Cancer Res Treat.  2022 Apr;54(2):572-578. 10.4143/crt.2021.368.

Epidemiology of Acute Leukemia among Children with Down Syndrome in Korea

• Choi YB
• Yoo KH

• KMID: 2528226
• DOI: http://doi.org/10.4143/crt.2021.368

Abstract

Purpose
Children with Down syndrome (DS) show a higher risk of acute leukemia than those without DS. In this study, we investigated the nationwide incidence of acute leukemia among children with DS and compared their epidemiologic characteristics with those of children with acute leukemia but without DS.
Materials and Methods
Using the National Health Insurance Service database, we selected patients with acute leukemia aged 0–19 years at diagnosis between 2007 and 2016.
Results
Among the 4,697 children with acute leukemia, 54 (1.1%) had DS. The median incidence rate of leukemia with DS by year was 1.3% (range, 0.2%–2.0%). Sixteen patients with acute lymphoblastic leukemia (ALL; 29.6%) and 36 with acute myeloid leukemia (AML; 66.7%) had DS. The DS group showed younger age at diagnosis than the non-DS group, and diagnosis of AML was more frequent in the DS group than in the non-DS group (3 years vs. 9 years, p<0.001; 66.7% vs. 32.4%, P<0.001, respectively). The 5-year overall survival was comparable between the DS and non-DS groups (88.0% vs. 81.9%, p=0.375). Among all the Koreans born between 2007 and 2008, the incidences of acute leukemia, ALL, and AML were 49.25, 20.75, and 163.38 times higher, respectively, in the DS group than in the non-DS group.
Conclusion
Our findings support the fact that the incidence of acute leukemia is higher among patients with DS than among those without DS in Korea. However, the DS and non-DS groups in this study had a comparable overall survival rate.

Keyword

Acute leukemia; Precursor cell lymphoblastic leukemia-lymphoma; Acute myeloid leukemia; Childhood; Down syndrome; Lymphoma

Figure

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  Fig. 1 Age-specific distribution of patients diagnosed with acute leukemia from 2007 to 2016. (A) Acute leukemia with Down syndrome (DS). (B) Acute leukemia without DS. Among patients younger than 5 years of age, 63% of the patients in the DS group had acute myeloid leukemia (AML), and 69% of the patients in the non-DS group had acute lymphoblastic leukemia (ALL).

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  Fig. 2 Overall survival rates of patients with acute leukemia with or without Down syndrome (DS) from 2007 to 2016. (A) Acute leukemia. (B) Acute lymphoblastic leukemia (ALL). (C) Acute myeloid leukemia (AML). There was no statistical difference between the overall survival rates of patients with acute leukemia, ALL, and AML in the DS and non-DS groups.

Reference

References

1. Tabares-Seisdedos R, Dumont N, Baudot A, Valderas JM, Climent J, Valencia A, et al. No paradox, no progress: inverse cancer comorbidity in people with other complex diseases. Lancet Oncol. 2011; 12:604–8.

2. Krivit W, Good RA. Simultaneous occurrence of mongolism and leukemia: report of a nationwide survey. AMA J Dis Child. 1957; 94:289–93.

3. Creutzig U, Ritter J, Vormoor J, Ludwig WD, Niemeyer C, Reinisch I, et al. Myelodysplasia and acute myelogenous leukemia in Down’s syndrome: a report of 40 children of the AML-BFM Study Group. Leukemia. 1996; 10:1677–86.

4. Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB, et al. Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children’s Cancer Group Studies 2861 and 2891. Blood. 1998; 91:608–15.

5. Kojima S, Sako M, Kato K, Hosoi G, Sato T, Ohara A, et al. An effective chemotherapeutic regimen for acute myeloid leukemia and myelodysplastic syndrome in children with Down’s syndrome. Leukemia. 2000; 14:786–91.

6. Lange B. The management of neoplastic disorders of haematopoiesis in children with Down’s syndrome. Br J Haematol. 2000; 110:512–24.

7. Creutzig U, Reinhardt D, Diekamp S, Dworzak M, Stary J, Zimmermann M. AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity. Leukemia. 2005; 19:1355–60.

