Skip to main content
SpringerLink
Log in

Acute Myeloid Leukemia

  • Chapter
  • First Online:
Book cover Hematological Disorders in Children

  • 977 Accesses

Abstract

Acute myeloid leukemia (AML) is a rare type of childhood cancer. With tremendous efforts by the collaborative study groups worldwide in the past decades, survival rates have currently reached approximately 70% in de novo AML and 80% in myeloid leukemia associated with Down syndrome and acute promyelocytic leukemia (APL). Advance in genomic analyses would contribute to further understanding of the pathobiology of AML, which is expected to result in development of better risk stratification, novel molecular targeted therapy, and finally to overcome the disease in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Horibe K, Takimoto T, Tsuchida M, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013;98:74–88.

    Article  PubMed  Google Scholar 

  2. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    Article  CAS  PubMed  Google Scholar 

  3. Creutzig U, van den Heuvel-Eibrink MM, Gibson B, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood. 2012;120:3187–205.

    Article  CAS  PubMed  Google Scholar 

  4. Arthur DC, Bloomfield CD. Association of partial deletion of the long arm of chromosome 16 and bone marrow eosinophilia in acute non-lymphocytic leukemia. Blood. 1983;62:931.

    CAS  PubMed  Google Scholar 

  5. Argyle JC, Benjamin DR, Lampkin B, Hammond D. Acute nonlymphocytic leukemias of childhood. Inter-observer variability and problems in the use of the FAB classification. Cancer. 1989;63:295–301.

    Article  CAS  PubMed  Google Scholar 

  6. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.

    Article  PubMed  Google Scholar 

  7. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–302.

    Article  CAS  PubMed  Google Scholar 

  8. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.

    Article  CAS  PubMed  Google Scholar 

  9. Kinoshita A, Miyachi H, Matsushita H, et al. Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group. Br J Haematol. 2014;167:80–6.

    Article  CAS  PubMed  Google Scholar 

  10. Bacher U, Schnittger S, Macijewski K, et al. Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood. 2012;119:4719–22.

    Article  CAS  PubMed  Google Scholar 

  11. Falini B, Macijewski K, Weiss T, et al. Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood. 2010;115:3776–86.

    Article  CAS  PubMed  Google Scholar 

  12. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002;100:1532–42.

    Article  CAS  PubMed  Google Scholar 

  13. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.

    Article  CAS  PubMed  Google Scholar 

  14. Radtke I, Mullighan CG, Ishii M, et al. Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proc Natl Acad Sci U S A. 2009;106:12944–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Klein K, Kaspers G, Harrison CJ, et al. Clinical impact of additional cytogenetic aberrations, cKIT and RAS mutations, and treatment elements in pediatric t(8;21)-AML: results from an International Retrospective Study by the International Berlin-Frankfurt-Münster Study Group. J Clin Oncol. 2015;33:4247–58.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Goemans BF, Zwaan CM, Miller M, et al. Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia. 2005;19:1536–42.

    Article  CAS  PubMed  Google Scholar 

  17. Pollard JA, Alonzo TA, Gerbing RB, et al. Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood. 2010;115:2372–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shimada A, Ichikawa H, Taki T, et al. Low frequency of KIT gene mutation in pediatric acute myeloid leukemia with inv(16)(p13q22): a study of the Japanese Childhood AML Cooperative Study Group. Int J Hematol. 2007;86:289–90.

    Article  CAS  PubMed  Google Scholar 

  19. Tokumasu M, Murata C, Shimada A, et al. Adverse prognostic impact of KIT mutations in childhood CBF-AML: the results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial. Leukemia. 2015;29:2438–41.

    Article  CAS  PubMed  Google Scholar 

  20. Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30:41–7.

    Article  CAS  PubMed  Google Scholar 

  21. Meyer C, Hofmann J, Burmeister T, et al. The MLL recombinome of acute leukemias in 2013. Leukemia. 2013;27:2165–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Balgobind BV, Raimondi SC, Harbott J, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009;114:2489–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Matsuo H, Kajihara M, Tomizawa D, et al. EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia. Haematologica. 2014;99:e225–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Reinhardt D, Diekamp S, Langebrake C, et al. Acute megakaryoblastic leukemia in children and adolescents, excluding Down’s syndrome: improved outcome with intensified induction treatment. Leukemia. 2005;19:1495–6.

