Introduction: Cardiovascular toxicity is a well-known complication of both chemotherapy, especially doxorubicin (DXR), and irradiation of the mediastinum for classical Hodgkin lymphoma (cHL). Due to the excellent prognosis in cHL, the mortality rate in late toxicity historically exceeds that of cHL 15 to 20 years after diagnosis, highlighting the need for strategies to minimize toxicity. Our aim was to characterize the incidence of cardiovascular disease (CVD) in our cohort of cHL patients treated with DXR with or without radiotherapy according to standard practice, and to identify any plasma protein associations with pre-existing or emerging CVD post treatment.
Patients and Methods: We analyzed 182 different proteins in 58 biobanked plasma samples from cHL patients using Olink multiplexed panels. The analysis was complemented with separate analyses of NTpro-BNP, Troponin I and CRP. The patient samples were prospectively collected prior to, during and after treatment. Patient charts were reviewed for CVD and risk factors for CVD at diagnosis and after a median follow-up time of 7.8 years. In addition, plasma samples from 60 healthy controls, recruited from the EpiHealth survey, and health related data was collected from patient surveys.
Results: Our analysis showed a statistically significant association between the compound endpoint of heart failure and ischemic heart disease and the protein biomarkers cysteine rich protein 61 (CYR61), glycoprotein nonmetastatic melanoma protein B (GPNMB) and activated leukocyte cell adhesion molecule (ALCAM) in samples collected after treatment for cHL.
Conclusions: This study identified three possible biomarkers for cardiac damage in patients treated for cHL. We believe that optimizing treatment based on prognostic factors in this population has the potential to reduce future morbidity and mortality.
Johan Mattsson Ulfstedt, Eva Freyhult, Christina Christersson, Charlott Mörth, Masood Kamali-Moghaddam, Anna Eriksson, Gunilla Enblad, Daniel Molin