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 A Braunlin, Weston Miller, Troy C Lund, Saro Armenian, Mukta Arora, Paul J Orchard, Smita Bhatia

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 1 2019

Fingerprint

Inborn Errors Metabolism
Survivors
Transplantation
Bone Marrow
Transplants
Mortality
Mucopolysaccharidosis I
Confidence Intervals
Survival
Disease Progression
Metachromatic Leukodystrophy
Adrenoleukodystrophy
Busulfan
Standard of Care
Cyclosporine
T-Lymphocytes

Keywords

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

PubMed: MeSH publication types

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

Cite this

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; Wu, Jessica; Ness, Emily; Parman, Mariel; Kung, Michelle; Hageman, Lindsey; Francisco, Liton; Braunlin, Elizabeth A; Miller, Weston; Lund, Troy C; Armenian, Saro; Arora, Mukta; Orchard, Paul J; Bhatia, Smita.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 2, 01.02.2019, p. 328-334.

Research output: Contribution to journalArticle

Wadhwa, Aman ; Chen, Yanjun ; Holmqvist, Anna ; Wu, Jessica ; Ness, Emily ; Parman, Mariel ; Kung, Michelle ; Hageman, Lindsey ; Francisco, Liton ; Braunlin, Elizabeth A ; Miller, Weston ; Lund, Troy C ; Armenian, Saro ; Arora, Mukta ; Orchard, Paul J ; Bhatia, Smita. / 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). In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 2. pp. 328-334.
@article{bc672cf4e3684754ac0fc283bca40588,
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)",
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.",
keywords = "Blood or marrow transplantation, Inborn errors of metabolism, Late mortality",
author = "Aman Wadhwa and Yanjun Chen and Anna Holmqvist and Jessica Wu and Emily Ness and Mariel Parman and Michelle Kung and Lindsey Hageman and Liton Francisco and Braunlin, {Elizabeth A} and Weston Miller and Lund, {Troy C} and Saro Armenian and Mukta Arora and Orchard, {Paul J} and Smita Bhatia",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.bbmt.2018.09.035",
language = "English (US)",
volume = "25",
pages = "328--334",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Late Mortality after Allogeneic Blood or Marrow Transplantation for Inborn Errors of Metabolism

T2 - A Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2)

AU - Wadhwa, Aman

AU - Chen, Yanjun

AU - Holmqvist, Anna

AU - Wu, Jessica

AU - Ness, Emily

AU - Parman, Mariel

AU - Kung, Michelle

AU - Hageman, Lindsey

AU - Francisco, Liton

AU - Braunlin, Elizabeth A

AU - Miller, Weston

AU - Lund, Troy C

AU - Armenian, Saro

AU - Arora, Mukta

AU - Orchard, Paul J

AU - Bhatia, Smita

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - Blood or marrow transplantation

KW - Inborn errors of metabolism

KW - Late mortality

UR - http://www.scopus.com/inward/record.url?scp=85055984880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055984880&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2018.09.035

DO - 10.1016/j.bbmt.2018.09.035

M3 - Article

C2 - 30292746

AN - SCOPUS:85055984880

VL - 25

SP - 328

EP - 334

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 2

ER -