Long-term cardiac morbidity in adolescent and young adult survivors of classical Hodgkin lymphoma: the British Columbia experience

Adolescents and young adults (AYA) with classic Hodgkin lymphoma (cHL) have excellent survival outcomes, however the late effects of treatment, including cardiovascular disease (CVD), can impact long-term disease-free morbidity and mortality. Using population-level administrative data, we evaluated rates of CVD in 2-year AYA survivors of cHL, aged 16-39 years, treated with ABVD or equivalent chemotherapy, with or without radiotherapy (RT). With a median follow up of 17 years (range 2.3-29 years), risk of CVD was 2.9-fold higher relative to controls, with a 5.2-fold risk of heart failure (HF) and 2.4-fold risk of ischemic heart disease (IHD). Risk of HF was associated with anthracycline-containing chemotherapy regimens alone or with combined modality therapy; whereas higher IHD risk was identified only in those treated with RT. At 20 years after the most recent cHL diagnosis or relapse, the cumulative incidence (CI) of HF was 4.3% in cases vs 0.8% in controls; and for IHD was 8.3% in cases vs 2.8% in controls. Treatment after 2005 using a PET scan guided approach reduced the overall use of RT (56.0% < 2005 vs 14.9% > 2005), and was associated with a lower 15-year CI of IHD (< 2005: 3.4% (95% CI 1.8-5.1%), > 2005: 0.7% (95% CI 0-1.7%) with the latter era comparable to controls; (1.6% (95% CI 1.3-1.9%)). cHL survivors had increased 20-year cumulative mortality above that of age-matched controls (5.0% vs 2.0%). These results can inform surveillance strategies, screening guidelines, and recommendations for risk factor modification for AYA cHL survivors.