Abstract
The acute myeloid leukemias (AML) represent a heterogeneous group of malignancies derived from the pluripotent hematopoietic stem cell. These leukemias are generally characterized by genetic lesions that result in a combination of defects causing unregulated proliferation of cells and defects in cellular maturation (Gilliland and Griffin 2002). AML accounts for approximately 15–20% of acute leukemia in children. In contrast to acute lymphoblastic leukemia (ALL) in childhood, for which an age-related peak incidence in children is associated with unique genetics, biology, and response to therapy, AML in children is very heterogeneous with large subsets representing disease that is generally similar to that in adults. Pediatric AML does not exhibit a dramatic peak in childhood other than for infants with disease involving translocation of the mixed lineage leukemia (MLL) gene. In both children and adults, AML is a relatively drug-resistant disease. Progress in improving outcome over the past 40 years has been associated with the use of pulses of high-dose, high systemic exposure intensive chemotherapy approaches. Refinements in chemotherapy regimens and major improvements in supportive care practices have resulted in the ability to achieve complete remission (CR) in 80–90% of pediatric patients and long-term event free survival (EFS) in 40–60% of patients. While high-dose chemotherapy Consolidation with hematopoietic stem cell transplantation (HSCT) once represented the predominant treatment approach, recent studies have revealed that large subgroups of patients characterized by specific cytogenetic and molecular features do not require transplantation as initial therapy. Conversely, other molecular analyses have identified very high risk subgroups at the time of initial diagnosis that possess highly resistant stem cell disease and are likely to benefit from stem cell transplantation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abbott BL, Rubnitz JE et al (2003) Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution’s experience. Leukemia 17(11):2090–2096
Abildgaard L, Ellebaek E et al (2006) 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 85(5):275–280
Abrahamsson J, Clausen N et al (2007) Improved outcome after relapse in children with acute myeloid leukaemia. Br J Haematol 136(2):229–236
Abu-Duhier FM, Goodeve AC et al (2000) FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol 111(1):190–195
Ades L, Chevret S et al (2006) Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol 24(36):5703–5710
Al-Ahmari A, Shah N et al (2006) 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 133(6):646–648
Appelbaum FR (1997) Allogeneic hematopoietic stem cell transplantation for acute leukemia. Semin Oncol 24(1):114–123
Appelbaum FR, Kopecky KJ et al (2006) The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol 135(2):165–173
Athale UH, Razzouk BI et al (2001) Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution’s experience. Blood 97(12):3727–3732
Baldus CD, Thiede C et al (2006) BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics: prognostic implications. J Clin Oncol 24(5):790–797
Balgobind BV, Raimondi SC et al (2009) Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 114(12):2489–2496
Barnard DR, Alonzo TA et al (2007) Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children’s Oncology Group. Pediatr Blood Cancer 49(1):17–22
Becton D, Dahl GV et al (2006) Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421. Blood 107(4):1315–1324
Bennett JM, Catovsky D et al (1976) Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33(4): 451–458
Bennett JM, Catovsky D et al (1985) Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 103(4):620–625
Bishop JF, Matthews JP et al (1998) Intensified induction chemotherapy with high dose cytarabine and etoposide for acute myeloid leukemia: a review and updated results of the Australian Leukemia Study Group. Leuk Lymph 28(3–4): 315–327
Bloomfield CD, Lawrence D et al (1998) Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 58(18):4173–4179
Boissel N, Leroy H et al (2006) Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 20(6):965–970
