD and graft failure were not observed.1 month after transplantation, the activity of the iduronate-2-sulfatase was increased to normal.The motion of metacarpophalangeal joints ameliorated, regression of hepatosplenomegaly, the neurocognitive function improved. Conclusion Allogeneic hematopoietic stem cell transplantation is an effective measure to treat patient with MPS-Ⅱ.The reduced-intensity conditioning regimen was helpful to decrease the regimen-related toxicity. Posttransplant cyclophosphamide approach successfully used and reduced the incidence of GVHD.