Late Mortality after Allogeneic Blood or Marrow Transplantation for Inborn Errors of Metabolism: A Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2)

Research output: Contribution to journalArticle


Allogeneic blood or marrow transplantation (BMT) is currently considered the standard of care for patients with specific inborn errors of metabolism (IEM). However, there is a paucity of studies describing long-term survival and cause-specific late mortality after BMT in these patients with individual types of IEM. We studied 273 patients who had survived ≥2 years after allogeneic BMT for IEM performed between 1974 and 2014. The most prevalent IEM in our cohort were X-linked adrenoleukodystrophy (ALD; 37.3%), Hurler syndrome (35.1%), and metachromatic leukodystrophy (MLD; 10.2%). Conditional on surviving ≥2 years after BMT, the overall survival for the entire cohort was 85.5 ± 2.4% at 10 years and 73.5 ± 3.7% at 20 years. The cohort had a 29-fold increased risk of late death compared with an age- and sex-matched cohort from the general US population (95% CI, 22- to 38-fold). The increased relative mortality was highest in the 2- to 5-year period after BMT (standardized mortality ratio [SMR], 207; 95% confidence interval [CI], 130 to 308) and declined with increasing time from BMT, but remained elevated for ≥21 years after BMT (SMR, 9; 95% CI, 4 to 18). Sequelae from the progression of primary disease were the most common causes of late mortality in this cohort (76%). The use of T cell-depleted grafts in patients with ALD and Hurler syndrome was a risk factor for late mortality. Younger age at BMT and use of busulfan and cyclosporine were protective in patients with Hurler syndrome. Our findings demonstrate relatively favorable overall survival in ≥2-year survivors of allogeneic BMT for IEM, although primary disease progression continues to be responsible for the majority of late deaths.


  • Aman Wadhwa
  • Yanjun Chen
  • Anna Holmqvist
  • Jessica Wu
  • Emily Ness
  • Mariel Parman
  • Michelle Kung
  • Lindsey Hageman
  • Liton Francisco
  • Elizabeth Braunlin
  • Weston Miller
  • Troy Lund
  • Saro Armenian
  • Mukta Arora
  • Paul Orchard
  • Smita Bhatia
External organisations
  • University of Alabama
  • Skåne University Hospital
  • University of Minnesota
  • City of Hope National Medical Center
  • Sangamo Therapeutics
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Hematology


  • Blood or marrow transplantation, Inborn errors of metabolism, Late mortality
Original languageEnglish
Pages (from-to)328-334
JournalBiology of Blood and Marrow Transplantation
Issue number2
Early online date2018 Oct 4
Publication statusPublished - 2019
Publication categoryResearch