Late mortality after autologous blood or marrow transplantation in childhood: a Blood or Marrow Transplant Survivor Study-2 report.

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%; P = .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.

Venous Thromboembolism in Autologous Blood or Marrow Transplantation Survivors: A Report from the Blood or Marrow Transplant Survivor Study.

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 long-term 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.

Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia.

Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and evaluating how this risk differs between these diseases. We investigated cause-specific late mortality in 2-year survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22years between 1974 and 2010 at 2 US transplantation centers. Vital status information was collected from medical records, the National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. The standardized mortality ratio (SMR) was calculated using age- sex-, and calendar-specific mortality rates from the Centers for Disease Control and Prevention. Among the 2-year survivors of bone marrow failure syndromes (n = 120) and SAA (n = 147), there were 15 and 19 deaths, respectively, yielding an overall survival of 86.4% for bone marrow failure syndromes and 93.1% for SAA at 15years post-BMT. Compared with the general population, patients with bone marrow failure syndromes were at a higher risk for premature death (SMR, 22.7; 95% CI, 13.1 to 36.2) compared with those with SAA (SMR, 4.5; 95% CI, 2.8 to 7.0) (P < .0001). The elevated relative risk persisted at ≥15years after BMT for both diseases. The hazard of all-cause late mortality was 2.9-fold (95% CI, 1.1 to 7.3) higher in patients with bone marrow failure syndromes compared with those with SAA. The high late mortality risk in recipients of allogeneic BMT in childhood for bone marrow failure syndromes calls for intensified life-long follow-up.

Impact of access to care on 1-year mortality following allogeneic blood or marrow transplantation.

Mortality is highest in the first year following an allogeneic hematopoietic stem cell transplant. With recent advancements, we have expanded the pool of patients to whom we are able to offer transplant as a treatment option. In this context, we analyzed socioeconomic, patient, disease and transplant-related variables that predicted for 1-year all-cause, relapse-related (RRM) and non-relapse related mortality (NRM) in 304 patients at the University of Alabama at Birmingham. The 1-year overall survival, RRM and NRM rates were 60.5%, 13.5% and 22.7% respectively. A KPS score < 80, pre-transplant infection and hypertension and non-complete remission disease status adversely effected all-cause mortality. For NRM, increasing age, pre-transplant infection and diabetes, and poor access to care were associated with higher mortality whereas haploidentical donor type was associated with improved survival. For RRM, a KPS score <80, high/very high disease risk index and the presence of comorbidities were risk factors for higher mortality. Poor access to care, in addition to individual comorbidities, performance status and high-risk disease characteristics, is associated with adverse outcomes following transplant. We propose the incorporation of socioeconomic variables with patient, disease, and transplant-related variables to predict 1-year NRM.

Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report.

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.

Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood.

Importance: Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives: To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants: A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure: Allogeneic BMT performed in childhood. Main Outcomes and Measures: All-cause mortality, relapse-related mortality, and non-relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results: Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P = .002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P = .007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P = .002; P < .001 for trend). Conclusions and Relevance: 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.