Clonal hematopoiesis in patients with cancer and its association with risk of thrombosis and prognosis of disease

Abstract

Background

Patients with cancer are at high risk for cardiovascular events, especially venous and arterial thromboembolism (VTE/ATE). Clonal hematopoiesis (CH) has been identified as risk factor for cardiovascular diseases. However, there is limited insight into the impact of CH on thrombosis risk in patients with cancer.

Objectives

The aim of this study was to elucidate the association between CH and cancer-associated VTE and ATE within the framework of the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study.

Methods

Peripheral blood DNA samples collected at study inclusion were screened for CH-associated mutations.

Results

In this study, 967 patients (median age: 61 [interquartile range, IQR: 50-68] years, 49.9% female) were included and followed-up for a median of 24 (IQR: 24-24) months. Of those, 787 (78.3%) had newly diagnosed cancer and 434 (44.9%) had stage IV disease. We identified 52 CH-associated variants in 46 patients (4.8%). Mutations in the genes DNMT3A (48.1%) and TP53 (17.3%) were most commonly found. The presence of CH was not associated with VTE (adjusted subdistribution hazard ratio: 0.68, 95% CI: 0.21-2.19) or ATE risk (adjusted subdistribution hazard ratio: 1.08, 95% CI: 0.15-8.06). Available laboratory parameters and inflammatory and hemostatic biomarkers did not differ according to CH carrier status. Compared with patients without CH, those with CH showed decreased overall survival; however, this was not independent of age.

Conclusion

In our cohort of patients with cancer, the presence of CH was not associated with an increased risk of VTE or ATE. CH had no independent impact on overall survival.