Irish Journal of Medical Science (1971 -)

, Volume 184, Issue 4, pp 877–882 | Cite as

Child and adolescent Down syndrome-associated leukaemia: the Irish experience

  • C. O’Rafferty
  • J. Kelly
  • L. Storey
  • C. Ryan
  • A. O’Marcaigh
  • O. Smith
Original Article



Down syndrome (DS), the most common syndromic chromosomal abnormality is associated with a unique susceptibility to develop both acute myeloid (ML) and lymphoblastic leukaemia (ALL). These leukaemias differ from the non-DS-related types of leukaemia and are thought to be distinct biological entities.


To perform a retrospective review of our experience of treating DS-related leukaemia at Our Lady’s Children’s Hospital.


Data were extracted from a database established in 2000 to prospectively gather data on DS-associated leukaemias and their outcomes following polychemotherapy. Kaplan–Meier survival curves were constructed.


Nineteen patients with DS-ML were treated and 19 with DS-ALL. Sixteen (84 %) patients with DS-ML are alive and in complete remission with a median follow-up of 7 years. All deaths in this cohort were due to treatment-related mortality (TRM). Of the DS-ALL patients, 12 (63 %) remain alive with a median follow-up of 3.6 years. TRM accounted for five of the six deaths. One death was due to leukaemic relapse.


High cure rates are seen in DS-ML using contemporary polychemotherapy protocols, however, there is significant TRM in this cohort. DS-ALL does not have the same high cure rate as non-DS-ALL (>90 %) and again this is mainly due to an excess of TRM.


Down syndrome Acute lymphoblastic leukaemia Down syndrome myeloid leukaemia Megakaryoblastic leukaemia Treatment-related mortality Prognosis 


Conflict of interest



  1. 1.
    Weijerman ME, de Winter JP (2010) Clinical practice. The care of children with Down syndrome. Eur J Pediatr 169(12):1445–1452PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Bruwier A, Chantrain CF (2012) Hematological disorders and leukemia in children with Down syndrome. Eur J Pediatr 171(9):1301–1307CrossRefPubMedGoogle Scholar
  3. 3.
    Hasle H, Clemmensen IH, Mikkelsen M (2000) Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet 355(9199):165–169CrossRefPubMedGoogle Scholar
  4. 4.
    Xavier AC, Ge Y, Taub J (2010) Unique clinical and biological features of leukemia in Down syndrome children. Expert Rev Hematol 3(2):175–186CrossRefPubMedGoogle Scholar
  5. 5.
    Khan I, Malinge S, Crispino J (2011) Myeloid leukemia in Down syndrome. Crit Rev Oncog 16(1–2):25–36PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Massey GV, Zipursky A, Chang MN, Doyle JJ, Nasim S, Taub JW et al (2006) A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children’s Oncology Group (COG) study POG-9481. Blood 107(12):4606–4613CrossRefPubMedGoogle Scholar
  7. 7.
    Dordelmann M, Schrappe M, Reiter A, Zimmermann M, Graf N, Schott G et al (1998) Down’s syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Munster Group. Leukemia 12(5):645–651CrossRefPubMedGoogle Scholar
  8. 8.
    Whitlock JA, Sather HN, Gaynon P, Robison LL, Wells RJ, Trigg M et al (2005) Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood 106(13):4043–4049CrossRefPubMedGoogle Scholar
  9. 9.
    Bassal M, La MK, Whitlock JA, Sather HN, Heerema NA, Gaynon PS et al (2005) Lymphoblast biology and outcome among children with Down syndrome and ALL treated on CCG-1952. Pediatr Blood Cancer 44(1):21–28CrossRefPubMedGoogle Scholar
  10. 10.
    Chessells JM, Harrison G, Richards SM, Bailey CC, Hill FG, Gibson BE et al (2001) Down’s syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment. Arch Dis Child 85(4):321–325PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, van den Heuvel-Eibrink MM et al (2013) Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood 123(1):70–77CrossRefPubMedGoogle Scholar
  12. 12.
    Izraeli S, Vora A, Zwaan CM, Whitlock J (2013) How I treat ALL in Down’s syndrome: pathobiology and management. Blood 123(1):35–40CrossRefPubMedGoogle Scholar
  13. 13.
    Patrick K, Wade R, Goulden N, Rowntree C, Hough R, Moorman AV et al (2014) Outcome of Down Syndrome associated Acute Lymphoblastic Leukaemia treated on a contemporary protocol. Br J Haematol 165(4):552–555CrossRefPubMedGoogle Scholar
  14. 14.
    Creutzig U, Reinhardt D, Diekamp S, Dworzak M, Stary J, Zimmermann M (2005) AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity. Leukemia 19(8):1355–1360CrossRefPubMedGoogle Scholar
  15. 15.
    Rao A, Hills RK, Stiller C, Gibson BE, de Graaf SS, Hann IM et al (2006) Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials. Br J Haematol 132(5):576–583CrossRefPubMedGoogle Scholar
  16. 16.
    Ram G, Chinen J (2011) Infections and immunodeficiency in Down syndrome. Clin Exp Immunol 164(1):9–16PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Buitenkamp TD, Mathot RA, de Haas V, Pieters R, Zwaan CM (2010) Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia. Haematologica 95(7):1106–1113PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Taub JW, Matherly LH, Stout ML, Buck SA, Gurney JG, Ravindranath Y (1996) Enhanced metabolism of 1-beta-D-arabinofuranosylcytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syndrome children with acute myeloid leukemia. Blood 87(8):3395–3403PubMedGoogle Scholar
  19. 19.
    Maloney KW, Carroll WL, Carroll AJ, Devidas M, Borowitz MJ, Martin PL et al (2010) Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children’s Oncology Group. Blood 116(7):1045–1050PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J et al (2009) Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet 41(11):1243–1246PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Maude SL, Tasian SK, Vincent T, Hall JW, Sheen C, Roberts KG et al (2012) Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 120(17):3510–3518PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Royal Academy of Medicine in Ireland 2014

Authors and Affiliations

  • C. O’Rafferty
    • 1
  • J. Kelly
    • 2
  • L. Storey
    • 1
  • C. Ryan
    • 3
  • A. O’Marcaigh
    • 1
  • O. Smith
    • 1
    • 4
  1. 1.Department of HaematologyOur Lady’s Children’s HospitalDublin 12Ireland
  2. 2.National Centre for Medical GeneticsOur Lady’s Children’s HospitalDublin 12Ireland
  3. 3.Department of HaematologyMercy HospitalCorkIreland
  4. 4.Trinity CollegeDublin 2Ireland

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