Background Hodgkin Lymphoma treatment is associated with high risk of treatment-related morbidity, including second cancers and cardiovascular diseases. However, only few studies examined long-term excess mortality.
Methods We studied cause-specific mortality in a multicenter cohort comprising 3,575 5-year HL-survivors, diagnosed before age 51 and treated between 1965 and 1995. Follow-up was complete until at least January 2010 for 96% of the patients. For 93% of deaths, the cause was known. Mortality after HL was compared with mortality in the general population by calculating standardized mortality ratios (SMRs) and absolute excess mortality (AEM), expressed per 10,000 person-years. Treatment-specific SMRs were compared by Poisson regression.
Results After a median follow-up of 21.6 years since HL treatment 1,328 patients had died (19.5% from HL, 32.5% from solid tumors, 15.5% from cardiac diseases, 7.0% from NHL/leukemia). The SMR for causes other than Hodgkin Lymphoma was 8.2-fold that of the general population. The cohort experienced 149.2 excess deaths per 10,000 patients per year. The SMR and AEM for causes of death other than Hodgkin Lymphoma increased throughout follow-up: after ≥35 years the SMR was 19.2, translating to 505.9 excess deaths per 10,000 patients per year. Solid tumors accounted for the largest part of the excess mortality (overall SMR 5.6, AEM 56.1). While the SMR for solid tumors remained stable, the SMR for cardiac diseases (overall SMR 9.8, AEM 29.4) increased during follow-up (SMR at ≥35 years 28.8, p-trend<0.001)). Adjusted for sex, age and follow-up time, risk of death from cardiac diseases was increased for patients treated with supradiaphragmatic radiotherapy (Relative Risk (RR) 4.8, p<0.001) or anthracyclines (RR 1.5, p=0.044). The SMR for infectious causes (2.9% of all deaths, including deaths due to influenza/pneumonia) was 6.5-fold increased. Both splenectomy (RR 2.1, p=0.041) and spleen radiotherapy (RR 3.2, p=0.001) were associated with increased risk of death due to infectious causes compared to patients not receiving such treatment.
Conclusions Even 35 years after treatment, HL Hodgkin Lymphoma patients experienced elevated SMRs and AEMs from solid tumors and cardiac diseases. Both splenectomy and spleen radiotherapy increased mortality due to infections.