Cumulative Burden of Cardiovascular Morbidity among Pediatric, Adolescent and Young Adult Hodgkin Lymphoma Survivors: An Analysis from the St. Jude Lifetime Cohort Study

BACKGROUND: The magnitude of cardiovascular morbidity among survivors of pediatric, adolescent, and young adult Hodgkin lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions among Hodgkin survivors and general population controls. METHODS: Among 670 survivors treated at St. Jude Children’s Research Hospital, who survived ≥10 years and became 18 years old, 348 were clinically assessed in the St. Jude Lifetime Cohort Study (SJLIFE). Age-sex-frequency-matched SJLIFE community-controls (n=272) were used for comparison. All SJLIFE participants underwent evaluation for 22 chronic cardiovascular health conditions. Direct assessments, combined with retrospective clinical reviews, were used to assign severity to conditions using a modified Common Terminology Criteria of Adverse Events (CTCAE) grading schema. Occurrences and CTCAE-grades of the conditions for 322 eligible non-SJLIFE participants were accounted for by multiple imputation. The mean cumulative count (treating death as a competing risk) was used to estimate cumulative burden. FINDINGS: At 50 years of age, the cumulative incidence of survivors experiencing at least one grade 3-5 cardiovascular condition was 45.5%. The survivor cohort experienced, on average, 430·6 (95% confidence interval, 380·7-480·6) grade 1-5 and 100·8 (77·3-124·3) grade 3-5 cardiovascular conditions per 100 survivors. At age 50, the grade 1-5 and 3-5 cumulative burdens of community-controls were appreciably lower at 227·4/100 (192·7-267·5) and 17·0/100 (8·4-27·5), respectively. Myocardial infarction and structural heart defects were the major contributors to the excess grade 3-5 cumulative burden among survivors. Higher cardiac radiation dose (≥35 Gy) was associated with an increased grade 3-5 cardiovascular burden. INTERPRETATION: The true impact of cardiovascular morbidity among pediatric Hodgkin lymphoma survivors is reflected in the cumulative burden. 50-year-old Hodgkin survivors will experience over two times the number of chronic cardiovascular health conditions compared community-controls and, on average, have one severe/life-threatening/fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach to evaluating overall morbidity and will assist clinical researchers when designing future trials and refining general practice screening guidelines.