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Original Investigation
September 9, 2021

Trends in Late Mortality and Life Expectancy After Allogeneic Blood or Marrow Transplantation Over 4 Decades: A Blood or Marrow Transplant Survivor Study Report

Author Affiliations
  • 1Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham
  • 2Population Sciences, City of Hope, Duarte, California
  • 3Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis
  • 4Division of Hematology, Oncology, and Bone Marrow Transplantation, University of Alabama at Birmingham
  • 5Division of Pediatric Hematology, Oncology, and Bone Marrow Transplantation, University of Alabama at Birmingham
JAMA Oncol. Published online September 9, 2021. doi:10.1001/jamaoncol.2021.3676
Key Points

Question  What are the trends in life expectancy and cause-specific late mortality after allogeneic blood or marrow transplantation over a 40-year period?

Findings  This cohort study of 4741 individuals 2 years after allogeneic blood or marrow transplantation performed between 1974 and 2014 found that, although late mortality declined, life expectancy was not fully restored to expected rates in the general US population. However, the decline in late mortality appeared to be limited to transplants performed in childhood or with bone marrow as a stem cell source, without meaningful declines for older patients or for those who received peripheral blood stem cell transplant.

Meaning  The findings of this study suggest that efforts to mitigate causes may be useful to reduce late mortality after blood or marrow transplantation.

Abstract

Importance  The past 4 decades have seen substantial changes in allogeneic blood or marrow transplantation (BMT) practice, with the overarching goal of expanding the eligible patient pool while optimizing disease-free survival.

Objective  To determine trends in life expectancy and cause-specific late mortality after allogeneic BMT performed over a 40-year period.

Design, Setting, and Participants  A retrospective cohort study of 4741 individuals who lived 2 or more years after allogeneic BMT performed between January 1, 1974, and December 31, 2014, was conducted at City of Hope, University of Minnesota, or University of Alabama at Birmingham. The end of follow-up was March 23, 2020.

Exposures  Allogeneic BMT performed in 3 eras: 1974-1989, 1990-2004, and 2005-2014.

Main Outcomes and Measures  All-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Information regarding vital status and cause of death was obtained from the National Death Index Plus and Accurint databases.

Results  Of the 4741 individuals included in the study, 2735 (57.7%) were male; median age at BMT was 33 years (range, 0-75 years). The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% (95% CI, 11.0%-13.4%) at 30 years from BMT. In contrast, the incidence of nonrecurrence-related mortality continued to increase and was 22.3% (95% CI, 20.4%-24.3%) at 30 years. Leading causes of nonrecurrence-related mortality included infection (30-year cumulative incidence, 10.7%; standardized mortality ratio [SMR], 52.0), subsequent malignant neoplasms (30-year cumulative incidence, 7.0%; SMR, 4.8), cardiovascular disease (30-year cumulative incidence, 4.6%; SMR, 4.1), and pulmonary disease (30-year cumulative incidence, 2.7%; SMR, 13.9). Compared with the general population, the relative mortality remained higher at 30 or more years after BMT (SMR, 5.4; 95% CI, 4.0-7.1). The cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost). Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio (HR) of all-cause mortality declined over the 3 eras (1990-2004: HR, 0.67; 95% CI, 0.53-0.85; 2005-2014: HR, 0.52; 95% CI, 0.39-0.69; P < .001 for trend), as did years of life lost (1974-1989: 9.9 years [reference]; 1990-2004: 6.5 years; and 2005-2014: 4.2 years). The reduction in late mortality was most pronounced among individuals who underwent transplantation at ages younger than 18 years (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; reference: 1974-1989; P < .001 for trend) and those who received bone marrow (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR, 0.45; 95% CI, 0.29-0.69; reference: 1974-1989; P < .001 for trend).

Conclusions and Relevance  This cohort study noted that late mortality among recipients of allogeneic BMT has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general US population. Furthermore, the reduction in risk of late mortality appeared to be confined to those who underwent transplantation at a younger age or those who received bone marrow. Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population.

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