To assess leukemia risks among children with Down syndrome in a large, contemporary cohort.
Retrospective cohort study including 3,905,399 children born 1996-2016 in seven U.S. healthcare systems or Ontario, Canada and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using ICD9/10 diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child's age at diagnosis, birth year, and sex.
Leukemia was diagnosed in 124 of 4,401 children with Down syndrome and 1,941 of 3,900,998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1,405/100,000 [95% confidence interval (CI)=1076-1,806] at age 4 and unchanged at age 14. The cumulative incidence of acute lymphoid leukemia (ALL) in children with Down syndrome was 1,059/100,000 (95%CI=755-1,451) at age 4 and 1,714/100,000 (95%CI=1,264-2,276) at age 14. Children with Down syndrome had higher risk of AML before age 5 than other children (HR=399, 95%CI=281-566). Largest HRs were for megakaryoblastic leukemia before age 5 (HR=1,500, 95%CI=555-4,070). Children with Down syndrome had a higher risk of ALL than other children regardless of age (<5 years: HR=28, 95%CI=20-40, ≥5 years HR=21, 95%CI=12-38).
Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.