BACKGROUND Hodgkin lymphoma survivors demonstrated increased risk of secondary primary malignancies (SPMs), but comprehensive analysis of the risk and outcome of SPMs in classical Hodgkin lymphoma (cHL) patients has not yet been reported. METHODS Patients with classical Hodgkin Lymphoma from 1975 to 2017 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Standardized incidence ratios (SIRs) were calculated for the risk of solid and hematologic SPMs in cHL patients compared to the general population. The outcome of cHL patients developing SPMs were assessed by performing survival, competing risks regression and cox proportional regression analyses. RESULTS In a follow-up of 26,493 cHL survivors for 365,156 person years, 3,866 (14.59%) secondary cancers were identified, with an SIR of 2.09 (95% CI: 2.02 - 2.15). The increased risk was still notable after follow-up of 10 years or more, and the risk is more pronounced for patients with female gender, younger age, advanced stage, chemotherapy and radiation therapy. The overall survival is worse for cHL patients with SPMs after 5 years of follow-up (P < 0.0001). The main cause of death for cHL patients with SPMs is not cHL but other causes including SPMs. Multivariate Cox regression analysis confirmed SPMs as an independently adverse prognostic factor for cHL survivors (hazard ratio, 1.08; 95% CI, 1.03-1.14, P = 0.002). CONCLUSIONS There is a significantly increased risk of developing SPMs for cHL survivors. The overall survival is worse for cHL patients and SPMs is an independent prognostic factor for cHL.

The authors have declared no competing interest.

This work was supported by the National Science Foundation of China, No. 82070174.

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