title: Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines.
abstract: Allogeneic hematopoietic cell transplantation (HCT) is the only treatment able to prevent progressive neurodegenerative disease in a selected group of mucopolysaccharidosis (MPS) disorders. However, its use was historically limited by the high risk of graft failure and transplantation-related morbidity and mortality. Therefore, since 2005 new international HCT guidelines for MPS disorders were proposed. The survival and graft outcomes of MPS patients receiving HCT according to these guidelines in 2 European centers of expertise were evaluated. Two consecutive conditioning regimens were used, busulfan/cyclophosphamide or fludarabine/busulfan-based, both with exposure-targeted i.v. busulfan. A noncarrier matched sibling donor (MSD), matched unrelated cord blood (UCB), or matched unrelated donor (MUD) were considered to be preferred donors. If not available, a mismatched UCB donor was used. Participants were 62 MPS patients (56 MPS type I-Hurler, 2 MPS type II, 2 MPS type III, and 2 MPS type VI) receiving HCT at median age 13.5 months (range, 3 to 44). Forty-one patients received a UCB donor, 17 MSD, and 4 MUD. High overall survival (95.2%) and event-free survival (90.3%) were achieved with only low toxicity: 13.3% acute graft-versus-host disease aGVHD) grades II to IV and 14.8% chronic GVHD (1.9% extensive). A mismatched donor predicted for lower event-free survival (P = .04). A higher age at HCT was a predictor for both aGVHD (P = .001) and chronic GVHD (P = .01). The use of a mismatched donor was a predictor for aGVHD (P = .01). Higher rates of full-donor chimerism were achieved in successfully transplanted UCB recipients compared with MSD/MUD (P = .002). If complying with the international HCT guidelines, HCT in MPS patients results in high safety and efficacy. This allows extension of HCT to more attenuated MPS types. Because a younger age at HCT is associated with reduction of HCT-related toxicity, newborn screening may further increase safety.
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mieke
authors.initials: M
authors.lastname: Aldenhoven
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: Blood and Marrow Transplant Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom.
authors.forename: Denise
authors.initials: D
authors.lastname: Bonney
authors.affiliation: Blood and Marrow Transplant Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom.
authors.forename: Roisin E
authors.initials: RE
authors.lastname: Borrill
authors.affiliation: Blood and Marrow Transplant Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Coussons
authors.affiliation: Willink Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals, University of Manchester, Manchester, United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: Mercer
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bierings
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Versluys
authors.affiliation: Department of Metabolic Disorders, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: van Hasselt
authors.affiliation: Department of Pediatrics and Amsterdam Lysosome Centre "Sphinx", University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ans T
authors.initials: AT
authors.lastname: van der Ploeg
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: Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: j.j.boelens@umcutrecht.nl.
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Boelens
mesh_terms: D000208:Acute Disease; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009083:Mucopolysaccharidoses / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D017410:Practice Guidelines as Topic; D011379:Prognosis; D012008:Recurrence; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Hematopoietic cell transplantation; Hurler syndrome; Mucopolysaccharidosis