Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 1;7(11):1626-1634.
doi: 10.1001/jamaoncol.2021.3676.

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

Smita Bhatia  1 , Chen Dai  1 , Wendy Landier  1 , Lindsey Hageman  1 , Jessica Wu  1 , Elizabeth Schlichting  1 , Arianna Siler  1 , Erin Funk  1 , Jessica Hicks  1 , Alysia Bosworth  2 , Hok Sreng Te  3 , Liton Francisco  1 , Ravi Bhatia  4 , Donna Salzman  4 , Frederick D Goldman  5 , Stephen J Forman  2 , Daniel J Weisdorf  3 , F Lennie Wong  2 , Mukta Arora  3 , Saro H Armenian  2
Affiliations

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

Smita Bhatia et al. JAMA Oncol. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Weisdorf reported receiving grants from FATE data analysis for end point adjudication and grants from Incyte for collaborative analyses of shared data outside the submitted work. Dr Arora reported participation in a clinical trial on chronic graft-vs-host disease from Syndax, Pharmacyclics, and Kadmon outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Trends in Hazard of All-Cause and Cause-Specific Late Mortality After Allogeneic Blood or Marrow Transplantation (BMT) by Transplant Era
The follow-up was truncated at 10 years post-BMT to allow comparison across the 3 eras. The models were adjusted for age at transplantation, sex, race and ethnicity, primary diagnosis, disease status at BMT, transplant type, stem cell source, conditioning intensity, use of total body irradiation, and presence of chronic graft-vs-host disease. Adjustment showed a decrease for all-cause mortality, recurrence-related mortality, and nonrecurrence-related mortality. The vertical line at 1.0 indicates the reference era (1974-1989). Data markers indicate hazard ratios; whiskers, 95% CIs.
Figure 2.
Figure 2.. Overall Survival by Transplant Era
A, Overall survival by transplant era for patients younger than 18 years at blood or marrow transplantation (BMT). B, Overall survival by transplant era for patients who received bone marrow. Shaded areas indicate 95% CIs.
Figure 3.
Figure 3.. Cumulative Incidence of Mortality
A, Cumulative incidence of recurrence-related mortality (RRM), conditional on surviving the first 2 years after allogeneic blood or marrow transplantation (BMT). B, Cumulative incidence of nonrecurrence-related mortality (NRM), conditional on surviving the first 2 years after allogeneic BMT. Shaded areas indicate 95% CIs.
See this image and copyright information in PMC

Comment in

References

    1. D’Souza A, Fretham C, Lee SJ, et al. . Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2020;26(8):e177-e182. doi:10.1016/j.bbmt.2020.04.013 - DOI - PMC - PubMed
    1. Niederwieser D, Baldomero H, Szer J, et al. . Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. Bone Marrow Transplant. 2016;51(6):778-785. doi:10.1038/bmt.2016.18 - DOI - PMC - PubMed
    1. Majhail NS, Tao L, Bredeson C, et al. . Prevalence of hematopoietic cell transplant survivors in the United States. Biol Blood Marrow Transplant. 2013;19(10):1498-1501. doi:10.1016/j.bbmt.2013.07.020 - DOI - PMC - PubMed
    1. Armenian SH, Sun CL, Francisco L, et al. . Late congestive heart failure after hematopoietic cell transplantation. J Clin Oncol. 2008;26(34):5537-5543. doi:10.1200/JCO.2008.17.7428 - DOI - PMC - PubMed
    1. Armenian SH, Sun CL, Kawashima T, et al. . Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood. 2011;118(5):1413-1420. doi:10.1182/blood-2011-01-331835 - DOI - PMC - PubMed

Publication types