title: Mortality after hematopoietic stem cell transplantation for severe mucopolysaccharidosis type I: the 30-year University of Minnesota experience.
abstract: Mucopolysaccharidosis IH (MPS IH, Hurler syndrome) naturally leads to death within the first decade of life, primarily from cardiac and pulmonary causes. To determine how hematopoietic stem cell transplantation (HSCT) has altered mortality, we analyzed our institution's 30-year experience of patients with MPS IH undergoing HSCT.
  
  
  
  Using chart review and the National Death Index, we determined survival status of 134 patients (males = 69) with MPS IH transplanted between 9/16/1983 and 7/25/2013 on 12/31/2013. Analysis included descriptive statistics, Kaplan-Meier curves, and regression analysis by Cox proportional hazards model.
  
  
  
  Overall survival (95% CI) at one- and 25-years was 70% (62-78%) and 37% (19-55%), respectively. From 2004 onward, overall survival at one- and 8-years was 84% (73-96%) and 81% (69-94%), respectively, compared to 65% (55-74%) and 57% (47-67%) prior to 2004 (Log-rank p = 0.032). Regardless of era, male survival was significantly better than female (HR 0.40, [95% CI: 0.21-0.74], p = 0.004). The cumulative incidence of death (95% CI) at 25 years was 63% (45-81%); incidence of pulmonary-related death was the highest at 27% (10-41%) compared to 8% (0.3-16%) for cardiac, 12% (6-17%) for infectious disease, and 16% (3-27%) from other complications.
  
  
  
  HSCT has increased survival in MPS IH beyond the third decade of life and decreased the incidence of cardiac mortality, but deaths after the third year post-HSCT occur in excess of expected US mortality. It is important to determine if improved transplant strategies since 2004 result in better long-term survival in the current patient population.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Masonic Children's Hospital, University of Minnesota Medical School, Minneapolis, MN, 55454, USA. rodge184@umn.edu.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Rodgers
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Kaizer
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, Masonic Children's Hospital, University of Minnesota, Minneapolis, MN, 55454, USA.
authors.forename: Weston P
authors.initials: WP
authors.lastname: Miller
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Rudser
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, Masonic Children's Hospital, University of Minnesota, Minneapolis, MN, 55454, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Masonic Children's Hospital, University of Minnesota Medical School, Minneapolis, MN, 55454, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Braunlin
mesh_terms: D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality*; D006801:Humans; D007223:Infant; D008297:Male; D008910:Minnesota; D008059:Mucopolysaccharidosis I / Q000401:mortality*; D012189:Retrospective Studies