Two Cases Report of Haploid Hematopoietic Stem Cell Transplantation Treatment of Adrenal Leukodystrophy

Background: Adrenal leukodystrophy is one of the beta oxidation peroxidase disease, an x-linked recessive heredity, can lead to very long chain fatty acids in tissue accumulation, result in adrenal and cerebral white matter of the progressive deterioration. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for early childhood cerebral type of X-ALD. We report two cases of haploid hematopoietic stem cell transplantation for the treatment of adrenal leukodystrophy.

Methods: Two patients were male, 5 years old, 6 years old, respectively, by the gene diagnosis of adrenal leukodystrophy.Case 1 received father haploid bone marrow and peripheral blood stem cell(HLA7/10 match)combine with unrelated umbilical cord blood(HLA 9/10 match). Case 2 received sister haploid bone marrow and peripheral blood stem cell(HLA5/10 match)combine with unrelated umbilical cord blood(HLA 7/10 match).Case 1 conditioning regimen use cyclophosphamide, fludarabine and thiotepa.Case 2 conditioning regimen use cyclophosphamide , busulfan ,fludarabine , rabbit anti-human thymocyte immunoglobulin and thiotepa.Case 1 bone marrow infused total nucleated cell dose was 2×108/kg (CD34+:0.75%,CD3+:1.67%), peripheral blood stem cell infused total nucleated cell dose was 29×108/kg (CD34+:0.19%,CD3+:4.96%), unrelated umbilical cord blood infused total nucleated cell dose was 1.16×108/kg (CD34+:0.44%). Case 2 bone marrow infused total nucleated cell dose was 0.89×108/kg (CD34+:0.74%,CD3+:2.29%), peripheral blood stem cell infused total nucleated cell dose was 25.85×108/kg (CD34+:0.5%,CD3+:15.23%), unrelated umbilical cord blood infused total nucleated cell dose was 0.39×108/kg (CD34+:0.93 %). GVHD prophylaxis Case 1 used mycophenolate mofetil,sirolimus,while Case 2 used mycophenolate mofetil,tacrolimus and sirolimus.

Results: The absolute neutrophil count (ANC) greater than 0.5×109/L of two patients were 21 and 23 days , case 1 had a successful engraftment with father donor-derived as case 2 had a successful engraftment with umbilical cord blood donor-derived.Follow-up time of 35 months and 3 months respectively,Case 1 Check head MRI again show a smaller lesionswhile Case 2 progression-free.Two cases' C24:0, C26:0, C24:0 / C22:0, C26:0 / C22:0 of plasma decline than before transplantation.

Conclusion: In the absence of HLA-match donor, haploid bone marrow and peripheral blood stem cell combined unrelated umbilical cord transplantation is a effective method of treatment of adrenal leukodystrophy, but which will successful engraftment need more further studies.