Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis

- The risk for cardiovascular risk factors (CVRFs) increases over time after total body irradiation (TBI) exposure.
- Survivors are at increased risk for high triglyceride and low high-density lipoprotein cholesterol levels compared with controls.
- Our data underscore the importance of CVRF screening after TBI starting in childhood.

Hematopoietic cell transplantation (HCT) survivors treated with total body irradiation (TBI) are known to be at increased risk for the development of cardiovascular risk factors (CVRFs). We sought to characterize the incidence of CVRFs in a TBI-exposed survivor cohort and to describe prognostic indicators of their development through a retrospective analysis of CVRFs in 1-year survivors of leukemia or lymphoma treated with TBI at Memorial Sloan Kettering between April 1987 and May 2011. Eligible participants were age ≤21 years at the time of TBI and were not receiving glucocorticoid therapy at the time of entry to long-term follow-up. Survivors were assessed for obesity (body mass index ≥95th percentile for age ≤ 20 years and ≥30 kg/m2 for age >20 years), elevated blood pressure, dyslipidemia (elevated triglycerides [TG], low high-density lipoprotein [HDL]), and glucose intolerance (fasting glucose ≥100 mg/dL); those with ≥3 risk factors were deemed to have a CVRF cluster, a surrogate for metabolic syndrome. Cox regression models were used to estimate hazard ratios (HRs) for factors associated with each CVRF. To compare the prevalence of CVRFs in HCT survivors and the general population, survivors were compared with age-, sex-, and race-matched controls from the National Health and Nutrition Examination Survey. A total of 123 survivors were evaluated (62.6% males). The median age at TBI was 11.8 years (range, 1.6 to 21.9 years). The median duration of follow-up was 8.0 years (range, 1.01 to 24.6 years), and the median age at last follow-up was 20.1 years (range, 4.0 to 41.3 years). The 5-year cumulative incidence was 14.7% for elevated blood pressure, 10.5% for elevated glucose, 26.8% for low HDL, 39.2% for hypertriglyceridemia, and 16.0% for obesity, and corresponding 10-year cumulative incidences of 28.8%, 33.1%, 52.0%, 65.0%, and 18.6%. The median cumulative incidence of a CVRF cluster rose from 10.6% (range, 5.6% to 17.5%) at 5 years to 28.4% (range, 18.8% to 38.7%) at 10 years. In multivariate analysis, growth hormone (GH) deficiency (hazard ratio [HR], 8.6; 95% confidence interval [CI], 2.1 to 34.4; P = .002), history of cranial radiation (HR, 4.0; 95% CI, 1.7 to 9.6; P = .002), and grade II-IV acute graft-versus-host disease GVHD (HR, 4.2; 95% CI, 1.5 to 12.2; P = .008) were associated with the risk of developing a CVRF cluster. Compared with a random sample of matched population controls, HCT survivors had an increased prevalence of hypertriglyceridemia and low HDL, but not of glucose intolerance, elevated blood pressure, or CVRF cluster. Given the young age of this HCT survivor cohort, these data highlight the importance of routine screening for CVRF starting in childhood in individuals exposed to TBI.