What question did this study set out to answer?

The study aims to explore the relationship between plasma proteomics and cardiotoxicity in patients with Hodgkin lymphoma treated with chemotherapy and radiotherapy.

January 10, 2026Cardio-Oncology0 citationsOpen Access

Exploratory study linking plasma proteomics to cardiotoxicity in Hodgkin lymphoma

JUJohan Mattsson UlfstedtUppsala University RRRagnhild RisebroUppsala University EFEva FreyhultUppsala University

Key Result

In cHL patients treated with doxorubicin, post-treatment levels of CYR61, GPNMB, and ALCAM were significantly associated with heart failure and ischemic heart disease.

Key Points

The study aims to explore the relationship between plasma proteomics and cardiotoxicity in patients with Hodgkin lymphoma treated with chemotherapy and radiotherapy.
Analyzed 182 proteins in plasma samples from 56 Hodgkin lymphoma patients and 60 controls.
Used Olink multiplex protein panels Oncology II and Cardiovascular III for protein analysis.
Supplemented analysis with NTpro-BNP, troponin I, and C-reactive protein measurements.
Collected blood samples prospectively before, during, and after treatment.
Identified significant associations between heart failure and ischemic heart disease and specific protein biomarkers: CYR61, GPNMB, and ALCAM.
Revealed three novel biomarkers linked to cardiovascular disease in post-treatment Hodgkin lymphoma patients.
Potential for biomarkers to enhance risk prediction suggests a need for closer monitoring of high-risk patients.

Structured PICO

Do plasma protein biomarkers predict the development of cardiovascular disease in patients treated with doxorubicin for classical Hodgkin lymphoma?

Population

56 patients with primary (n=54) or recurrent (n=2) classical Hodgkin lymphoma (cHL), mean age 46.2 years, 62.5% male, from a single center in Sweden, and 60 healthy controls without known malignancies.

Intervention

Doxorubicin-based chemotherapy (mean dose 234 mg/m2) with or without radiotherapy (11 patients received mediastinal radiation).

Comparator

Patients within the cHL cohort who did not develop cardiovascular disease (for biomarker analysis), and 60 healthy controls without known malignancies (for baseline comparisons).

Outcome

Compound endpoint of cardiovascular disease (including heart failure, coronary artery disease, coronary artery intervention, cardiac arrest, atrial fibrillation, pacemaker, clinically relevant valvular disease, or vascular disease).composite

Plasma biomarkers CYR61, GPNMB, and ALCAM are elevated post-treatment in classical Hodgkin lymphoma patients who subsequently develop cardiovascular disease, suggesting potential utility for early cardiotoxicity risk stratification.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Original Research. Background Cardiovascular toxicity is a well-known complication of 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 relapse of lymphoma. This highlights the need for strategies to minimize toxicity.Our aim was to characterize the prevalence of cardiovascular diseases (CVDs) 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 preexisting or emerging CVD posttreatment. Methods We analyzed 182 different proteins in plasma samples from 56 cHL patients and 60 controls using Olink multiplex protein panels Oncology II and Cardiovascular III. The analysis was supplemented with separate analyses of N-terminal pro-brain natriuretic peptide (NTpro-BNP), troponin I and C-reactive protein (CRP). The patient samples were prospectively collected prior to, during and after treatment. Results Our analysis revealed 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 exploratory study identified three new biomarkers reflecting different biological processes associated with CVD in patients treated for cHL. Adding biomarkers to risk prediction in this population has the potential to identify patients with a high risk of cardiovascular events who need focused follow-up.

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