Purpose: Although epilepsy has been reported in survivors of childhood cancer outside the central nervous system (CNS), little evidence exists on risk factors for this late complication. Our study aimed to identify risk factors of late-onset epilepsy.

Methods: A case-cohort study was conducted within 5-year survivors of non-CNS childhood cancer from the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study, including 81 survivors diagnosed with late-onset epilepsy and a sub-cohort of 231 randomly selected survivors. Detailed treatment information was obtained from medical records. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated to assess the association between treatment-related factors and epilepsy.

Results: Survivors of acute lymphoblastic leukemia (ALL) and other types of leukemia exhibited significantly higher IRRs for epilepsy compared to survivors of solid tumors (ALL: 4.4, 95% CI 2.2-8.5; other leukemia: 14.1, 95% CI 3.4-57.9). Relapse was associated with an increased IRR of epilepsy (3.5, 95% CI 1.5-8.6). Specifically, survivors of relapsed leukemia demonstrated a high IRR for epilepsy (11.4, 95% CI 3.5 - 37.3) compared to non-relapsed survivors. No association was found between epilepsy and bone marrow transplantation, radiotherapy, total body irradiation, or treatment with specific chemotherapeutic agents. Finally, survivors diagnosed after 1990 had a decreased IRR of epilepsy (0.4, 95% CI 0.2 - 0.8) compared to survivors diagnosed in 1970 - 1979.

Conclusion: Relapsed leukemia survivors were at increased risk for late-onset epilepsy.

Implications for cancer survivors: Awareness of the risk of epilepsy in leukemia survivors is important, especially among those with relapse, to detect and manage epilepsy early and mitigate its impact on quality of life.