Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study.

Abstract

Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outcome of patients with MPS-IH after HCT are lacking. The goal of this international study was to identify predictors of the long-term outcome of patients with MPS-IH after successful HCT. Two hundred seventeen patients with MPS-IH successfully engrafted with a median follow-up age of 9.2 years were included in this retrospective analysis. Primary endpoints were neurodevelopmental outcomes and growth. Secondary endpoints included neurologic, orthopedic, cardiac, respiratory, ophthalmologic, audiologic, and endocrinologic outcomes. Considerable residual disease burden was observed in the majority of the transplanted patients with MPS-IH, with high variability between patients. Preservation of cognitive function at HCT and a younger age at transplantation were major predictors for superior cognitive development posttransplant. A normal α-l-iduronidase enzyme level obtained post-HCT was another highly significant predictor for superior long-term outcome in most organ systems. The long-term prognosis of patients with MPS-IH receiving HCT can be improved by reducing the age at HCT through earlier diagnosis, as well as using exclusively noncarrier donors and achieving complete donor chimerism.

• Authors: Mieke Aldenhoven, Robert F Wynn, Paul J Orchard, Anne O'Meara, Paul Veys, Alain Fischer, Vassili Valayannopoulos, Benedicte Neven, Attilio Rovelli, Vinod K Prasad, Jakub Tolar, Heather Allewelt, Simon A Jones, Rossella Parini, Marleen Renard, Victoria Bordon, Nico M Wulffraat, Tom J de Koning, Elsa G Shapiro, Joanne Kurtzberg, Jaap Jan Boelens
• Journal: Blood (Blood) Vol. 125 Issue 13 Pg. 2164-72 (Mar 26 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25624320 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Topics

• Adolescent
• Adult
• Child
• Child Development
• Child, Preschool
• Cognition
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation (statistics & numerical data)
• Humans
• Infant
• Infant, Newborn
• Male
• Mucopolysaccharidosis I (epidemiology, physiopathology, psychology, therapy)
• Retrospective Studies
• Treatment Outcome
• Young Adult