Breccia M, Carmosino I et al (2003) Early detection of meningeal localization in acute promyelocytic leukaemia patients with high presenting leucocyte count. Br J Haematol 120(2):266–270
Breems DA, Van Putten WL et al (2008) Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 26(29): 4791–4797
Brown P, McIntyre E et al (2007) The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood 110(3):979–985
Burnett AK, Grimwade D et al (1999) Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood 93(12):4131–4143
Burnett AK, Wheatley K et al (2002) The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 118(2):385–400
Burnett AK, Kell WJ et al (2006) The addition of Gemtuzumab Ozogamicin to induction chemotherapy for AML improves disease free survival without extra toxicity: preliminary analysis of 1115 patients in the MRC AML15 trial. ASH Annu Meeting Abstracts 108(11):13
Burnett AK, Hills RK et al (2009) Attempts to optimise induction and consolidation chemotherapy in patients with acute myeloid leukaemia: results of the MRC AML15 trial. ASH Annu Meeting Abstracts 114(22):484
Byrd JC, Dodge RK et al (1999) 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 17(12):3767–3775
Cabelof DC, Patel HV et al (2009) Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome. Blood 114(13):2753–2763
Campana D (2003) Determination of minimal residual disease in leukaemia patients. Br J Haematol 121(6):823–838
Campana D, Coustan-Smith E (2004) Minimal residual disease studies by flow cytometry in acute leukemia. Acta Haematol 112(1–2):8–15
Capizzi RL, Powell BL (1987) Sequential high-dose ara-C and asparaginase versus high-dose ara-C alone in the treatment of patients with relapsed and refractory acute leukemias. Semin Oncol 14(2 Suppl 1):40–50
Capizzi RL, Davis R et al (1988) Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia – a Cancer and Leukemia Group B study. J Clin Oncol 6(3):499–508
Cassileth PA, Harrington DP et al (1998) Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 339(23):1649–1656
Cazzaniga G, Dell’Oro MG et al (2005) Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype. Blood 106(4):1419–1422
Chard RL, Finklestein JZ et al (1978) Increased survival in childhood acute nonlymphocytic leukemia after treatment with prednisone, cytosine arabinoside, 6-thioguanine, cyclophosphamide, and oncovin (PATCO) combination chemotherapy. Med Pediatr Oncol 4(3):263–273
Cornelissen JJ, van Putten WL et al (2007) Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood 109(9):3658–3666
Coustan-Smith E, Ribeiro RC et al (2003) Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia. Br J Haematol 123(2):243–252
Craze JL, Harrison G et al (1999) Improved outcome of acute myeloid leukaemia in Down’s syndrome. Arch Dis Child 81(1):32–37
Creutzig U, Reinhardt D (2002) Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation? – a European view. Br J Haematol 118(2):365–377
Creutzig U, Ritter J et al (1987) The childhood AML studies BFM-78 and -83: treatment results and risk factor analysis. Haematol Blood Transfus 30:71–75
Creutzig U, Ritter J et al (1990) Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group. Blood 75(10):1932–1940
Creutzig U, Ritter J et al (1993) Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87. J Clin Oncol 11(2):279–286
Creutzig U, Ritter J et al (1996) Myelodysplasia and acute myelogenous leukemia in Down’s syndrome. A report of 40 children of the AML-BFM Study Group. Leukemia 10(11): 1677–1686
Creutzig U, Zimmermann M et al (1999) Definition of a standard-risk group in children with AML. Br J Haematol 104(3):630–639
Creutzig U, Reinhardt D et al (2001a) Intensive chemotherapy versus bone marrow transplantation in pediatric acute myeloid leukemia: a matter of controversies. Blood 97(11): 3671–3672
Creutzig U, Ritter J et al (2001b) 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-Munster 93. J Clin Oncol 19(10):2705–2713
Creutzig U, Reinhardt D et al (2005) AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity. Leukemia 19(8):1355–1360
Creutzig U, Zimmermann M et al (2006) Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98. J Clin Oncol 24(27):4499–4506
