Childhood Down Syndrome Remains Strong Risk Factor for Leukemia, Specifically Associations With AML

Matthew Fowler

A retrospective study evaluating over 3.9 million children found that Down syndrome was a strong risk factor for the development of childhood leukemia and has a stronger association with acute myeloid leukemia than previously recorded.

A retrospective study determined that Down syndrome continues to be a risk factor for childhood leukemia, with acute myeloid leukemia (AML) associations found to be stronger than previously understood, according to data published in The Journal of Pediatrics.

“In a large, contemporary cohort of 3.9 million children, we found that the leukemia risks were greatly elevated in children with Down syndrome, and for some leukemia subtypes the risks were greater than previously reported,” wrote the investigators.

This research included over 3.9 million children born between 1996 and 2016 in 7 United States health care systems or Ontario, Canada. Of that cohort, 124 of 4401 children with Down syndrome and 1941 of 3,900,998 other children were diagnosed with leukemia.

Specifically, the cumulative incidence of AML for this cohort was 1405 of 100,000 (95% CI, 1076-1806) at age 4 and remained unchanged at age 14, with the cumulative incidence of acute lymphoblastic leukemia (ALL) for children with Down syndrome observed in 1059 of 100,000 children (95% CI, 755-1451) at age 4 and 1714 of 100,000 (95% CI, 1264-2276) at age 14 years.

For children with Down syndrome in this population, this group was at a greater risk of AML before age 5 than the other children in this population (95% CI, 281-566). More, regardless of age, the analysis found that children with Down syndrome were also at a greater risk of ALL than other children included in the research (<5 years: 95% CI, 20-40; ³5 years: 95% CI, 12-38).

“We found a stronger association between Down syndrome and AML risk than previously reported,” wrote the investigators. “The effect of Down syndrome on leukemia risk was largest for AML-M7 and for AML diagnoses in children <5 years of age. Associations between Down syndrome and ALL were consistent with previous reports.”

A limitation of the research includes the different identifying definitions for children with Down syndrome between the United States systems and Ontario, Canada. The diagnoses codes for Down syndrome in Ontario were only available from hospital visits, while the codes in the United States were required from “at least three unique days unless chart reviewed.”

More, children with leukemia were more likely to be hospitalized, thus resulting in the potential that Down syndrome diagnoses were more often coded in these patients than patients without leukemia.

Despite these limitations, the results for age-specific ALL incidence for children under the age of 15 without Down syndrome found here were consistent with estimates for the general population.

“Further research is warranted to investigate why our study’s AML rates for children with Down syndrome were much greater than previous reports and whether they are related to identifiable exposures such as ionizing radiation from medical imaging,” wrote the investigators.

Reference:

Marlow EC, Ducore J, Kwan ML, et al. Leukemia Risk in a Cohort of 3.9 Million Children with and without Down Syndrome. J Pediatr. March6, 2021. doi:10.1016/j.jpeds.2021.03.001