Abstract

A protective effect of childhood vaccinations on leukemia risk, particularly acute lymphoblastic leukemia (ALL), has been hypothesized, though findings are inconsistent. We used a nationwide cohort of Danish children born 1997-2018 (n = 1,360,230), to examine associations between childhood vaccinations and leukemia (<20 years) using registry data (follow-up: December 31, 2018). Cox proportional hazard models with age as the underlying time estimated hazard ratios (HRs) for leukemia (any, ALL, acute myeloid [AML], and other), comparing vaccinated with unvaccinated children. We also accessed the effect of each additional vaccine dose. During 14,536,819 person-years, 771 children were diagnosed with leukemia (74% ALL, 16% AML, and 10% other). Any vaccination was associated with an increased HR for ALL (HR: 2.76; 95% CI: 0.66-11.58), compared to unvaccinated children, with a change in HR of 1.01 (95% CI: 0.96-1.05) per dose. The corresponding HRs for any leukemia, AML, and other leukemia were 1.04 (95% CI: 0.50-2.17), 0.67 (95% CI: 0.18-2.59) and 0.29 (95% CI: 0.09-0.99), with a change in HR of 0.97 (95% CI: 0.94-1.02), 0.92 (95% CI: 0.84-1.00, p = .062) and 0.88 (95% CI: 0.78-1.00, p = .044) per dose. No significant associations were found for vaccination types, except for the pneumococcal vaccine which was associated with a decreased risk of other leukemia (HR: 0.32; 95% CI: 0.14-0.74). In six-months lag analyses, no significant associations were observed, and decreased risks were attenuated. The results provide no strong evidence that childhood vaccinations reduce leukemia risk. The limited number of unvaccinated cases and wide confidence intervals suggest cautious interpretation of some findings.