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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1878-1886.
Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-07-034405.
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CLINICAL TRIALS AND OBSERVATIONS
Late cardiotoxicity after treatment for Hodgkin lymphoma
Berthe M. P. Aleman1,
Alexandra W. van den Belt-Dusebout2,
Marie L. De Bruin2,
Mars B. van 't Veer3,
Margreet H. A. Baaijens4,
Jan Paul de Boer5,
Augustinus A. M. Hart1,
Willem J. Klokman2,
Marianne A. Kuenen2,
Gabey M. Ouwens2,
Harry Bartelink1, and
Flora E. van Leeuwen2
1 Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands;
2 Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;
3 Department of Hematology, the Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;
4 Department of Radiotherapy, the Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;
5 Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.

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