Cancer and Post-therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults with Down Syndrome

The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4 years in 1970 to 53 years in 2010. Despite the recent improvement in survival, there is little data about the prevalence of age-related diseases, including age-related malignancies, and the impact of standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age- and sex-matched patients ≥15 years old with and without Down syndrome using the TriNetX platform to identify the prevalence of malignancies and explore cardiovascular outcomes after treatment with anthracyclines. We further stratified the populations into adolescent and young adult (AYA, ages 15-39 years old) and adult (≥40 years old) cohorts, given that treatment recommendations can be different. Down syndrome patients in the AYA cohort were more likely to be diagnosed with acute myeloid (OR 8.9, CI 4.99-15.89, p<0.001) and lymphoid (OR 7.33, CI 4.82-11.15, p<0.001) leukemia. The adult cohort with Down syndrome was more likely to be diagnosed with myelodysplastic syndromes (OR 12.25, CI 6.41-23.42, p<0.001), multiple myeloma (OR 1.66, CI 1.06-2.6, p=0.026), and testicular cancer (OR 2.73, CI 1.32-5.65, p=0.005). Overall, Down syndrome patients (≥15 years old) treated with anthracyclines were more likely to be diagnosed with heart failure (OR 2.14, CI 1.07-4.27, p=0.042). Our study demonstrates adolescents and adults with Down syndrome have a higher predisposition to several malignancies and an increased risk of cardiovascular disease after anthracycline treatment and may require specific screening guidelines to address their unique health risks.