Leukemia Risk in a Cohort of 3.9 Million Children with and without Down Syndrome

Emily C. Marlow, Jonathan M Ducore, Marilyn L. Kwan, Stephanie Y. Cheng, Erin J.A. Bowles, Robert T. Greenlee, Jason D. Pole, Alanna Kulchak Rahm, Natasha K. Stout, Sheila Weinmann, Rebecca Smith-Bindman, Diana L. Miglioretti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalJournal of Pediatrics
DOIs
StateAccepted/In press - 2021

Keywords

  • acute lymphoid leukemia
  • acute myeloid leukemia
  • childhood leukemia risk
  • Down syndrome
  • retrospective cohort

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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