    Article  CAS  PubMed  Google Scholar 

  25. Schweitzer J, Zimmermann M, Rasche M, et al. Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial. Ann Hematol. 2015;94:1327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Inaba H, Zhou Y, Abla O, et al. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. Blood. 2015;126:1575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. de Rooij JDE, Hollink IHIM, Arentsen-Peters STCJM, et al. NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern. Leukemia. 2013;27:2280–8.

    Article  PubMed  CAS  Google Scholar 

  28. Gruber TA, Larson Gedman A, Zhang J, et al. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell. 2012;22:683–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. de Rooij JDE, Masetti R, van den Heuvel-Eibrink MM, et al. Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study. Blood. 2016;127:3424–30.

    Article  PubMed  CAS  Google Scholar 

  30. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–9.

    Article  CAS  PubMed  Google Scholar 

  31. Meshinchi S, Woods WG, Stirewalt DL, et al. Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood. 2001;97:89–94.

    Article  CAS  PubMed  Google Scholar 

  32. Zwaan CM, Meshinchi S, Radich JP, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood. 2003;102:2387–94.

    Article  CAS  PubMed  Google Scholar 

  33. Hollink IHIM, van den Heuvel-Eibrink MM, Arentsen-Peters STCJM, et al. NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood. 2011a;118:3645–56.

    Article  CAS  PubMed  Google Scholar 

  34. Hasle H, Alonzo TA, Auvrignon A, et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109:4641–7.

    Article  CAS  PubMed  Google Scholar 

  35. Johnston DL, Alonzo TA, Gerbing RB, et al. Outcome of pediatric patients with acute myeloid leukemia (AML) and −5/5q- abnormalities from five pediatric AML treatment protocols: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2013;60:2073–8.

    Article  PubMed  Google Scholar 

  36. Brown P, McIntyre E, Rau R, et al. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood. 2007;110:979–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ho PA, Alonzo TA, Gerbing RB, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood. 2009;113:6558–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hollink IHIM, van den Heuvel-Eibrink MM, Arentsen-Peters STCJM, et al. Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia. Haematologica. 2011b;96:384–92.

    Article  CAS  PubMed  Google Scholar 

  39. Hollink IHIM, Zwaan CM, Zimmermann M, et al. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia. 2009;23:262–70.

    Article  CAS  PubMed  Google Scholar 

  40. Shiba N, Funato M, Ohki K, et al. Mutations of the GATA2 and CEBPA genes in paediatric acute myeloid leukaemia. Br J Haematol. 2013;164:142–5.

    Article  PubMed  CAS  Google Scholar 

  41. Inaba H, Coustan-Smith E, Cao X, et al. Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. J Clin Oncol. 2012;30:3625–32.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Karol SE, Coustan-Smith E, Cao X, et al. Prognostic factors in children with acute myeloid leukaemia and excellent response to remission induction therapy. Br J Haematol. 2015;168:94–101.

    Article  PubMed  Google Scholar 

  43. Yates J, Glidewell O, Wiernik P, et al. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood. 1982;60:454–62.

    CAS  PubMed  Google Scholar 

  44. Dillman RO, Davis RB, Green MR, et al. A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood. 1991;78:2520–6.

    CAS  PubMed  Google Scholar 

  45. Tomizawa D, Tabuchi K, Kinoshita A, et al. Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: long-term outcome of the children with AML treated on two consecutive trials of Tokyo Children’s Cancer Study Group. Pediatr Blood Cancer. 2007;49:127–32.

    Article  PubMed  Google Scholar 

  46. Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2009;27:4007–13.

