Abstract
Objectives: Hurler syndrome is characterized by progressive multisystem deterioration leading to early death in childhood. This prospective study evaluated the long-term outcomes of patients with Hurler syndrome who underwent umbilical cord blood transplantation from unrelated donors.
Study design: Only patients with Hurler syndrome who underwent umbilical cord blood transplantation between December 1995 and March 2006 (n = 25) and who were followed for at least 5 years (n = 19) were included in the analysis. The patients were longitudinally evaluated by a multidisciplinary team of specialists following a standardized protocol.
Results: Median age at transplantation was 15.9 months (range 2.1–35), and patients were followed up until a median age of 10.1 years (range 7.2–14.9). Overall survival was 80%. All successfully transplanted patients achieved full donor chimerism and normal enzyme levels, and all children continue to make gains in development. Gross motor function was the most affected area. Vision and hearing were compromised in a minority of the patients, with some requiring corneal transplant or hearing aids. Cardiopulmonary function improved. Some children required orthopedic surgery, but severe complications were prevented in most patients. Although longitudinal growth was lower than that of unaffected children, it was considerably higher than expected from the natural course of the disease. Head circumference normalized. Hydrocephalus was not observed at longer follow-up, and cerebral atrophy decreased over time.
Conclusions: In this descriptive study of children with Hurler syndrome, unrelated umbilical cord blood transplantation was associated with improved somatic disease and neurodevelopment.
Competing interests: None declared
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Acknowledgments
We would like to acknowledge the families who travelled for the evaluation, some of which self-referred for follow-up, and all the clinicians at the University of North Carolina, University of Minnesota, and Duke University Medical Center who participated in the care of these patients. This study was funded by the Caterina Marcus Foundation.
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Communicated by: Pascale de Lonlay
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Synopsis
Unrelated umbilical cord transplantation is associated with improved cognitive development and cardiopulmonary function, attenuated vision and hearing impairment, and prevention of hydrocephalus and severe orthopedic complications.
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Hannah Y. Coletti, Mieke Aldenhoven, Karina Yelin, Michele D. Poe, Joanne Kurtzberg, and Maria L. Escolar declare that they have no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients included in the study.
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HYC and KY collected and entered the data and drafted the initial manuscript; MLE was the principal investigator of the study and secured funding; MA and MLE finished the manuscript; MDP performed statistical analysis; MLE interpreted the results; and JK and MLE critically revised the manuscript.
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Coletti, H.Y., Aldenhoven, M., Yelin, K., Poe, M.D., Kurtzberg, J., Escolar, M.L. (2014). Long-Term Functional Outcomes of Children with Hurler Syndrome Treated with Unrelated Umbilical Cord Blood Transplantation. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 20. JIMD Reports, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_395
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DOI: https://doi.org/10.1007/8904_2014_395
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