Clinical Study of Allogenetic Hematopoietic Stem Cell Transplantation for Three Cases of Leukodystrophy

Allogenetic hematopoietic stem cell transplantation (Allo-HSCT) can be used to cure some genetic leukodystrophy patients in current. This clinical study is to investigate efficacy and practicability of Allo-HSCT in treatment of genetic leukodystrophy in China.

Three boy diagnosed genetic leukodystrophy (2 cases of metachromatic leukodystrophy, 1 case of X□|linked adrenoleukodystrophy) had undergone allogeneic Stem cell Transplantation. A 32 month old boy accepted HLA 8/10 high-resolution matched unrelated umbilical cord blood as graft, which contained nucleated cells 13.5×10⁷/kg. A 2 year-old boy accepted HLA high-resolution 10/10 matched unrelated peripheral blood stem cells (PBSC) as graft which contained mononuclear cells 8 ×10⁸/kg. The conditioning regimen consisted of cyclophosphamide (60–100 mg/kg), fludarabine (150–200mg/kg), TT (5mg/kg) and busulfan (12–13.2 mg/kg). A 12 year-old boy accepted sibling HLA low resolution 6/6 (A, B, DRB1) matched bone marrow as graft which contained mononuclear cells 1.23 ×10⁸/kg. The conditioning regimen consisted of busulfan (16mg/kg) and cyclophosphamide (200mg/kg). Cyclosporine A and mycophenolate mofetil were used to prevent graft versus host disease (GVHD). ATG-Fresenius (15 mg/kg) and low dose of methotrexate were added for prophylaxis of GVHD in unrelated PBSC transplantation. XY chromosome by the FISH method or quantitative PCR for short tandem repeat (STR) were used to identify the chimerism. ASA level in peripheral blood leukocytes and C26:0 plasma level were monitored after transplantation respectively.

1. Complete chimerism and hematopoietic reconstitution were successfully achieved in 3 patients, the ANC engrafted from +10 to +17 days, the time of platelets>20×109/L was from +11 to +35 days.

2. Arylsufatase A level in peripheral blood leukocytes was significantly increased to the normal range in 2 cases of metachromatic leukodystrophy on day +28 and were stable in monthly detection for 4–5 months. C26:0 plasma level began to decrease on the 2nd months after transplantation, and reached to normal range on the 8^thmonth after transplantion in the case of X□|linked adrenoleukodystrophy.

3. The 3 patients have survived for 4,5 and 50 months respectively up to now. One patient with severe CNS symptoms before transplantation got recurrent lung infection after transplantation related to the swallowing difficulty. Another 2 patients have no progressive disease.

4. Three patients have not got any acute graft-versus-host-disease.

Allogenetic hematopoetic stem cell transplantation is effective and feasible in the treatment of some childhood genetic leukodystrophy patients. These patients should accept allo-HSCT in the early stage of disease in order to get good survival.

No relevant conflicts of interest to declare.