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Acute Lymphoblastic Leukemia in Down Syndrome

  • Yasuhiro OkamotoEmail author
Chapter

Abstract

Improvement in the outcomes associated with acute lymphoblastic leukemia (ALL) in Down syndrome (DS-ALL) has been delayed. However, as the clinical characteristics of DS-ALL, including leukemogenesis, are elucidated, strategies for improving the outcomes are being considered and implemented. As host side problems, infectious complications and complication deaths due to immunodeficiency and mucosal disorders are problematic. Close control of infection using prophylactic antibiotics and intravenous immunoglobulin replacement should assist in overcoming these problems. DS-ALL is commonly associated with a poor prognosis for gene abnormality, similar to Ph-like ALL. While selecting appropriate treatment for DS-ALL, minimal residual disease (MRD) is determined to assess the disease status and calculate the risk. DS-ALL is considered as a good indication for immunotherapy, such as inotuzumab ozogamicin, blinatumomab, and chimeric antigen receptor T cell therapy, because of less adverse events than those of anticancer drugs. CRLF2-JAK abnormalities are frequently observed in DS-ALL, and specific therapies targeting them are also being developed. As mentioned above, it is thought that improvements in the treatment of DS-ALL outcomes will lead to similar improvements in other ALL. This review will point out the current and future direction of DS-ALL to clinicians treating DS-ALL and those doing research on DS-ALL.

Keywords

Infectious complication Immunodeficiency Mucosal disorder Ph-like ALL Minimal residual disease CRLF2 Methotrexate 

References

  1. 1.
    Buitenkamp TD, Izraeli S, Zimmermann M, et al. Acute lymphoblastic leukemia in children with down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood. 2014;123(1):70–7.CrossRefGoogle Scholar
  2. 2.
    Hirabayashi S, Hasegawa D, Yamamoto K, et al. Dasatinib and low-intensity chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia in a child with down syndrome. Pediatr Blood Cancer. 2019;66(5):e27612.CrossRefGoogle Scholar
  3. 3.
    Meyr F, Escherich G, Mann G, et al. Outcomes of treatment for relapsed acute lymphoblastic leukaemia in children with down syndrome. Br J Haematol. 2013;162(1):98–106.CrossRefGoogle Scholar
  4. 4.
    Hitzler JK, He W, Doyle J, et al. Outcome of transplantation for acute lymphoblastic leukemia in children with down syndrome. Pediatr Blood Cancer. 2014;61(6):1126–8.CrossRefGoogle Scholar
  5. 5.
    Goto H, Kaneko T, Shioda Y, et al. Hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia and down syndrome. Pediatr Blood Cancer. 2015;62(1):148–52.CrossRefGoogle Scholar
  6. 6.
    Murillo L, Dapena JL, Velasco P, de Heredia CD. Use of inotuzumab-ozogamicin in a child with down syndrome and refractory B-cell precursor acute lymphoblastic leukemia. Pediatr Blood Cancer. 2019;66(4):e27562.CrossRefGoogle Scholar
  7. 7.
    A W, MA K, AC X. Blinatumomab activity in a patient with down syndrome B-precursor acute lymphoblastic leukemia. Pediatr Blood Cancer. 2018;65:2.Google Scholar
  8. 8.
    Rabin K, Izraeli S, Hijiya N, Hitzler J. Need for new thinking: treatment of relapsed leukemia in children with down syndrome. Pediatr Blood Cancer. 2019;66(6):e27644.CrossRefGoogle Scholar
  9. 9.
    Tamaura M, Iwasaki F, Yokosuka T, Fukuda K, Hamonoue S, Goto H. Philadelphia chromosome-positive acute lymphoblastic leukemia and down syndrome. Pediatr Int. 2016;58(8):794–7.CrossRefGoogle Scholar
  10. 10.
    Hanada I, Terui K, Ikeda F, et al. Gene alterations involving the CRLF2-JAK pathway and recurrent gene deletions in down syndrome-associated acute lymphoblastic leukemia in Japan. Genes Chromosomes Cancer. 2014;53(11):902–10.CrossRefGoogle Scholar
  11. 11.
    Murphy BR, Roth M, Kolb EA, Alonzo T, Gerbing R, Wells RJ. Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with down syndrome: A case report and retrospective review of Children's oncology group acute myeloid leukemia trials. Pediatr Blood Cancer. 2019;66:e27700.CrossRefGoogle Scholar
  12. 12.
    Tomizawa D, Endo A, Kajiwara M, et al. Acute lymphoblastic leukemia in patients with down syndrome with a previous history of acute myeloid leukemia. Pediatr Blood Cancer. 2017;64(8):e26411.CrossRefGoogle Scholar
  13. 13.
    Hellebostad M, Carpenter E, Hasle H, Mitchell C, Vyas P. GATA1 mutation analysis demonstrates two distinct primary leukemias in a child with down syndrome; implications for leukemogenesis. J Pediatr Hematol Oncol. 2005;27(7):408–9.CrossRefGoogle Scholar
  14. 14.
    Athale UH, Puligandla M, Stevenson K, et al. Outcome of children and adolescents with down syndrome treated on Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium protocols 00-001 and 05-001. Pediatr Blood Cancer. 2018;65:e27256.CrossRefGoogle Scholar
  15. 15.
    Maloney KW, Wood B, Whitlock JA, et al. Event free (EFS) and overall survival (OS) for children with down syndrome (DS) and B-lymphoblastic leukemia in Children’s Oncology Group (COG) trials AALL0232 and AALL0331. Pediatr Blood Cancer. 2014;61:S1–4.CrossRefGoogle Scholar
  16. 16.
    Izraeli S, Vora A, Zwaan CM, Whitlock J. How I treat ALL in Down’s syndrome: pathobiology and management. Blood. 2014;123(1):35–40.CrossRefGoogle Scholar
  17. 17.
    Goto H, Inukai T, Inoue H, et al. Acute lymphoblastic leukemia and down syndrome: the collaborative study of the Tokyo Children’s cancer study group and the Kyushu Yamaguchi Children’s cancer study group. Int J Hematol. 2011;93(2):192–8.CrossRefGoogle Scholar
  18. 18.
    Whitlock JA, Sather HN, Gaynon P, et al. Clinical characteristics and outcome of children with down syndrome and acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood. 2005;106(13):4043–9.CrossRefGoogle Scholar
  19. 19.
    Lane AA, Chapuy B, Lin CY, et al. Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nat Genet. 2014;46(6):618–23.CrossRefGoogle Scholar
  20. 20.
    Thompson BJ, Bhansali R, Diebold L, et al. DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3. J Exp Med. 2015;212(6):953–70.CrossRefGoogle Scholar
  21. 21.
    Mullighan CG, Collins-Underwood JR, Phillips LA, et al. Rearrangement of CRLF2 in B-progenitor- and down syndrome-associated acute lymphoblastic leukemia. Nat Genet. 2009;41(11):1243–16.CrossRefGoogle Scholar
  22. 22.
    Potter N, Jones L, Blair H, et al. Single-cell analysis identifies CRLF2 rearrangements as both early and late events in down syndrome and non-down syndrome acute lymphoblastic leukaemia. Leukemia. 2019;33(4):893–904.CrossRefGoogle Scholar
  23. 23.
    Laetsch TW, Maude SL, Grupp S, et al. CTL019 therapy appears safe and effective in pediatric patients with down syndrome with relapsed/refractory (r/r) acute lymphoblastic leukemia. Blood. 2017;130:1280.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of PediatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan

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