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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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NEOPLASIA

Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin lymphoma

Elizabeth C. Moser, Evert M. Noordijk, Flora E. van Leeuwen, Saskia le Cessie, Joke W. Baars, José Thomas, Patrice Carde, Jacobus H. Meerwaldt, Martine van Glabbeke, and Hanneke C. Kluin-Nelemans

From the European Organization for Research on Treatment of Cancer (EORTC) Data Center, Brussels, Belgium; the Department of Radiotherapy, Leiden University Medical Center, The Netherlands; the Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam, The Netherlands; the Department of Medical Statistics, Leiden University Medical Center, The Netherlands; the Department of Medical Oncology, Antoni van Leeuwenhoek ziekenhuis, Amsterdam, The Netherlands; the Department of Oncology, U.Z. Gasthuisberg, Leuven, Belgium; the Department of Hematology, Institute Gustave Roussy, Villejuif, France; the Department of Radiotherapy, Medical Spectrum Twente, Enschede, The Netherlands; and the Department of Hematology, University Medical Center, University of Groningen, The Netherlands.

Cardiovascular disease frequently occurs after lymphoma therapy, but it 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 European Organization for Research on Treatment of Cancer (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 of 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 person-years, whereas risk of coronary artery disease matched the general population (SIR, 1.2; 95% CI, 0.8-1.8; AER, 8 per 10 000 person-years). Risk of stroke was raised (SIR, 1.8; 95% CI, 1.1-2.4; AER, 15 per 10 000 person-years), especially after additional radiotherapy (> 40 Gy). Preexisting hypertension, NHL at young age, and salvage treatment increased risk of all cardiovascular events; the effect 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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