title: 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.affiliation: Blood and Marrow Transplantation Program, Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands;
authors.forename: Mieke
authors.initials: M
authors.lastname: Aldenhoven
authors.affiliation: Blood and Marrow Transplant Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom;
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wynn
authors.affiliation: Program in Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN;
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Our Lady's Children's Hospital, Dublin, Ireland;
authors.forename: Anne
authors.initials: A
authors.lastname: O'Meara
authors.affiliation: Blood and Marrow Transplantation Program, Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Département de Biothérapie and.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Reference Center for Inherited Metabolic Diseases and Imagine Institute, Assistance Publique-Hopiteaux de Paris, Hôpital Universitaire Necker-Enfants Malades, Paris, France;
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.affiliation: Département de Biothérapie and.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Neven
authors.affiliation: Pediatric Bone Marrow Transplant Unit, Department of Pediatrics, San Gerardo University Hospital, Monza, Italy;
authors.forename: Attilio
authors.initials: A
authors.lastname: Rovelli
authors.affiliation: The Pediatric Blood and Marrow Transplant Program, Duke University, Durham, NC;
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Prasad
authors.affiliation: Program in Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN;
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: The Pediatric Blood and Marrow Transplant Program, Duke University, Durham, NC;
authors.forename: Heather
authors.initials: H
authors.lastname: Allewelt
authors.affiliation: Willink Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals, University of Manchester, Manchester, United Kingdom;
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Rare Metabolic Disorders Unit, Department of Pediatrics, San Gerardo University Hospital, Monza, Italy;
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.affiliation: Pediatric Hematology and Oncology, University Hospital Leuven, Leuven, Belgium;
authors.forename: Marleen
authors.initials: M
authors.lastname: Renard
authors.affiliation: Pediatric Hematology and Oncology, Ghent University Hospital, Ghent, Belgium;
authors.forename: Victoria
authors.initials: V
authors.lastname: Bordon
authors.affiliation: Department of Pediatric Immunology and Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands;
authors.forename: Nico M
authors.initials: NM
authors.lastname: Wulffraat
authors.affiliation: University Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; and.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: de Koning
authors.affiliation: Department of Pediatrics and Neurology, Division of Clinical Behavioral Neuroscience, University of Minnesota, Minneapolis, MN.
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
authors.affiliation: The Pediatric Blood and Marrow Transplant Program, Duke University, Durham, NC;
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.affiliation: Blood and Marrow Transplantation Program, Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands;
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Boelens
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008059:Mucopolysaccharidosis I / Q000453:epidemiology / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult