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Cord blood transplant may be effective in Hurler’s syndrome
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Umbilical cord blood stem cell transplantation was associated with favorable survival and full donor chimerism rates in a cohort of children with Hurler’s syndrome, according to study results.
The report includes data for transplantation results among 258 children with a median age of 16.7 months. Median follow-up was 57 months. Eligible participants underwent a myeloablative conditioning regimen between 1995 and 2007.
Jaap Jan Boelens
At day 60, the cumulative incidence of neutrophil recovery was 91%. At day 100, grade 2 to 4 graft-versus-host disease (GVHD) had occurred in 25% of patients. The 5-year chronic GVHD rate was 16%.
Researchers reported a 5-year OS rate of 74% and a 5-year EFS rate of 63%.
Among children who received HLA-matched sibling donor cells or 6/6 matched unrelated cord blood, the EFS rate was 81%. The EFS rate was 66% among children who received 10/10 HLA-matched unrelated donations and 68% among those who received 5/6 matched cord blood.
EFS rates were lower still among children who received 4/6 matched unrelated cord blood (57%; P=.031) and HLA-mismatched unrelated donations (41%; P=.007).
Cord blood transplantation was linked to a 92% full donor chimerism rate, compared with a 69% chimerism rate among matched sibling donation, unrelated donation and T-cell–depleted unrelated donations (P=.039). Cord blood transplantation also was associated with higher normal enzyme levels than the other graft sources (98% vs. 59%; P=.007).
Perspective
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Laurence A. Boxer, MD
Hurler syndrome is a severe form of mucopolysaccharidosis type 1 (MPS1). It is an autosomal recessive disorder caused by a deficiency of the lysosomal hydrolase alpha-L-iduronidase, which is required for the degradation of heparin sulphate and dermatan.
Hurler syndrome is characterized by a broad spectrum of severe clinical disorders, including skeletal abnormalities, hepatosplenomegaly and profound intellectual impairment. It occurs in approximately 1 in 100,000 births. At birth, affected infants appear normal, but during the first year of life they develop coarse facial features. At between 6 months to 2 years of age, they show signs of developmental delay accompanied often by rapidly enlarging head size, heart failure, hernias and gibbus deformity of the lower spine. Often the predisposition to multiple respiratory infections shortens the life span of the affected children. The average age of death is 5 years, and nearly all patients die before age 10.
The paper by Boelens and colleagues describes a collaborative, retrospective analysis of risk factors after hematopoietic stem cell transplantation for Hurler syndrome patients treated at multiple centers worldwide. The transplantation outcomes of 258 affected children represents the largest study yet performed.
At 5 years, OS was 75% and EFS was 63%. Rather dramatically, full donor chimerism and normal enzyme levels of the defective hydrolase were noted to be higher after cord blood transplantation (92% and 98%, respectively) compared with other graft sources (69% and 59%, respectively).
The authors observed that the results of allogeneic transplantation for Hurler’s syndrome were similar in terms of EFS after HLA-matched sibling donors, 6/6 matched unrelated-cord blood, 5/6 unrelated cord blood and 10/10 matched unrelated donors. The authors noted that the EFS was enhanced if the patients underwent transplantation before 17 months of age. These results indicate the need for early referral to transplantation centers for infants diagnosed with Hurler’s syndrome and for families with an index case, which in turn supports the need for perinatal screening. In conclusion, early transplantation — especially with cord blood donors — offers the best hope for improving the lives of children with Hurler’s syndrome.
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