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

Research output: Contribution to journalArticle

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 andayoungerageat transplantationweremajorpredictors for superior cognitivedevelopmentposttransplant. Anormal a-L-iduronidase enzyme level obtained post-HCT was another highly significant predictor for superior long-term outcome in most organ systems. The long-termprognosisofpatientswithMPS-IH receivingHCTcanbe improvedbyreducingtheage atHCTthroughearlierdiagnosis, aswell as using exclusively noncarrier donors and achieving complete donor chimerism. (Blood. 2015;125(13):2164-2172)

Details

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
  • Elsa G. Shapiro
  • Joanne Kurtzberg
  • Jaap Jan Boelens
External organisations
  • University Medical Center Utrecht
  • Royal Manchester Children's Hospital
  • University of Minnesota
  • Our Lady's Hospital for Sick Children
  • Royal Free Hospital
  • Necker-Enfants Malades Hospital
  • San Gerardo Hospital
  • Duke University
  • Central Manchester University Hospitals
  • University Hospitals Leuven
  • Ghent University Hospital
  • University Medical Center Groningen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Surgery
Original languageEnglish
Pages (from-to)2164-2172
Number of pages9
JournalBlood
Volume125
Issue number13
Publication statusPublished - 2015 Mar 26
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes