Chemotherapy-induced Genomic Damage in Elderly Patients With Lymphoma: Prevalence, Evolution, and Clinical Consequences

Every year approximately 300 Danish patients die from lymphoma. The median age at diagnosis is 70 years. Lymphoma can be efficiently treated with chemotherapy, and potentially cured. However, sufficient treatment is often hampered by toxicity, especially in elderly patients. It is also well known that the main risk factor for dying of lymphoma is age. New biologically targeted therapies with fewer side effects are becoming available for lymphoma treatment, however it is currently difficult to delineate which patients benefit from chemotherapy and which should be treated with novel expensive therapies.

Recently, it has been discovered that chemotherapy can provoke growth of patient blood cells with DNA mutations. This leads to increased rates of treatment side effects and excess mortality. These defects have so far only been examined in younger patients below 70 years of age, where they are found in roughly 10% of patients. It remains unknown to what extent elderly individuals are affected, but the investigators hypothesize that the proportion and negative effects are much larger.

Therefore, the investigators propose to investigate the frequency and evolution of these DNA mutations during chemotherapy in a prospective study of patients, who are either above 60 years of age and previously treated with chemotherapy for lymphoma in a nation-wide collaboration.

By using blood samples, advanced genetic analyses and patient-reported questionnaires, the investigators will study

• The prevalence of these mutations and their consequences for patient wellbeing, treatment side effects (such as anemia, infections etc.) and mortality
• The kinetics of these mutations during and after treatment, and explore possible evolutionary patterns of the inferred damages The investigators expect to include 300 patients in the study and that the first results will be ready in a timeframe of 4 years. The investigators hope to obtain new insights in the risk factors for physiological and mental health in lymphoma patients and thereby pave the way for improvements in wellbeing and survival of this underserved population.