Dahl GV, Kalwinsky DK et al (1990) Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission. J Clin Oncol 8(2): 295–303
Dahl GV, Lacayo NJ et al (2000) Mitoxantrone, etoposide, and cyclosporine therapy in pediatric patients with recurrent or refractory acute myeloid leukemia. J Clin Oncol 18(9): 1867–1875
Dastugue N, Lafage-Pochitaloff M et al (2002) Cytogenetic pro-file of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Francais de Cytogenetique Hematologique (GFCH). Blood 100(2):618–626
De Botton S, Dombret H et al (1998) Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood 92(8):2712–2718
de Botton S, Chevret S et al (2003) Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial. Leukemia 17(2):339–342
de Botton S, Coiteux V et al (2004) Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin Oncol 22(8):1404–1412
de Botton S, Sanz MA et al (2006) Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Leukemia 20(1):35–41
Detourmignies L, Castaigne S et al (1992) Therapy-Related Acute Promyelocytic Leukemia – a Report on 16 Cases. J Clin Oncol 10(9):1430–1435
Dinndorf P, Bunin N (1995) Bone marrow transplantation for children with acute myelogenous leukemia. J Pediatr Hematol Oncol 17(3):211–224
Dinndorf PA, Andrews RG et al (1986) Expression of normal myeloid-associated antigens by acute leukemia cells. Blood 67(4):1048–1053
Diverio D, Rossi V et al (1998) Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter “AIDA” trial. GIMEMA-AIEOP Multicenter “AIDA” Trial. Blood 92(3):784–789
Dohner K, Schlenk RF et al (2005) Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 106(12): 3740–3746
Dohner H, Estey EH et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3):453–474
Entz-Werle N, Suciu S et al (2005) Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia 19(12):2072–2081
Estey E, Garcia-Manero G et al (2006) Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood 107(9): 3469–3473
Evans GD, Grimwade DJ (1999) Extramedullary disease in acute promyelocytic leukemia. Leuk Lymph 33(3–4): 219–229
Falini B, Mecucci C et al (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352(3):254–266
Fazi F, Travaglini L et al (2005) Retinoic acid targets DNA-methyltransferases and histone deacetylases during APL blast differentiation in vitro and in vivo. Oncogene 24(11): 1820–1830
Feig SA, Lampkin B et al (1993) Outcome of BMT during first complete remission of AML: a comparison of two sequential studies by the Children’s Cancer Group. Bone Marrow Transplant 12(1):65–71
Fenaux P, Chastang C et al (1999) A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood 94(4):1192–1200
Forestier E, Izraeli S et al (2008) Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study. Blood 111(3): 1575–1583
Frankel SR, Eardley A et al (1992) The “retinoic acid syndrome” in acute promyelocytic leukemia. Ann Intern Med 117(4): 292–296
Frost BM, Gustafsson G et al (2000) Cellular cytotoxic drug sensitivity in children with acute leukemia and Down’s syndrome: an explanation to differences in clinical outcome? Leukemia 14(5):943–944
Gale RE, Hills R et al (2005) Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia. Blood 106(12): 3768–3776
Gale RE, Green C et al (2008) The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 111(5): 2776–2784
Gamis AS (2005) Acute myeloid leukemia and Down syndrome evolution of modern therapy – state of the art review. Pediatr Blood Cancer 44(1):13–20
Gamis AS, Woods WG et al (2003) 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 21(18):3415–3422
Garderet L, Labopin M et al (2005) Hematopoietic stem cell transplantation for de novo acute megakaryocytic leukemia in first complete remission: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT). Blood 105(1):405–409
Ge Y, Stout ML et al (2005) GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia. J Natl Cancer Inst 97(3):226–231
George B, Mathews V et al (2004) Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience. Leukemia 18(10): 1587–1590
Ghavamzadeh A, Alimoghaddam K et al (2006) Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy. Ann Oncol 17(1):131–134
Gibson BE, Wheatley K et al (2005) Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials. Leukemia 19(12):2130–2138
