May 5, 2004 -- Cord blood from unrelated donors is an excellent source for stem cell transplant to treat children with Hurler's syndrome, according to the results of a study published in the May 6 issue of the New England Journal of Medicine.

"Hurler's syndrome (the most severe form of mucopolysaccharidosis type I) causes progressive deterioration of the central nervous system and death in childhood," write Susan L. Staba, MD, from Duke University Medical Center in Durham, North Carolina, and colleagues. "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 were treated with busulfan, cyclophosphamide, and antithymocyte globulin, but they did not undergo total-body irradiation. They then received cord-blood transplantation from unrelated donors with normal α-L-iduronidase activity (mean number of cells, 10.53 × 10 ⁷ per kilogram of body weight) and discordance for up to three of six HLA markers. Median age at cord-blood transplantation was 16 months.

Neutrophil engraftment occurred a median of 24 days after transplantation. Although five children had grade II or grade III acute graft-versus-host disease (GVHD), none had extensive chronic GVHD.

At a median of 905 days after transplantation, 17 of the 20 children were alive and had complete donor chimerism and normal peripheral-blood α-L-iduronidase activity. Event-free survival rate was 85%. These children also had improved neurocognitive performance and decreased somatic features of Hurler's syndrome.

"Although long-term follow-up is needed to determine the full effect of cord-blood transplantation on the natural history of Hurler's syndrome, patients appear to derive important benefits from this therapy," the authors write. "It may prove to be a therapeutic option for young patients with Hurler's syndrome who lack an HLA-matched, related bone marrow donor who is not a carrier of the disease."

The authors recommend additional studies to determine whether the positive outcomes in this study were related to the stem-cell source, the age at transplantation, or both.

The National Heart, Lung, and Blood Institute of the National Institutes of Health helped support this study.

In an accompanying perspective, Joseph Muenzer, MD, PhD, and Amy Fisher, MS, from the University of North Carolina at Chapel Hill, summarize the evolving history of management in Hurler's disease. Hematopoietic stem-cell transplantation is now the treatment of choice for a child younger than two years of age with minimal or no central nervous system disease, while enzyme-replacement therapy with recombinant α-L-iduronidase (laronidase) is recommended for children with the milder or attenuated forms of mucopolysaccharidosis type I and for patients with neurologic impairment.

"When mucopolysaccharidosis is diagnosed in a patient, the family and primary care providers will immediately encounter an unfamiliar realm of medical knowledge regarding the implications of the diagnosis, as well as the treatment options of hematopoietic stem-cell transplantation and enzyme-replacement therapy," the editorialists write. "Adequate counseling on these options, including the risks and benefits associated with each, is crucial for those embarking on this difficult, possibly time-sensitive decision-making process, which is made more challenging by the emotionally charged experience of receiving the diagnosis."

Dr. Muenzer reports having received consulting fees and research support from Transkaryotic Therapies, lecture fees from Genzyme, and consulting fees from Biomarin Pharmaceuticals.

N Engl J Med. 2004;350:1932-1934, 1960-1969