• Susan L Staba, Maria L Escolar, Michele Poe, Young Kim, Paul L Martin, Paul Szabolcs, June Allison-Thacker, Susan Wood, David A Wenger, Pablo Rubinstein, John J Hopwood, William Krivit, and Joanne Kurtzberg.
• Pediatric Stem Cell Transplant Program, Duke University Medical Center, Durham, NC 27710, USA. staba001@mc.duke.edu
• N. Engl. J. Med. 2004 May 6; 350 (19): 1960-9.

BackgroundHurler'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.MethodsBetween 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.ResultsCord-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.ConclusionsCord 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.Copyright 2004 Massachusetts Medical Society

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