Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.
PURPOSE To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies. PATIENTS AND METHODS Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population. RESULTS A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors. CONCLUSION The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.
Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; = .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.
Hemostatic complications are commonly encountered in blood or marrow transplantation (BMT) recipients, increasing their morbidity and mortality and are well described in the immediate post-transplantation period. The risk of venous thromboembolism (VTE) in long-term survivors of autologous BMT has not been studied previously. Patients who underwent autologous BMT between January 1, 1974, and December 31, 2010 for a hematologic malignancy, lived 2 years or more after transplantation, and were age 18 years were surveyed for longterm outcomes. The median duration of follow-up was 9.8 years (interquartile range, 6.4 to 14.3 years). We analyzed the risk of VTE in 820 autologous BMT recipients who survived for 2 years, compared with 644 siblings. BMT survivors were at a 2.6-fold higher risk of VTE compared with siblings (95% confidence interval [CI], 1.6 to 4.4; P =.0004), after adjusting for sociodemographic characteristics. Conditional on surviving for 2 years after BMT, the mean cumulative incidence of VTE was 3.9 § .8% at 5 years and 6.1 § 1.1% at 10 years. A diagnosis of plasma cell disorder (hazard ratio [HR], 2.37; 95% CI, 1.3 to 4.2; P = .004) and annual household income $50,000 (HR, 2.02; 95% CI, 1.2 to 3.6; P = .015) were associated with increased VTE risk. Our data indicate that autologous BMT survivors are at elevated risk for developing late-occurring VTE. The development of risk prediction models to identify autologous BMT survivors at greatest risk for VTE and thromboprophylaxis may help decrease the morbidity and mortality associated with VTE.
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