    Article  CAS  PubMed  Google Scholar 

  47. Becton D, Dahl GV, Ravindranath Y, et al. Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421. Blood. 2006;107:1315–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rubnitz JE, Inaba H, Dahl G, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010;11:543–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gibson BES, Wheatley K, Hann IM, et al. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials. Leukemia. 2005;19:2130–8.

    Article  CAS  PubMed  Google Scholar 

  50. Creutzig U, Ritter J, Zimmermann M, et al. Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group. Leukemia. 2001a;15:348–54.

    Article  CAS  PubMed  Google Scholar 

  51. Gibson BES, Webb DKH, Howman AJ, et al. Results of a randomized trial in children with Acute Myeloid Leukaemia: medical research council AML12 trial. Br J Haematol. 2011;155:366–76.

    Article  CAS  PubMed  Google Scholar 

  52. Creutzig U, Zimmermann M, Bourquin J-P, et al. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122:37–43.

    Article  CAS  PubMed  Google Scholar 

  53. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361:1249–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lowenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235–48.

    Article  PubMed  Google Scholar 

  55. Stevens RF, Hann IM, Wheatley K, Gray RG. Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council’s 10th AML trial. MRC Childhood Leukaemia Working Party. Br J Haematol. 1998;101:130–40.

    Article  CAS  PubMed  Google Scholar 

  56. Arceci RJ, Sande J, Lange B, et al. Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia. Blood. 2005;106:1183–8.

    Article  CAS  PubMed  Google Scholar 

  57. Zwaan CM, Reinhardt D, Zimmerman M, et al. Salvage treatment for children with refractory first or second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin: results of a phase II study. Br J Haematol. 2010;148:768–76.

    Article  CAS  PubMed  Google Scholar 

  58. Petersdorf SH, Kopecky KJ, Slovak M, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121:4854–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011;29:369–77.

    Article  CAS  PubMed  Google Scholar 

  60. Castaigne S, Pautas C, Terré C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012;379:1508–16.

    Article  CAS  PubMed  Google Scholar 

  61. Gamis AS, Alonzo TA, Meshinchi S, et al. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014;32:3021–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cassileth PA, Harrington DP, Hines JD, et al. Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia. J Clin Oncol. 1988;6:583–7.

    Article  CAS  PubMed  Google Scholar 

  63. Bloomfield CD, Lawrence D, Byrd JC, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res. 1998;58:4173–9.

    CAS  PubMed  Google Scholar 

  64. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994;331:896–903.

    Article  CAS  PubMed  Google Scholar 

  65. Byrd JC, Dodge RK, Carroll A, et al. Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered. J Clin Oncol. 1999;17:3767–75.

    Article  CAS  PubMed  Google Scholar 

  66. Byrd JC, Ruppert AS, Mrózek K, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): results from CALGB 8461. J Clin Oncol. 2004;22:1087–94.

    Article  CAS  PubMed  Google Scholar 

  67. Creutzig U, Ritter J, Zimmermann M, et al. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93. J Clin Oncol. 2001b;19:2705–13.

    Article  CAS  PubMed  Google Scholar 

  68. Creutzig U, Zimmermann M, Bourquin J-P, et al. Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16). Blood. 2011;118:5409–15.

    Article  CAS  PubMed  Google Scholar 

  69. Hasegawa D, Tawa A, Tomizawa D, et al. Attempts to optimize post-induction treatment in childhood acute myeloid leukemia without core binding factors: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Blood. 2012;120:3545a.

    Google Scholar 

  70. Tomizawa D, Tawa A, Watanabe T, et al. Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children. Leukemia. 2013a;27:2413–6.

    Article  CAS  PubMed  Google Scholar 

  71. Perel Y, Auvrignon A, LeBlanc T, et al. Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucámie Aiqüe Myéloïde Enfant. J Clin Oncol. 2002;20:2774–82.

    Article  PubMed  Google Scholar 

  72. Creutzig U, Zimmermann M, Ritter J, et al. Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia. 2005b;19:2030–42.

    Article  CAS  PubMed  Google Scholar 

  73. Pui C-H, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol. 2008;9:257–68.

    Article  PubMed  Google Scholar 

  74. Woods WG, Neudorf S, Gold S, et al. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood. 2001;97:56–62.

    Article  CAS  PubMed  Google Scholar 

  75. Niewerth D, Creutzig U, Bierings MB, Kaspers GJL. A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood. 2010;116:2205–14.

    Article  CAS  PubMed  Google Scholar 

  76. Leung W, Campana D, Yang J, et al. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood. 2011;118:223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Michel G, Rocha V, Chevret S, et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood. 2003;102:4290–7.

    Article  CAS  PubMed  Google Scholar 

  78. Copelan EA, Hamilton BK, Avalos B, et al. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013;122:3863–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. de Berranger E, Cousien A, Petit A, et al. Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Bone Marrow Transplant. 2014;49:382–8.

    Article  PubMed  CAS  Google Scholar 

  80. Bitan M, He W, Zhang M-J, et al. Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens. Blood. 2014;123:1615–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ishida H, Adachi S, Hasegawa D, et al. Comparison of a fludarabine and melphalan combination-based reduced toxicity conditioning with myeloablative conditioning by radiation and/or busulfan in acute myeloid leukemia in Japanese children and adolescents. Pediatr Blood Cancer. 2014;21:2141–7.

    Google Scholar 

  82. Nagler A, Rocha V, Labopin M, et al. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen—a report from the acute leukemia working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2013;31:3549–56.

    Article  CAS  PubMed  Google Scholar 

  83. Tomizawa D, Tawa A, Watanabe T, et al. Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group. Int J Hematol. 2013b;98:578–88.

    Article  CAS  PubMed  Google Scholar 

  84. Pession A, Masetti R, Rizzari C, et al. Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia. Blood. 2013;122:170–8.

    Article  CAS  PubMed  Google Scholar 

  85. Abrahamsson J, Forestier E, Heldrup J, et al. Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate. J Clin Oncol. 2011;29:310–5.

    Article  PubMed  Google Scholar 

  86. Hasle H, Abrahamsson J, Forestier E, et al. Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004. Blood. 2012;120:978–84.

    Article  CAS  PubMed  Google Scholar 

  87. Kaspers GJL, Zimmermann M, Reinhardt D, et al. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013;31:599–607.

    Article  CAS  PubMed  Google Scholar 

  88. Nakayama H, Tabuchi K, Tawa A, et al. Outcome of children with relapsed acute myeloid leukemia following initial therapy under the AML99 protocol. Int J Hematol. 2014;100:171–9.

    Article  CAS  PubMed  Google Scholar 

  89. Zwaan CM, Kolb EA, Reinhardt D, et al. Collaborative efforts driving progress in pediatric acute myeloid leukemia. J Clin Oncol. 2015;33:2949–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Parker SE, Mai CT, Canfield MA, et al. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010;88:1008–16.

    Article  CAS  PubMed  Google Scholar 

  91. Roizen NJ, Patterson D. Down’s syndrome. Lancet. 2003;361:1281–9.

    Article  PubMed  Google Scholar 

  92. Hasle H, Clemmensen IH, Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet. 2000;355:165–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  94. Lange BJ, Kobrinsky N, Barnard DR, 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.

    CAS  PubMed  Google Scholar 

  95. Roy A, Roberts I, Vyas P. Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome. Semin Fetal Neonatal Med. 2012;17:196–201.

    Article  PubMed  Google Scholar 

  96. Banno K, Omori S, Hirata K, et al. Systematic cellular disease models reveal synergistic interaction of Trisomy 21 and GATA1 mutations in hematopoietic abnormalities. Cell Rep. 2016;15:1228–41.

    Article  CAS  PubMed  Google Scholar 

  97. Yoshida K, Toki T, Okuno Y, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45:1293–9.

    Article  CAS  PubMed  Google Scholar 

  98. Zwaan CM, Kaspers GJL, Pieters R, 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.

    Article  CAS  PubMed  Google Scholar 

  99. Ge Y, Stout ML, Tatman DA, et al. GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia. J Natl Cancer Inst. 2005;97:226–31.

