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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2912-2919.
Prepublished online as a Blood First Edition Paper on December 8, 2005; DOI 10.1182/blood-2005-08-3392.
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Submitted August 22, 2005
Accepted November 15, 2005
Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin's lymphoma
Elizabeth C Moser*, Evert M Noordijk, Flora E van Leeuwen, Saskia le Cessie, Joke W Baars, Jose Thomas, Patrice Carde, Jacobus H Meerwaldt, Martine van Glabbeke, and Hanneke C Kluin-Nelemans
EORTC Data Center, Brussels, Belgium; Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands
Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Oncology, Antoni van Leeuwenhoek ziekenhuis, Amsterdam, The Netherlands
Department of Oncology, U.Z. Gasthuisberg, Leuven, Belgium
Department of Hematology, Institute Gustave Roussy, Villejuif, France
Department of Radiotherapy, Medical Spectrum Twente, Enschede, The Netherlands
EORTC Data Center, Brussels, Belgium
Department of Hematology, University Medical Center, University of Groningen, Groningen, The Netherlands
* Corresponding author; email: e.c.moser{at}lumc.nl.
Cardiovascular disease frequently occurs after lymphoma therapy, but is common in the general population too. Therefore, risk estimation requires comparison to population-based rates. We calculated risk by standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years based on general population rates (Continuous Morbidity Registry Nijmegen) in 476 (Dutch and Belgian) patients with aggressive non Hodgkin lymphoma (NHL) treated with at least 6 cycles of doxorubicin-based chemotherapy in 4 EORTC trials (1980-1999). Cumulative incidence of cardiovascular disease, estimated in a competing risk model was 12% at 5 years and 22% at 10 years (median follow-up 8.4 years). Risk for chronic heart failure appeared markedly increased (SIR 5.4, 95% CI 4.1-6.9) with an AER of 208 excess cases per 10,000 py, whereas risk of coronary artery disease matched the general population (SIR 1.2, 95% CI; 0.8-1.8, AER 8/10,000 py). Risk of stroke was raised (SIR 1.8, 95% CI; 1.1-2.4, AER 15/10,000 py), especially after additional radiotherapy ( >40 Gy). Pre-existent hypertension, NHL at young age and salvage treatment increased risk for all cardiovascular events; the impact of radiotherapy was dose-dependent.
In conclusion, patients are at long-term high risk of chronic heart failure after NHL treatment and need therefore life-long monitoring. In contrast, risk of coronary artery disease appeared more age-dependent than treatment related.
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