Second cancers, cardiovascular disease and quality of life after treatment for large B-cell lymphoma and Hodgkin lymphoma

Advances in treatment of diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL) have significantly increased survival, but have also introduced risks of late effects. The studies in this thesis examined the risk of second malignant neoplasms, cardiovascular diseases and fatigue, neuropathy, psychological distress and health-related quality of life among long-term survivors of lymphoma.
The first part of this thesis evaluates risks of second cancers. In female five-year HL survivors, we demonstrate for the first time that doxorubicin exposure at adolescent and adult ages increases breast cancer risk, independent of chest radiotherapy or age at treatment. In DLBCL five-year survivors we showed increased risks of solid and hematologic malignancies, particularly after higher cumulative doses of cyclophosphamide or doxorubicin.
The second part focuses on cardiovascular diseases. In a five-year DLBCL survivor cohort, risks of heart failure and cerebrovascular accident were increased compared with the general population for over twenty years; particularly in survivors treated with higher doses of doxorubicin and radiotherapy. The CLARITY cross-sectional study provides detailed echocardiographic and biomarker measurements, demonstrating a high prevalence of subclinical left ventricular dysfunction in five-year survivors compared with a sibling comparison group. We also review emerging evidence on immune checkpoint inhibitor-associated atherosclerosis.
The third part describes that persistent symptoms are frequently reported up to 13 years after diagnosis, substantially affecting health-related quality of life compared with a normative population.
Together, the findings underscore the need for tailored survivorship care, including personalized screening for second cancers and cardiovascular disease, and strategies to address chronic symptoms and improve quality of life among lymphoma survivors.