Gilliland DG, Griffin JD (2002) The roles of FLT3 in hematopoiesis and leukemia. Blood 100(5):1532–1542
Girodon F, Favre B et al (2000) Immunophenotype of a transient myeloproliferative disorder in a newborn with trisomy 21. Cytometry 42(2):118–122
Goemans BF, Zwaan CM et al (2005) Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia 19(9): 1536–1542
Goemans BF, Tamminga RY et al (2008) Outcome for children with relapsed acute myeloid leukemia in the Netherlands following initial treatment between 1980 and 1998: survival after chemotherapy only? Haematologica 93(9): 1418–1420
Gregory J, Feusner J (2003) Acute promyelocytic leukaemia in children. Best Pract Res Clin Haematol 16(3):483–494
Grimwade D, Lo Coco F (2002) Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia 16(10):1959–1973
Grimwade D, Walker H et al (1998) The importance of diagnostic cytogenetics on outcome in AML: analysis of 1, 612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 92(7):2322–2333
Grimwade D, Biondi A et al (2000) Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Blood 96(4): 1297–1308
Grimwade D, Jovanovic JV et al (2009a) Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol 27(22):3650–3658
Grimwade J, Hills R et al (2010) National Cancer Research Institute Adult Leukaemia Working Group. Refinement of cytogenetic classification in acute myeloid leukaemia :determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated on United Kingdom Medical research Council trials.Blood 116(3):354–365
Groet J, McElwaine S et al (2003) Acquired mutations in GATA1 in neonates with Down’s syndrome with transient myeloid disorder. Lancet 361(9369):1617–1620
Hann IM, Stevens RF et al (1997) Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council’s 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Blood 89(7): 2311–2318
Harrison CJ, Hills RK et al (2010) Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol. Jun 1;28(16):2674–81. Epub 2010 May 3
Hasle H, Clemmensen IH et al (2000) Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet 355(9199):165–169
Hasle H, Alonzo TA et al (2007) Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood 109(11): 4641–4647
Hitzler JK, Cheung J et al (2003) GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood 101(11):4301–4304
Hollanda LM, Lima CS et al (2006) An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. Nat Genet 38(7): 807–812
Horan JT, Alonzo TA et al (2008) Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children’s Oncology Group. J Clin Oncol 26(35):5797–5801
Hubeek I, Stam RW et al (2005) The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br J Cancer 93(12): 1388–1394
Hurwitz CA, Schell MJ et al (1993) Adverse prognostic features in 251 children treated for acute myeloid leukemia. Med Pediatr Oncol 21(1):1–7
Karandikar NJ, Aquino DB et al (2001) Transient myeloproliferative disorder and acute myeloid leukemia in Down syndrome. An immunophenotypic analysis. Am J Clin Pathol 116(2):204–210
Kaspers GJ, Creutzig U (2005) Pediatric acute myeloid leukemia: international progress and future directions. Leukemia 19(12):2025–2029
Kaspers GLJ, Ravindranath Y (2005) Acute myeloid leukemia in children and adolescents. In: Degos L, Griffin JD, Linch DC, Lowenberg B (eds) Textbook of malignant haematology. London, Martin Dunitz, pp 617–632
Kaspers GJ, Zwaan CM (2007) Pediatric acute myeloid leukemia: towards high-quality cure of all patients. Haematologica 92(11):1519–1532
Kaspers GJL, Zimmermann M et al (2008) Prognostic significance of time to relapse in pediatric AML: results from the International Randomised Phase III Study Relapsed AML 2001/01. Blood (ASH Annu Meeting Abstracts) 112(11): 2976
Kaspers G, Gibson B et al (2009) Central nervous system involvement in relapsed acute promyelocytic leukemia. Pediatr Blood Cancer 53(2):235–236, author reply 237
Kell WJ, Burnett AK et al (2003) A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. Blood 102(13):4277–4283
Klusmann J-H, Creutzig U et al (2008) Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood 111(6):2991–2998
Klusmann J-H, Li Z et al (2010) miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia. Gene Dev 24(5):478–490
Knipp S, Gattermann N et al (2007) Arsenic in the cerebrospinal fluid of a patient receiving arsenic trioxide for relapsed acute promyelocytic leukemia with CNS involvement. Leuk Res 31(11):1585–1587
Kojima S, Sako M et al (2000) An effective chemotherapeutic regimen for acute myeloid leukemia and myelodysplastic syndrome in children with Down’s syndrome. Leukemia 14(5):786–791
Kottaridis PD, Gale RE et al (2001) 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 98(6):1752–1759
Kremer LCM, van Dalen EC et al (2001) Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 19(1):191–196
Krishnan K, Ross CW et al (1994) Neural cell-adhesion molecule (CD 56)-positive, t(8;21) acute myeloid leukemia (AML, M-2) and granulocytic sarcoma. Ann Hematol 69(6):321–323
Krivit W, Good RA (1957) Simultaneous occurrence of mongolism and leukemia; report of a nationwide survey. AMA J Dis Child 94(3):289–293
Kuerbitz SJ, Civin CI et al (1992) Expression of myeloid-associated and lymphoid-associated cell-surface antigens in acute myeloid leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol 10(9):1419–1429
Lange B (2000) The management of neoplastic disorders of haematopoiesis in children with Down’s syndrome. Br J Haematol 110(3):512–524
Lange BJ, Kobrinsky N et al (1998) 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 91(2):608–615
Lange BJ, Smith FO et al (2008) Outcomes in CCG-2961, a children’s oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children’s oncology group. Blood 111(3):1044–1053
Langebrake C, Creutzig U et al (2005) Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs significantly from other diseases with morphologically identical or similar blasts. Klin Padiatr 217(3):126–134
Langebrake C, Creutzig U et al (2006) Residual disease monitoring in childhood acute myeloid leukemia by multiparameter flow cytometry: the MRD-AML-BFM Study Group. J Clin Oncol 24(22):3686–3692
Lie SO, Jonmundsson G et al (1996) A population-based study of 272 children with acute myeloid leukaemia treated on two consecutive protocols with different intensity: best outcome in girls, infants, and children with Down’s syndrome. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Br J Haematol 94(1):82–88
Lie SO, Abrahamsson J et al (2003) Treatment stratification based on initial in vivo response in acute myeloid leukaemia in children without Down’s syndrome: results of NOPHO-AML trials. Br J Haematol 122(2):217–225
Lie SO, Abrahamsson J et al (2005) Long-term results in children with AML: NOPHO-AML Study Group – report of three consecutive trials. Leukemia 19(12): 2090–2100
Lo Coco F, Avvisati G et al (2004) Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation: results of the AIDA-2000 trial of the Italian GIMEMA Group. ASH Annu Meeting Abstracts 104(11):392
Lo Coco F, Ammatuna E et al (2007) Current treatment of acute promyelocytic leukemia. Haematologica 92(3): 289–291
Lowenberg B, Downing JR et al (1999) Acute myeloid leukemia. N Engl J Med 341(14):1051–1062
Malinge S, Izraeli S et al (2009) Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome. Blood 113(12):2619–2628
Mandelli F, Diverio D et al (1997) Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and Idarubicin (AIDA) therapy. Blood 90(3):1014–1021
Mann G, Reinhardt D et al (2001) Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children. Ann Hematol 80(7):417–422
Marcucci G, Mrozek K et al (2005) Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol 23(24): 5705–5717
Massey GV, Zipursky A 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):4606–4613
Mead AJ, Linch DC et al (2007) FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood 110(4):1262–1270
Meshinchi S, Woods WG et al (2001) Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 97(1):89–94
Meshinchi S, Stirewalt DL et al (2003) Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia. Blood 102(4):1474–1479
Meshinchi S, Alonzo TA et al (2006) Clinical implications of FLT3 mutations in pediatric AML. Blood 108(12): 3654–3661
