Leukemia Risk in a Cohort of 3.9 Million Children with and without Down Syndrome.
OBJECTIVE
To assess leukemia risks among children with Down syndrome in a large, contemporary cohort.


STUDY DESIGN
Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US 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 International Classification of Diseases, Ninth and Tenth Revisions, 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.


RESULTS
Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5 years: HR 28, 95% CI 20-40, ≥5 years HR 21, 95% CI 12-38).


CONCLUSIONS
Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.
['Marlow|Emily C|EC|', 'Ducore|Jonathan|J|', 'Kwan|Marilyn L|ML|', 'Cheng|Stephanie Y|SY|', 'Bowles|Erin J A|EJA|', 'Greenlee|Robert T|RT|', 'Pole|Jason D|JD|', 'Rahm|Alanna Kulchak|AK|', 'Stout|Natasha K|NK|', 'Weinmann|Sheila|S|', 'Smith-Bindman|Rebecca|R|', 'Miglioretti|Diana L|DL|']
D000293:Adolescent D016022:Case-Control Studies D002648:Child D002675:Child, Preschool D015331:Cohort Studies D004314:Down Syndrome D005260:Female D006801:Humans D015994:Incidence D007223:Infant D007231:Infant, Newborn D007947:Leukemia, Megakaryoblastic, Acute D008297:Male D009864:Ontario D012042:Registries D018570:Risk Assessment D014481:United States
Down syndrome retrospective cohort acute myeloid leukemia acute lymphoid leukemia childhood leukemia risk