    Article  CAS  PubMed  Google Scholar 

  100. Ravindranath Y, Abella E, Krischer JP, et al. Acute myeloid leukemia (AML) in Down’s syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. Blood. 1992;80:2210–4.

    CAS  PubMed  Google Scholar 

  101. Creutzig U, Reinhardt D, Diekamp S, et al. AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity. Leukemia. 2005a;19:1355–60.

    Article  CAS  PubMed  Google Scholar 

  102. Gamis AS, Woods WG, Alonzo TA, et al. Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children’s Cancer Group Study 2891. J Clin Oncol. 2003;21:3415–22.

    Article  PubMed  Google Scholar 

  103. Rao A, Hills RK, Stiller C, et al. 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. 2006;132:576–83.

    Article  CAS  PubMed  Google Scholar 

  104. Abildgaard L, Ellebaek E, Gustafsson G, et al. Optimal treatment intensity in children with Down syndrome and myeloid leukaemia: data from 56 children treated on NOPHO-AML protocols and a review of the literature. Ann Hematol. 2006;85:275–80.

    Article  PubMed  Google Scholar 

  105. Sorrell AD, Alonzo TA, Hilden JM, et al. Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children’s Oncology Group trial A2971: a report from the Children’s Oncology Group. Cancer. 2012;118:4806–14.

    Article  CAS  PubMed  Google Scholar 

  106. Al-Ahmari A, Shah N, Sung L, et al. Long-term results of an ultra low-dose cytarabine-based regimen for the treatment of acute megakaryoblastic leukaemia in children with Down syndrome. Br J Haematol. 2006;133:646–8.

    Article  CAS  PubMed  Google Scholar 

  107. Kudo K, Kojima S, Tabuchi K, et al. Prospective study of a pirarubicin, intermediate-dose cytarabine, and etoposide regimen in children with Down syndrome and acute myeloid leukemia: the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2007;25:5442–7.

    Article  CAS  PubMed  Google Scholar 

  108. Taga T, Shimomura Y, Horikoshi Y, et al. Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children’s cancer and leukemia study group (JCCLSG) AML 9805 down study. Pediatr Blood Cancer. 2011;57:36–40.

    Article  PubMed  Google Scholar 

  109. Taga T, Watanabe T, Tomizawa D, et al. Preserved high probability of overall survival with significant reduction of chemotherapy for myeloid leukemia in Down syndrome: a nationwide prospective study in Japan. Pediatr Blood Cancer. 2016;63:248–54.

    Article  CAS  PubMed  Google Scholar 

  110. Taub JW, Berman JN, Hitzler JK, et al. Improvement in treatment outcome and identification of a new prognostic parameter in Down Syndrome Acute Myeloid Leukemia (DS-AML): Results of the Children’s Oncology Group (COG) Phase III AAML0431 Trial. Blood. 2014;124:278.

    Google Scholar 

  111. Kudo K, Hama A, Kojima S, et al. Mosaic Down syndrome-associated acute myeloid leukemia does not require high-dose cytarabine treatment for induction and consolidation therapy. Int J Hematol. 2010;91:630–5.

    Article  CAS  PubMed  Google Scholar 

  112. Blink M, Zimmermann M, Neuhoff von C, et al. Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study. Haematologica. 2014;99:299–307.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Taga T, Saito AM, Kudo K, et al. Clinical characteristics and outcome of refractory/relapsed myeloid leukemia in children with Down syndrome. Blood. 2012;120:1810–5.

    Article  CAS  PubMed  Google Scholar 

  114. Caldwell JT, Edwards H, Buck SA, et al. Targeting the wee1 kinase for treatment of pediatric Down syndrome acute myeloid leukemia. Pediatr Blood Cancer. 2014;61:1767–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Wen Q, Goldenson B, Silver SJ, et al. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell. 2012;150:575–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Stankov MV, Khatib El M, Kumar Thakur B, et al. Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy. Leukemia. 2014;28:577–88.

    Article  CAS  PubMed  Google Scholar 

  117. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875–91.

