In a recent study reported by Marlow et al in The Journal of Pediatrics, researchers assessed the risk of leukemia in children with Down syndrome. Their findings pointed to stronger-than-expected associations between Down syndrome and acute myeloid leukemia (AML).

Down syndrome is one of the most common genetic conditions in the United States and Canada. According to the U.S. Centers for Disease Control and Prevention, about 6,000 babies with Down syndrome are born in the United States each year.

Children with Down syndrome have a substantially increased risk of multiple health conditions compared to the general population. They have a particularly elevated risk (estimated 150-fold) of developing AML before age 5.

Study Methods

The researchers examined medical data of more than 3.9 million children born from 1996 to 2016 in seven U.S. health-care systems or in Ontario, Canada. The data included the children's health information from birth to cancer diagnosis, death, age of 15 years, disenrollment, or December 30, 2016.

"One main strength of this study is its large cohort with more leukemia cases in children with Down syndrome than most previous studies," said first study author Emily Marlow, PhD, a recent graduate from University of California, Davis Department of Public Health Sciences and Graduate Group in Epidemiology. "This allowed more precise risk estimation, especially for rare leukemia types such as AML-7, previously estimated from small case reports."

The study estimated the incidence and hazard ratios of leukemia for children with Down syndrome and other children, adjusting for health system, child's age at diagnosis, birth year, and sex.

Risk of Developing Leukemia

The research team found that 2.8% of children with Down syndrome were diagnosed with leukemia, compared to 0.05% of other children.

Compared to other children, those with Down syndrome had a higher risk of developing AML before age 5 and a higher risk of developing acute lymphoid leukemia (ALL) regardless of their age. In children with Down syndrome, ALL was more common between ages 2 and 4 years, while AML was more common in younger children—the highest incidence during the first year of life. For other children, AML incidence remained very low through age 14 years, whereas ALL incidence peaked at age 3 years and steadily declined until age 8 years.

The study also found that males and Hispanic children were more likely to be diagnosed with Down syndrome and more likely to develop leukemia than their counterparts. White children have a higher incidence rate of ALL and are more likely to have Down syndrome than Black children.

The study authors concluded, “Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.”

Disclosure: For full disclosures of the study authors, visit jpeds.com.