Relative Risk of Cardiovascular Disease after Treatment for Aggressive Non-Hodgkin's Lymphoma.

Abstract

Cardiovascular complications after therapy for Hodgkin lymphoma have been related to radiotherapy on the mediastinum, but have only incidentally been studied in NHL. As cardiovascular disease occurs commonly in the normal population, it is important to realize that risk factors as age, hypertension and life-style (diet and smoking) may be more outspoken in patients with NHL, who are generally older than patients with Hodgkin lymphoma. Moreover, although most patients with aggressive NHL will initially receive only chemotherapy, many will be treated with more than one therapy modality, incorporating stem cell transplantation or radiotherapy, because of early failure or relapses. Therefore, risk estimation of cardiovascular disease in NHL patients requires comparison to population-based rates. Here, we evaluated whether patients with aggressive NHL treated in 4 EORTC trials between 1980–1999 have an increased excess cardiovascular risk, compared to Dutch population rates. Relative risks (RR) and absolute excessive risks (AER per 1000 person-years) of cardiovascular disease were determined in 476 (Dutch and Belgian) patients and compared to incidence rates from the Continuous Morbidity Registry Nijmegen. Analyses were restricted to those patients treated with at least 6 cycles of doxorubicin-based chemotherapy and with a minimal follow-up time of 0.5 years. Only serious late events requiring daily medication and/or clinical interventions were recorded. Cumulative incidences of cardiovascular disease were estimated in the competing risk model by Gray with death by any cause as competing event. The overall cumulative incidence of cardiovascular disease was 12% at 5 and 22% at 10 years. At a median follow-up of 8.4 years, 66 cases of chronic heart failure (RR 5.4, 95% CI 4.1–6.9, AER 20.8), 17 myocardial infarctions (RR 1.2; 0.8–1.8, AER 0.8), 12 strokes (RR 1.8; 1.1–2.4, AER 1.5) and 9 other large vessel occlusions were registered. The large vascular events including strokes occurred in 16/21 patients after radiotherapy given in the same area. Pre-existent hypertension, NHL at young age (<55 years) and (any) salvage treatment increased risk of cardiovascular disease. Excess risk for myocardial infarction or stroke after radiotherapy on respectively the mediastinum or neck depended on cumulative radiation dose and was only seen after more than 40 Gy. Excess risk for chronic heart failure was registerd in both non-irradiated (RR 4.4) and irradiated patients, with an extremely high RR of 32 (13.7–57.0) if >40 Gy had been given. In conclusion, NHL patients treated with doxorubicin-based chemotherapy, especially those who are young, have hypertension, or received salvage treatment or radiotherapy above 40 Gy, are at high risk of cardiovascular disease and need lifelong monitoring in this regard.