Michel G, Baruchel A et al (1996) Induction chemotherapy followed by allogeneic bone marrow transplantation or aggressive consolidation chemotherapy in childhood acute myeloblastic leukemia. A prospective study from the French Society of Pediatric Hematology and Immunology (SHIP). Hematol Cell Ther 38(2): 169–176
Mikkola HKA, Radu CG et al (2010) Targeting leukemia stem cells. Nat Biotech 28(3):237–238
Milligan DW, Grimwade D et al (2006) Guidelines on the management of acute myeloid leukaemia in adults. Br J Haematol 135(4):450–474
Mistry AR, Pedersen EW et al (2003) The molecular pathogenesis of acute promyelocytic leukaemia: implications for the clinical management of the disease. Blood Rev 17(2):71–97
Mrozek K, Marcucci G et al (2007) Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 109(2):431–448
Mundschau G, Gurbuxani S et al (2003) Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Blood 101(11):4298–4300
Muramatsu H, Kato K et al (2008) Risk factors for early death in neonates with Down syndrome and transient leukaemia. Br J Haematol 142(4):610–615
Nesbit ME Jr, Buckley JD et al (1994) Chemotherapy for induction of remission of childhood acute myeloid leukemia followed by marrow transplantation or multiagent chemotherapy: a report from the Childrens Cancer Group. J Clin Oncol 12(1):127–135
Niu C, Yan H et al (1999) Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 94(10):3315–3324
O’Brien TA, Russell SJ et al (2002) Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children’s Cancer Study Group. Blood 100(8):2708–2716
O’Brien MM, Taub JW et al (2008) Cardiomyopathy in children with Down syndrome treated for acute myeloid leukemia: a report from the Children’s Oncology Group Study POG 9421. J Clin Oncol 26(3):414–420
Orfao A, Chillon M et al (1999) The flow cytometric pattern of CD34, CD15 and CD13 expression in acute myeloblastic leukemia is highly characteristic of the presence of PML-RARalpha gene rearrangements. Haematologica 84(5): 405–412
Ortega JJ, Madero L et al (2005) Treatment with all-trans retinoic acid and anthracycline mono chemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA group. J Clin Oncol 23(30):7632–7640
Paschka P, Marcucci G et al (2006) Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 24(24):3904–3911
Paschka P, Marcucci G et al (2008) Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol 26(28): 4595–4602
Perel Y, Auvrignon A et al (2002) 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. Leucamie Aique Myeloide Enfant. J Clin Oncol 20(12): 2774–2782
Perel Y, Auvrignon A et al (2005) Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucemie Aigue Myeloblastique Enfant) Cooperative Group. Leukemia 19(12):2082–2089
Powell BL (2007) Effect of consolidation with arsenic trioxide (As2O3) on event-free survival (EFS) and overall survival (OS) among patients with newly diagnosed acute promyelocytic leukemia (APL): North American Intergroup Protocol C9710. ASCO Meeting Abstracts 25(18 Suppl):2
Pui CH (1995) Childhood leukemias. N Engl J Med 332(24): 1618–1630
Pui MH, Fletcher BD et al (1994) Granulocytic sarcoma in childhood leukemia: imaging features. Radiology 190(3): 698–702
Pui CH, Schrappe M et al (2004) Childhood and adolescent lymphoid and myeloid leukemia. Hematol Am Soc Hematol Educ Program 2004(1):118–145
Raimondi SC, Chang MN et al (1999) Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. Blood 94(11): 3707–3716
Rainis L, Bercovich D et al (2003) Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21. Blood 102(3):981–986
Rao A, Hills RK 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):576–583
Ravandi F, Estey E et al (2009) Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol 27(4): 504–510
Ravindranath Y, Steuber CP et al (1991) High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study. J Clin Oncol 9(4):572–580
Ravindranath Y, Abella E et al (1992) Acute myeloid leukemia (AML) in Down’s syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. Blood 80(9):2210–2214
Ravindranath Y, Yeager AM et al (1996) Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group. N Engl J Med 334(22):1428–1434
Razzouk BI, Estey E et al (2006) Impact of age on outcome of pediatric acute myeloid leukemia: a report from 2 institutions. Cancer 106(11):2495–2502
