Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades: A BMTSS Report

Abstract

Purpose: We determined trends in life expectancy and cause-specific late mortality after autologous blood or marrow transplantation (BMT) performed over a 30-year period, using the BMT Survivor Study.

Methods: We constructed a cohort of 4,702 individuals with hematologic neoplasms who lived ≥ 2 years after autologous BMT performed between 1981 and 2014 at three transplant centers. The end of follow-up was April 19, 2021. The primary exposure variable was autologous BMT performed in four eras: 1981-1999; 2000-2005; 2006-2010; and 2011-2014. Vital status and cause of death were obtained from National Death Index Plus program and Accurinct databases.

Results: The median age at BMT was 53 years (range, 0-78 years), 58.7% were male, 67.8% were non-Hispanic White, and 28.3% had undergone transplantation between 2011 and 2014. Autologous BMT recipients experienced a 7-year reduction in life expectancy. The adjusted hazard of 5-year all-cause mortality declined over the four eras (reference: 1981-1999; hazard ratio [HR]_2000-2005 = 0.77; 95% CI, 0.62 to 0.94; HR_2006-2010 = 0.64; 95% CI, 0.51 to 0.79; HR_2011-2014 = 0.56; 95% CI, 0.45 to 0.71; P_trend < .001), as did years of life lost (5.0 years to 1.6 years). The reduction in all-cause mortality was most pronounced among those transplanted for Hodgkin lymphoma or plasma cell dyscrasias, but was not observed among those transplanted for non-Hodgkin lymphoma or those conditioned with total-body irradiation. We also observed a decline in late deaths because of infection (P_trend < .0001; primarily for BMTs before 2006) and subsequent neoplasms (P_trend = .03; confined to decline in therapy-related myeloid neoplasm-related mortality) but not because of cardiovascular or renal disease.

Conclusion: Late mortality among autologous BMT recipients has declined over a 30-year period. However, ongoing efforts are needed to mitigate development of infections, subsequent neoplasms, and cardiovascular and renal disease to further reduce late mortality.

FIG 1.

(A) Mortality rate as a function of time from BMT in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. Empirical mortality rates during each year (solid circles) are shown with fitted rates from the spline-smoothed Poisson regression model (solid line) and associated pointwise 95% CIs (short-dashed lines), and the expected mortality rates for each interval on the basis of sex- and age-specific data for the US population in 2006 (long-dashed line). (B) Mortality rate as a function of age at BMT in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. Empirical annual mortality rates during each 5-year interval of age, plotted at the midpoint of each interval (blue circles), fitted rates from the spline-smoothed Poisson regression model (solid line) and associated pointwise 95% CIs (short-dashed lines), and the expected mortality rates for each interval on the basis of an average of sex-specific US population rates at each age in 2006 (long-dashed lines). BMT, blood or marrow transplantation.

FIG 2.

(A) Absolute reduction in life expectancy by attained age in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. (B) Percent reduction in life expectancy by attained age in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. BMT, blood or marrow transplantation.

FIG 3.

(A) Trends in reduction in life expectancy by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (B) Trends in hazard of all-cause late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (C) Trends in hazard of cause-specific late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (D) Trends in hazards of infection-related late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (E) Trends in hazards of SMN-related late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (F) Trends in hazards of t-MN–related late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation (t-MN). The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (G) Trends in hazards of solid SMN-related late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (H) Trends in hazards of cardiac-related late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. (I) Trends in hazards of renal-related late mortality by transplant era in a cohort of autologous BMT recipients surviving 2 or more years after transplantation. The follow-up was truncated at 5 years post-BMT to allow comparison across the four eras. The models were adjusted for age at transplantation, sex, race/ethnicity, primary diagnosis, disease status at BMT, stem-cell source, and use of TBI. BMT, blood or marrow transplantation; HR, hazard ratio; NRM, non–recurrence-related mortality; RRM, recurrence-related mortality; SMN, subsequent malignant neoplasm; TBI, total body irradiation; t-MN, therapy-related myeloid neoplasm.