    Article  CAS  PubMed  Google Scholar 

  118. Kaleem Z, Crawford E, Pathan MH, et al. Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med. 2003;127:42–8.

    PubMed  Google Scholar 

  119. Tallman MS, Lefèbvre P, Baine RM, et al. Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost. 2004;2:1341–50.

    Article  CAS  PubMed  Google Scholar 

  120. de la Serna J, Montesinos P, Vellenga E, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008;111:3395–402.

    Article  PubMed  CAS  Google Scholar 

  121. Bally C, Fadlallah J, Leverger G, et al. Outcome of acute promyelocytic leukemia (APL) in children and adolescents: an analysis in two consecutive trials of the European APL Group. J Clin Oncol. 2012;30:1641–6.

    Article  CAS  PubMed  Google Scholar 

  122. Creutzig U, Zimmermann M, Dworzak M, et al. Favourable outcome of patients with childhood acute promyelocytic leukaemia after treatment with reduced cumulative anthracycline doses. Br J Haematol. 2010;149:399–409.

    Article  CAS  PubMed  Google Scholar 

  123. Imaizumi M, Tawa A, Hanada R, et al. Prospective study of a therapeutic regimen with all-trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia cooperative study. Br J Haematol. 2010;152:89–98.

    Article  CAS  Google Scholar 

  124. Kutny MA, Gregory J, Feusner JH. Treatment of paediatric APL: how does the therapeutic approach differ from adults? Best Pract Res Clin Haematol. 2014;27:69–78.

    Article  PubMed  Google Scholar 

  125. Ortega JJ, Madero L, Martín G, et al. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. J Clin Oncol. 2005;23:7632–40.

    Article  CAS  PubMed  Google Scholar 

  126. Takahashi H, Watanabe T, Kinoshita A, et al. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group. Br J Haematol. 2016;174:437–43.

    Article  CAS  PubMed  Google Scholar 

  127. Testi AM, Biondi A, Coco Lo F, et al. GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood. 2005;106:447–53.

    Article  CAS  PubMed  Google Scholar 

  128. Diverio D, Rossi V, Avvisati G, et al. Early Detection of Relapse by Prospective Reverse Transcriptase-Polymerase Chain Reaction Analysis of the PML/RARα Fusion Gene in Patients With Acute Promyelocytic Leukemia Enrolled in the GIMEMA-AIEOP Multicenter “AIDA” Trial. Blood. 1998;92:784–9.

    CAS  PubMed  Google Scholar 

  129. Esteve J, Escoda L, Martin G, et al. Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention. Leukemia. 2007;21:446–52.

    Article  CAS  PubMed  Google Scholar 

  130. Sanz MA, Fenaux P, Coco FL. Arsenic trioxide in the treatment of acute promyelocytic leukemia. A review of current evidence. Haematologica. 2005;90(9):1231–5.

    Google Scholar 

  131. Burnett AK, Russell NH, Hills RK, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16:1295–305.

    Article  CAS  PubMed  Google Scholar 

  132. Lo Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111–21.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Human Health Sciences, Kyoto University, Kyoto, Japan

    Souichi Adachi M.D., Ph.D.

  2. Department of Pediatrics, St. Marianna University School of Medicine, Kanagawa, Japan

    Akitoshi Kinoshita M.D., Ph.D.

  3. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Daisuke Tomizawa M.D., Ph.D.

  4. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan

    Takashi Taga M.D., Ph.D.

  5. Department of Pediatrics, Toho University, Tokyo, Japan

    Hiroyuki Takahashi M.D., Ph.D.

Authors
  1. Souichi Adachi M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akitoshi Kinoshita M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Tomizawa M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Taga M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyuki Takahashi M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Souichi Adachi M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan

    Eiichi Ishii

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Adachi, S., Kinoshita, A., Tomizawa, D., Taga, T., Takahashi, H. (2017). Acute Myeloid Leukemia. In: Ishii, E. (eds) Hematological Disorders in Children. Springer, Singapore. https://doi.org/10.1007/978-981-10-3886-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-3886-0_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-3885-3

  • Online ISBN: 978-981-10-3886-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation