Increased Risk of Leukemia After Radioactive Iodine Therapy in Patients with Thyroid Cancer: A Nationwide, Population-Based Study in Korea

The use of radioactive iodine therapy (RAIT) is increasing in thyroid cancer management. The association between RAIT at high doses and leukemia is well known, but studies of this association in a large population are lacking. This study aims to investigate the association between RAIT and leukemia in the context of current practice.Retrospective analysis of a 542,845 person-year (PY) follow-up of thyroid cancer patients was conducted using the Korean National Health Insurance claims database between January 2008 and December 2013. Patients were categorized according to RAIT dose (no RAI; low dose, ≤30 mCi; moderate dose, 31-100 mCi; high dose, 101-150 mCi; and very high dose, >150 mCi).Among 211,360 thyroid cancer patients, 72 (0.03%) patients developed leukemia during follow-up (median 877 days). The cumulative incidence of leukemia per 10(5) person-year (PY) was 9.8 in the no RAI [95% confidence interval (CI) 6.4-14.4]; 6.1 [CI 1.7-15.7] in the low-dose; 8.6 [CI 3.2-18.7] in the moderate-dose; 29.5 [CI 18.3-45.1] in the high-dose; and 20.9 [CI 11.7-34.4] in the very high-dose groups. The hazard ratios were elevated significantly in the high- and very high-dose groups (HR 3.1 and 2.1, respectively, p<0.001) when compared with the no RAI group.RAIT exceeding 100 mCi was strongly associated with the development of leukemia in a nationwide, population-based study, while lower RAIT doses were not. Considering the favorable survival of patients with thyroid cancer and the potential harm of RAIT, physicians need to consider the pros and cons of RAIT when using this treatment option.