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Previous Volume 350:1960-1969 May 6, 2004 Number 19 Next

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ABSTRACT

Background 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.

Methods 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.

Results Cord-blood donors had normal -L-iduronidase activity (mean number of cells, 10.53x10⁷ 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 -L-iduronidase activity (event-free survival rate, 85 percent). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome.

Conclusions 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.

Source Information

From the Pediatric Stem Cell Transplant Program, Duke University Medical Center, Durham, N.C. (S.L.S., P.L.M., P.S., J.A.-T., S.W., J.K.); the Center for Development and Learning (M.L.E.) and the Frank Porter Graham Child Development Center (M.P.), University of North Carolina School of Medicine, Chapel Hill; Emmes Corporation, Rockville, Md. (Y.K.); Jefferson Medical College, Philadelphia (D.A.W.); the Placental Blood Program, New York Blood Center, New York (P.R.); Women's and Children's Hospital, Adelaide, Australia (J.J.H.); and the University of Minnesota School of Medicine, Minneapolis (W.K.).

Address reprint requests to Dr. Staba at Box 3350, Duke University Medical Center, Durham, NC 27710, or at staba001{at}mc.duke.edu.

Full Text of this Article

Related Letters:

Cord-Blood Transplants from Unrelated Donors in Hurler's Syndrome
Fujisaki G., Kami M., Kishi Y., Staba S. L., Kurtzberg J.
Extract | Full Text | PDF  
N Engl J Med 2004; 351:506-507, Jul 29, 2004. Correspondence

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