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

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.