8. Fong CT, Brodeur GM. Down’s syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis. Cancer Genet Cytogenet. 1987; 28:55–76.

9. Hitzler JK, Zipursky A. Origins of leukaemia in children with Down syndrome. Nat Rev Cancer. 2005; 5:11–20.

10. Ross JA, Spector LG, Robison LL, Olshan AF. Epidemiology of leukemia in children with Down syndrome. Pediatr Blood Cancer. 2005; 44:8–12.

11. James R, Lightfoot T, Simpson J, Moorman AV, Roman E, Kinsey S, et al. Acute leukemia in children with Down’s syndrome: the importance of population based study. Haematologica. 2008; 93:1262–3.

12. Zeller B, Gustafsson G, Forestier E, Abrahamsson J, Clausen N, Heldrup J, et al. Acute leukaemia in children with Down syndrome: a population-based Nordic study. Br J Haematol. 2005; 128:797–804.

13. Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, van den Heuvel-Eibrink MM, et al. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood. 2014; 123:70–7.

14. Whitlock JA, Sather HN, Gaynon P, Robison LL, Wells RJ, Trigg M, et al. Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood. 2005; 106:4043–9.

15. Song SO, Jung CH, Song YD, Park CY, Kwon HS, Cha BS, et al. Background and data configuration process of a nationwide population-based study using the korean national health insurance system. Diabetes Metab J. 2014; 38:395–403.

16. Kim HS, Lyoo CH, Lee PH, Kim SJ, Park MY, Ma HI, et al. Current status of Huntington’s disease in Korea: a nationwide survey and national registry analysis. J Mov Disord. 2015; 8:14–20.

17. Xavier AC, Taub JW. Acute leukemia in children with Down syndrome. Haematologica. 2010; 95:1043–5.

18. Okuda T, Nishimura M, Nakao M, Fujita Y. RUNX1/AML1: a central player in hematopoiesis. Int J Hematol. 2001; 74:252–7.

19. Watanabe K. Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome. Pediatr Int. 2019; 61:222–9.

20. Mejia-Arangure JM, Fajardo-Gutierrez A, Flores-Aguilar H, Martinez-Garcia MC, Salamanca-Gomez F, Palma-Padilla V, et al. Environmental factors contributing to the development of childhood leukemia in children with Down’s syndrome. Leukemia. 2003; 17:1905–7.

21. Cho WK, Lee NY, Han K, Suh BK, Park YG. The population prevalence, associations of congenital heart defect and mortality risk for Down’s syndrome in South Korea based on National Health Insurance Service (NHIS) data. Clin Epidemiol. 2020; 12:519–25.

22. Alexander M, Ding Y, Foskett N, Petri H, Wandel C, Khwaja O. Population prevalence of Down’s syndrome in the United Kingdom. J Intellect Disabil Res. 2016; 60:874–8.

23. Zwaan CM, Kaspers GJ, Pieters R, Hahlen K, Janka-Schaub GE, van Zantwijk CH, et al. Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood. 2002; 99:245–51.

24. Taub JW, Ge Y. Down syndrome, drug metabolism and chromosome 21. Pediatr Blood Cancer. 2005; 44:33–9.

25. Frost BM, Gustafsson G, Larsson R, Nygren P, Lonnerholm G. Cellular cytotoxic drug sensitivity in children with acute leukemia and Down’s syndrome: an explanation to differences in clinical outcome? Leukemia. 2000; 14:943–4.

26. Pui CH, Raimondi SC, Borowitz MJ, Land VJ, Behm FG, Pullen DJ, et al. Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia. J Clin Oncol. 1993; 11:1361–7.

27. Stiller CA, Eatock EM. Patterns of care and survival for children with acute lymphoblastic leukaemia diagnosed between 1980 and 1994. Arch Dis Child. 1999; 81:202–8.

28. Goldsby RE, Stratton KL, Raber S, Ablin A, Strong LC, Oeffinger K, et al. Long-term sequelae in survivors of childhood leukemia with Down syndrome: a childhood cancer survivor study report. Cancer. 2018; 124:617–25.