Chen Jing, Jiang Hua, Dong Lu, Wang Yaoping, Luo Changying, Zhou Min, Zhang Weiming, Huang Shangzhi, Gu Xuefan, Qiu Wenjuan, Zhang Huiwen, Gu Longjun
Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Dec;25(6):675-7.
Mucopolysaccharidosis(MPS) is a congenital hereditary disease. Only 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.
The two patients included a 23 month MPS-IH 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-IH. 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.
The number of hematopoietic stem cells was comparative between the two donors with total nucleated cells and CD34+ cells of 11 x 10(8)/kg and 17 x 10(8)/kg, and 7.6 x 10(6)/kg and 7.2x 10(6)/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-IH patient, the process of transplantation was tough with platelet reaching to 20 x 10(9)/L till day 40 and 5 U RBC and 7 U platelet were transfused during transplantation. Grade III GVHD was resolved by steroid, mycophenolate 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/h.mg and 66 nmol/h.mg at 3 month and still remained 50.9 nmol/h.mg and 44.5 nmol/h.mg at 2 years post transplantation. 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-IH patient. The cornea became clear in this patient.
Allogeneic hematopoietic stem cell transplantation is an effective measure to treat patient with MPS-IH 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.
黏多糖贮积症（MPS）是一种先天性遗传性疾病。该疾病仅有少数患者可通过酶替代疗法得到控制，大多数患者缺乏有效的干预措施。为探究同种异体造血干细胞移植的治疗效果，对两名患儿进行了该移植治疗。
两名患者在移植时，一名为23个月大的MPS - IH患儿，另一名为18个月大的MPS - VI患儿。采用20mg/kg白消安加200mg环磷酰胺作为预处理方案。分别从一名9/10高分辨率匹配的无关供体和一名匹配的同胞携带者供体采集外周干细胞。MPS - IH患者的心脏和肺部受到影响，移植时通过肺功能测试发现中度阻塞性肺损伤。通过多普勒检查发现中度二尖瓣反流和动脉导管未闭（PDA）。
两名供体的造血干细胞数量具有可比性，总有核细胞分别为11×10⁸/kg和17×10⁸/kg，CD34⁺细胞分别为7.6×10⁶/kg和7.2×10⁶/kg。中性粒细胞在第11天植入。MPS - VI患者的移植过程顺利，短暂出现II级移植物抗宿主病（GVHD），仅输注了1单位红细胞和2单位血小板。对于MPS - IH患者，移植过程艰难，血小板在第40天达到20×10⁹/L，移植期间输注了5单位红细胞和7单位血小板。III级GVHD通过类固醇、霉酚酸酯（MMF）和CD25抗体得到缓解。因伴有急性心力衰竭，肺炎复发3次，2次通过气管插管和机械通气抢救。在第14天，通过短串联重复序列PCR（STR - PCR）证明两名患者的淋巴细胞100%来自供体。移植后3个月时，MPS相关酶活性分别提高到70nmol/h.mg和66nmol/h.mg，移植后2年仍分别为50.9nmol/h.mg和44.5nmol/h.mg。目前，两名患者已分别随访25个月和28个月，总体状况良好。MPS - IH患者的心肺功能明显改善。该患者的角膜变得清晰。
同种异体造血干细胞移植是治疗MPS - IH和MPS - VI患者的有效措施。在年龄较小阶段进行移植可减少移植相关并发症。对这些患者需要更长时间的随访以观察临床效果。
