Cord-Blood Transplants from Unrelated Donors in Patients with Hurler's Syndrome

Duke University, Durham, North Carolina, United States
New England Journal of Medicine (Impact Factor: 55.87). 06/2004; 350(19):1960-9. DOI: 10.1056/NEJMoa032613
Source: PubMed


Hurler's syndrome (the most severe form of mucopolysaccharidosis type I) causes progressive deterioration of the central nervous system and death in childhood. Allogeneic bone marrow transplantation before the age of two years halts disease progression and prolongs life, but many children lack a bone marrow donor. We investigated the feasibility of using cord-blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler's syndrome.
Between December 1995 and October 2002, 20 consecutive children with Hurler's syndrome received busulfan, cyclophosphamide, and antithymocyte globulin before receiving cord-blood transplants from unrelated donors. The children were subsequently evaluated for engraftment, adverse effects, and effects on disease symptoms.
Cord-blood donors had normal alpha-L-iduronidase activity (mean number of cells, 10.53x10(7) per kilogram of body weight) and were discordant for up to three of six HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Five patients had grade II or grade III acute graft-versus-host disease; none had extensive chronic graft-versus-host disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral-blood alpha-L-iduronidase activity (event-free survival rate, 85 percent). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome.
Cord blood from unrelated donors appears to be an excellent source of stem cells for transplantation in patients with Hurler's syndrome. Sustained engraftment can be achieved without total-body irradiation. Cord-blood transplantation favorably altered the natural history of Hurler's syndrome and thus may be important to consider in young children with this form of the disease.

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    • "T-cell depletion and reduced-intensity conditioning were identified as risk factors for graft failure, whereas patients receiving cord blood had a greater likelihood of achieving sustained engraftment associated with normal enzyme levels. In 2004, unrelated UCBT was reported in 20 patients with Hurler syndrome [18] with an overall EFS rate of 85% and a probability of moderate to severe acute GVHD of 25%; all surviving patients demonstrated complete engraftment and immune reconstitution and normal peripheral-blood α-L-iduronidase activity. Two large studies comprising 93 and 45 patients with MPS1-H [6] [19], respectively, confirmed these results. "
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    • "Mucopolysaccharidosis (MPS) are a family of inherited disorders caused by deficiency of lysosomal enzymes needed to degrade glycosaminoglycans (GAGs). Since the first transplantations performed 30 years ago [107], major beneficial results have been obtained in patients with Hurler syndrome [79, 147, 150]. From these impressive results, it was expected that all MPS could be treated by HCT. "
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    • "As HSCT is increasingly successful due to improved conditioning regimens and different stem cell sources, over 80% of patients now remain alive and engrafted with a significantly improved life expectancy [24,25]. However, there is a paucity of data regarding which successfully transplanted patients will develop hip dysplasia, which patients will develop symptoms of hip dysplasia, such as pain and impaired locomotion, and when surgical intervention is needed in patients with hip dysplasia. "
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