Cord-Blood Transplants from Unrelated Donors in Patients with Hurler's Syndrome
Year: 2021
Type: article
Abstract: BACKGROUND Hurler's syndrome (the most severe form ofmucopolysaccharidosis type I) causes progressive deterioration ofthe central nervous system and death in childhood. Allogeneic bone marrow transplantation before the age oftwo 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 α-L-iduronidase activity (mean number of cells, 10.53×107per kilogram ofbody 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 ofthe 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral-blood α-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.
DOI: 10.17615/85d4-pa05
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4300546394