Association of Down syndrome, AML ‘stronger than previously reported’
Down syndrome remained a significant risk factor for pediatric leukemia, especially acute myeloid leukemia, among a large modern cohort of children, according to a retrospective study published in The Journal of Pediatrics.
These associations, particularly that for AML, appeared stronger than previously reported, according to the researchers.
“Parents of children with Down syndrome should talk with their health care providers if their children exhibit any signs of leukemia such as fatigue, pale skin, infections, easy bleeding or bruising, and shortness of breath,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics in the department of public health sciences at UC Davis Health School of Medicine, told Healio.
“Prior research has found that Down syndrome is a strong risk factor for leukemia, but these studies were mostly based on older cohorts,” Miglioretti added, referring to previous studies that used data from children born as early as the 1930s. “We wanted to quantify risk in a large, contemporary cohort.”
The analysis included data of nearly 4 million children born between 1996 and 2016 in seven U.S. health care systems or Ontario, Canada, who researchers followed from birth to cancer diagnosis, death, age 15 years, disenrollment or end of follow-up on Dec. 31, 2016. Of them, 4,401 (54.7% male; 65% aged 5 years or older at end of follow-up) had Down syndrome.
Miglioretti and colleagues used tumor registries to identify cancer diagnoses and then estimated incidence and HRs for leukemia among children with or without Down syndrome, adjusting for health care system, age at diagnosis, birth year and sex. Researchers calculated associations between Down syndrome and leukemia (both overall and by subtype) using the Fine and Gray extension of the Cox proportional hazards model to account for competing risks.
Results showed a greater proportion of children with vs. without Down syndrome were diagnosed with leukemia (2.8% vs. 0.05%).
Researchers noted the cumulative incidence of leukemia varied among children with Down syndrome according to disease subtype. For AML, researchers calculated a cumulative incidence of 1,405 (95% CI, 1,076-1,806) per 100,000 children at age 4 years, which they noted increased sharply from birth to age 2 years and remained unchanged between ages 4 and 14 years.
“We were surprised to find associations between Down syndrome and acute myeloid leukemia that were stronger than previously reported,” Miglioretti said.
Cumulative incidence of acute lymphoblastic leukemia among children with Down syndrome was 1,059 (95% CI, 755-1,451) per 100,000 children at age 4 years and 1,714 (95% CI, 1,264-2,276) per 100,000 children at age 14 years.
Researchers observed greater risks for any leukemia diagnosis associated with Down syndrome among those aged younger than 5 years (HR = 75; 95% CI, 62-91) than those aged 5 years or older (HR = 18; 95% CI, 8-43), with greatest risk observed for megakaryoblastic leukemia, a subtype of AML, among children aged younger than 5 years (HR = 1,500; 95% CI, 555-4,070).
Regardless of age, children with Down syndrome had a greater risk for ALL than other children (age < 5 years: HR = 28; 95% CI, 20-40; age 5 years HR = 21; 95% CI, 12-38).
Determining whether increased exposure to ionizing radiation in childhood also increases leukemia risk among children with Down syndrome should be explored in future research, according to the researchers.
“Given the potential for ionizing radiation to increase leukemia risk in children, other non-ionizing radiation imaging modalities, such as ultrasound and MRI, should be used when possible,” Miglioretti told Healio. “If a higher-dose modality, such as CT, is warranted, the dose should be kept as low as possible for clinical diagnosis.”
For more information:
Diana L. Miglioretti, PhD, can be reached at Department of Public Health Sciences, UC David School of Medicine, One Shields Ave., Med Sci 1C, Room 106, Davis, CA 95616; email: dmiglioretti@ucdavis.edu.
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