In an analysis from a Blood or Marrow Transplant Survivor Study cohort reported in JAMA Oncology, Smita Bhatia, MD, MPH, and colleagues found that late mortality among patients undergoing allogeneic blood or marrow transplantation for hematologic malignancies has declined over the past 40 years, although life expectancy still remained reduced compared with the general population.
Smita Bhatia, MD, MPH
Study Details
The study included data from 4,741 patients who survived for at least 2 years after allogeneic blood or marrow transplantation performed between January 1974 and December 2014 at City of Hope, the University of Minnesota, or the University of Alabama at Birmingham. Follow-up ended in March 2020. Comparisons of outcomes were performed for three eras: 1974 to 1989, 1990 to 2004, and 2005 to 2014. Standardized mortality ratios (SMRs) were used to compare mortality in the cohort with age-, sex- and calendar-specific mortality in the U.S. population.
Key Findings
The cumulative incidence curve of recurrence-related mortality plateaued at 10 years, with cumulative incidence reaching 12.2% (95% confidence interval [CI] = 11.0%–13.4%) at 30 years after blood or marrow transplantation.
The cumulative incidence of non–recurrence-related mortality exhibited a steady increase, reaching 22.3% (95% CI = 20.4%–24.3%) at 30 years. Cumulative incidence of mortality at 30 years was 10.7% due to infection (SMR = 52.0), 7.0% due to subsequent malignant neoplasms (SMR = 4.8), 4.6% due to cardiovascular disease (SMR = 4.1), and 2.7% due to pulmonary disease (SMR = 13.9).
Overall, the cohort had an 8.8-fold higher risk for all-cause mortality compared with the general population. Increased risk was greatest at 2 to 5 years after blood or marrow transplantation (SMR = 34.3, 95% CI = 31.7–36.9), decreasing thereafter but remaining significant at ≥ 30 years (SMR = 5.4, 95% CI = 4.0–7.1). Relative mortality significantly declined between 1974 and 1989 (SMR = 23.4) and 2005 and 2014 (SMR = 5.8, P < .001). Overall, the cohort had a 20.8% reduction in life expectancy, equivalent to 8.7 years of life lost.
Photo credit: Getty
Compared with 1974 to 1989, the adjusted hazard ratios (HRs) for 10-year all-cause mortality were 0.67 (95% CI = 0.53–0.85) for 1990 to 2004 and 0.52 (95% CI = 0.39–0.69) for 2005 to 2014 (P < .001 for trend). Years of life lost were 9.9 for 1974 to 1989, decreasing to 6.5 (HR = 0.67, 95% CI = 0.53–0.85) for 1990 to 2004 and 4.2 (HR = 0.52, 95% CI = 0.39–0.69) for 2005 to 2014 (P < .001 for trend).
The reduction in late mortality compared with that for 1974 to 1989 was predominantly driven by outcomes in two subgroups: patients undergoing blood or marrow transplantation at age < 18 years, with hazard ratios of 0.62 (95% CI = 0.40–0.96) for 1990 to 2004 and 0.30 (95% CI = 0.16–0.54) for 2005 to 2014 (P < .001 for trend); and patients who received bone marrow, with hazard ratios of 0.70 (95% CI = 0.54–0.90) for 1990 to 2004 and 0.45 (95% CI = 0.29–0.69) for 2005 to 2014 (P < .001 for trend).
The investigators concluded, “This cohort study noted that late mortality among recipients of allogeneic blood or marrow transplantation has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general U.S. 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.”
Dr. Bhatia, of the Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and Leukemia and Lymphoma Society. For full disclosures of the study authors, visit jamanetwork.com.
