Dysfunctional endothelial progenitor cells in patients with Hodgkin’s lymphoma in complete remission

Background: Patients with a history of Hodgkin's lymphoma (HL) are at increased long-term risk of cardiovascular morbidity and mortality. Studies report an association between the pathophysiology of coronary artery disease (CAD) and levels of circulating endothelial progenitor cells (EPC), which play an essential role in vascular injury repair. The aim of the present study was to investigate the potential involvement of abnormal EPC level or function in the CAD risk of survivors of HL in remission. Methods: EPCs were isolated from peripheral blood samples drawn from 4 groups of patients aged 20-50 years with no history of CAD: 17 patients with HL who had been in complete remission for at least 2 years, four newly diagnosed patients with HL before treatment, 28 patients with diabetes all attending a tertiary medical center, and 16 healthy individuals. Levels of EPC surface markers were measured by flow cytometry, and EPC function was evaluated by the number of colony-forming units (CFUs) and MTT assay. Results: Levels of circulating CD34(+)/VEGFR2(+) and CD133(+)/VEGFR2(+) were significantly higher in the newly diagnosed untreated patients with HL compared to the patients with HL in remission (P = 0.03 and P = 0.005, respectively), in the patients in remission compared to the patients with diabetes (P = 0.011 and P < 0.001, respectively), and in the patients in remission compared to the healthy individuals (P = 0.08 and P = 0.003, respectively). The analysis of cell viability and the number of colony-forming units in the patients with HL in remission yielded significant differences from the healthy group (P = 0.005 and P < 0.001, respectively) but not from either the newly diagnosed patients with HL or the diabetic patients. Conclusions: These results suggest that patients in complete remission of HL for at least 2 years have an abnormal EPC profile characterized by high circulating levels but attenuated function.