title: Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10 year combined experience of 2 centres.
abstract: Haematopoietic stem cell transplantation is the treatment of choice for the severe form of Mucopolysaccharidosis Type I, or Hurler syndrome. In many centres standard practice is to deliver enzyme replacement therapy alongside haematopoietic stem cell transplantation to improve the condition of the patient prior to transplant. We report the combined 10 year experience of this approach in two paediatric metabolic and transplant centres. Of 81 patients who underwent a first transplant procedure for Hurler, 88% (71/81) survived and 81% (66/81) were alive and engrafted at a median follow-up of 46 months (range 3-124 months). The incidence of grade II-IV acute and any chronic graft versus host disease was 17% and 11% respectively. Urinary glycosaminoglycans were significantly reduced after a period of enzyme replacement therapy, and further reductions were seen at 13-24 months and 25+months after transplantation. In several individuals with decreased cardiac contractility, an improvement of their condition during enzyme replacement therapy enabled them to undergo transplantation, with one individual receiving full intensity conditioning.
authors.affiliation: Manchester Centre For Genomic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK; MPS Stem Cell and Neuropathies, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Electronic address: arunabha.ghosh@cmft.nhs.uk.
authors.forename: Arunabha
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. Electronic address: mill4991@umn.edu.
authors.forename: Weston
authors.initials: W
authors.lastname: Miller
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. Electronic address: orcha001@umn.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Manchester Centre For Genomic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK. Electronic address: simon.jones@cmft.nhs.uk.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Manchester Centre For Genomic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK. Electronic address: jean.mercer@cmft.nhs.uk.
authors.forename: Jean
authors.initials: J
authors.lastname: Mercer
authors.affiliation: Manchester Centre For Genomic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK. Electronic address: heather.church@cmft.nhs.uk.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Church
authors.affiliation: Manchester Centre For Genomic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK. Electronic address: karen.tylee@cmft.nhs.uk.
authors.forename: Karen
authors.initials: K
authors.lastname: Tylee
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. Electronic address: lundx072@umn.edu.
authors.forename: Troy
authors.initials: T
authors.lastname: Lund
authors.affiliation: MPS Stem Cell and Neuropathies, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Electronic address: brian.bigger@manchester.ac.uk.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Bigger
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. Electronic address: tolar003@umn.edu.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Bone Marrow Transplantation Unit, Royal Manchester Children's Hospital, Oxford Road, Manchester M13 9WL, UK. Electronic address: robert.wynn@cmft.nhs.uk.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wynn
mesh_terms: D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000628:therapy*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006025:Glycosaminoglycans; D007068:Iduronidase
keywords: Enzyme replacement therapy; Haematopoietic stem cell transplantation; Hurler syndrome; Mucopolysaccharidosis Type I; Outcome
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