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)

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

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)328-334
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number2
DOIs
StatePublished - Feb 2019

Keywords

  • Blood or marrow transplantation
  • Inborn errors of metabolism
  • Late mortality

PubMed: MeSH publication types

  • Clinical Trial
  • Journal Article
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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