Cord-blood transplants from unrelated donors in patients with Hurler's syndrome.
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 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.


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.
Staba
Susan L
SL
Pediatric Stem Cell Transplant Program, Duke University Medical Center, Durham, NC 27710, USA. staba001@mc.duke.edu
Escolar
Maria L
ML
Poe
Michele
M
Kim
Young
Y
Martin
Paul L
PL
Szabolcs
Paul
P
Allison-Thacker
June
J
Wood
Susan
S
Wenger
David A
DA
Rubinstein
Pablo
P
Hopwood
John J
JJ
Krivit
William
W
Kurtzberg
Joanne
J
D001782:Blood Donors; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D018572:Disease-Free Survival; D005260:Female; D005312:Fetal Blood / Q000637:transplantation*; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D006128:Growth; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007068:Iduronidase / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008059:Mucopolysaccharidosis I / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D009504:Neutrophils; D019172:Transplantation Conditioning
D007166:Immunosuppressive Agents; D007068:Iduronidase; D008775:Methylprednisolone