异基因造血干细胞移植治疗两例粘多糖累积症患儿

目的 探索造血干细胞移植治疗粘多糖累积症(mucopolysaccharidosis,MPS)的效果.方法 两例MPS患儿分别为MPS-Ⅰ H型和MPS-Ⅵ型,移植时年龄为23个月和18个月,均采用白舒菲20 ms/kg+环磷酰胺200 ms/ks进行预处理,干细胞分别来自9/10相合的无关供体和全相合同胞供体.结果 移植后11 d中性粒细胞达到0.5×109/L,14 d短串联重复序列.聚合酶链反应证实100%血细胞来自供体,移植后3个月疾病相关的酶活性分别达到70 mnol/h·mg和66 nmol/h·mg,移植后2年酶活性仍然维持在50.9nmoL/h·mg和44.5 nmol/h·mg.MPS-Ⅵ型患儿移植过程相当顺利,目前已随访28个月,健康状况良好.尽管MPS-Ⅰ H患儿移植中曾两次因肺炎合并急性心功能衰竭,但经紧急气管插管、机械通气等综合治疗后好转,随访至今也已25个月,目前心肺功能明显改善,肝脏缩小至正常大小,角膜混浊明显减轻,手指僵硬也有所改善.结论 异基因造血干细胞移植可用于治疗MPS-Ⅰ、MPS-Ⅵ;尽早移植可望减少移植相关并发症;移植所产生的临床效果需要更长时间的随访.

Treatment of 2 children with mucopolysaccharidosis by allogeneic hematopoietic stem cell transplantation

Objective Mucopolysaccharidosis(MPS) is a congenital hereditary disease.Ordy a few patients with this disease can be controlled by enzyme replacement therapy.Most of them are short of effective interference.To exploit the effect of treatment with allogenic hematopoietic stem cell transplantation,two children were treated with the transplantation.Methods The two patients included a 23 month MPS-Ⅰ H and an 18 month old MPS-Ⅵ at the time of transplantation.Busulfan of 20 mg/kg plus 200 mg of Cyclophosphamide were used as the conditioning regimen.Peripheral stem cells were collected from a 9/10 high resolution matched unrelated donor and a matched sibling carrier donor,respectively.The heart and lung were affected in the patient with MPS-Ⅰ H.Medium obstructed pulmonary impairment was found by pulmonary function test at the time of transplantation.Medium mitral valve countercurrent and patent ductus arteriosis (PDA) were found by Doppla examination.Results The number of hematopoietic stem cells was comparative between the two donors with total nucleated cells and CD34 + cells of 11×108/kg and 17 ×10S/kg,and 7.6 ×106/kg and 7.2×106/kg respectively.Neutrophil engrafted at day 11.The process of transplantation in the MPS-Ⅵ patient went smoothly with grade Ⅱ graft versus host disease(GVHD) briefly and only 1 U RBC and 2 U platelet were transfused.For the MPS-Ⅰ H patient,the process of transplantation was tough with platelet reaching to 20× 109/L till day 40 and5 U RBC and 7 U platelet were transfused during transplantation.Grade Ⅲ GVHD was resolved by steroid,mycopbenolate mofetil (MMF) and CD25 antibody.Pneumonia recurred 3 times with 2 times rescued by trachea intubation and mechanical ventilation because of accompanying acute heart failure.At day 14 the lymphocytes in both patients were 100% from donors as evidenced by short tandem repeat-PCR(STR-PCR).MPS associated enzyme activity was increased to 70 nmol/tation.Till now the 2 patients have been followed up for 25 months and 28 months with good general condition.The cardiac and pulmonary functions have improved obviously in the MPS-Ⅰ H patient.The cornea became clear in this patient.Conclusion Allogeneic hematopoietic stem cell transplantation is an effective measure W treat patient with MPS-Ⅰ H and MPS-Ⅵ.Transplantation at earlier stage of age can decrease transplant related complications.It requires longer time follow up for observing the clinical effects for these patients.