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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)

Wadhwa, Aman; Chen, Yanjun; Holmqvist, Anna LU ; Wu, Jessica; Ness, Emily; Parman, Mariel; Kung, Michelle; Hageman, Lindsey; Francisco, Liton and Braunlin, Elizabeth, et al. (2019) In Biology of Blood and Marrow Transplantation 25(2). p.328-334
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... (More)

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.

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publication status
published
subject
keywords
Blood or marrow transplantation, Inborn errors of metabolism, Late mortality
in
Biology of Blood and Marrow Transplantation
volume
25
issue
2
pages
328 - 334
publisher
Elsevier
external identifiers
  • scopus:85055984880
ISSN
1083-8791
DOI
10.1016/j.bbmt.2018.09.035
language
English
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yes
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ea1df8df-7d25-4058-b1cf-68330e518306
date added to LUP
2018-11-23 13:37:29
date last changed
2019-11-13 05:21:20
@article{ea1df8df-7d25-4058-b1cf-68330e518306,
  abstract     = {<p>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.</p>},
  author       = {Wadhwa, Aman and Chen, Yanjun and Holmqvist, Anna and Wu, Jessica and Ness, Emily and Parman, Mariel and Kung, Michelle and Hageman, Lindsey and Francisco, Liton and Braunlin, Elizabeth and Miller, Weston and Lund, Troy and Armenian, Saro and Arora, Mukta and Orchard, Paul and Bhatia, Smita},
  issn         = {1083-8791},
  keyword      = {Blood or marrow transplantation,Inborn errors of metabolism,Late mortality},
  language     = {eng},
  number       = {2},
  pages        = {328--334},
  publisher    = {Elsevier},
  series       = {Biology of Blood and Marrow Transplantation},
  title        = {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)},
  url          = {http://dx.doi.org/10.1016/j.bbmt.2018.09.035},
  volume       = {25},
  year         = {2019},
}