Reinhardt D, Diekamp S et al (2005) Acute megakaryoblastic leukemia in children and adolescents, excluding Down’s syndrome: improved outcome with intensified induction treatment. Leukemia 19(8):1495–1496
Reinhardt D, Kremens B et al (2006) No improvement of overall-survival in children with high-risk acute myeloid leukemia by stem cell transplantation in 1st complete remission. ASH Annu Meeting Abstracts 108(11):320
Ribeiro RC, Razzouk BI et al (2005) Successive clinical trials for childhood acute myeloid leukemia at St Jude Children’s Research Hospital, from 1980 to 2000. Leukemia 19(12): 2125–2129
Roy A, Roberts I et al (2009) Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. Br J Haematol 147(1):3–12
Rubnitz JE, Raimondi SC et al (2002) Favorable impact of the t(9;11) in childhood acute myeloid leukemia. J Clin Oncol 20(9):2302–2309
Saito Y, Uchida N et al (2010) Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Nat Biotech 28(3):275–280
Sanz MA, Lo Coco F et al (2000) Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood 96(4): 1247–1253
Sanz MA, Martin G et al (2003) Choice of chemotherapy in induction, consolidation and maintenance in acute promyelocytic leukaemia. Best Pract Res Clin Haematol 16(3):433–451
Sanz MA, Martin G et al (2004) Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood 103(4):1237–1243
Sanz MA, Labopin M et al (2007) Hematopoietic stem cell transplantation for adults with acute promyelocytic leukemia in the ATRA era: a survey of the European Cooperative Group for Blood and Marrow Transplantation. Bone Marrow Transplant 39(8):461–469
Sanz MA, Grimwade D et al (2009) Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 113(9):1875–1891
Schlenk RF, Dohner K (2009) Impact of new prognostic markers in treatment decisions in acute myeloid leukemia. Curr Opin Hematol 16(2):98–104
Schlenk RF, Dohner K et al (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358(18):1909–1918
Schnittger S, Kohl TM et al (2006) KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood 107(5):1791–1799
Scholl S, Fricke HJ et al (2009) Clinical implications of molecular genetic aberrations in acute myeloid leukemia. J Cancer Res Clin Oncol 135(4):491–505
Shen ZX, Shi ZZ et al (2004) All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA 101(15):5328–5335
Shimada A, Xu G et al (2004) Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome. Blood 103(1):366
Shimada A, Taki T et al (2006) KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood 107(5):1806–1809
Sievers EL, Lange BJ et al (2003) Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children’s Cancer Group study of 252 patients with acute myeloid leukemia. Blood 101(9): 3398–3406
Smith FO, Lampkin BC et al (1992) Expression of lymphoid-associated cell surface antigens by childhood acute myeloid leukemia cells lacks prognostic significance. Blood 79(9): 2415–2422
Soignet SL, Frankel SR et al (2001) United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 19(18):3852–3860
Specchia G, Lo Coco F et al (2001) Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell’Adulto. J Clin Oncol 19(20):4023–4028
Stahnke K, Boos J et al (1998) Duration of first remission predicts remission rates and long-term survival in children with relapsed acute myelogenous leukemia. Leukemia 12(10):1534–1538
Steuber CP, Culbert SJ et al (1990) Therapy of childhood acute nonlymphocytic leukemia: the Pediatric Oncology Group experience (1977–1988). Haematol Blood Transfus 33: 198–209
Steuber CP, Civin C et al (1991) A comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood: results of a Pediatric Oncology Group study. J Clin Oncol 9(2):247–258
Stevens RF, Hann IM et al (1998) 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 101(1):130–140
Tallman MS (2007) Treatment of relapsed or refractory acute promyelocytic leukemia. Best Pract Res Clin Haematol 20(1):57–65
Tallman MS, Hakimian D et al (1993) Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia. J Clin Oncol 11(4):690–697
Tallman MS, Andersen JW et al (1997) All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 337(15): 1021–1028
Taub JW, Ge Y (2005) Down syndrome, drug metabolism and chromosome 21. Pediatr Blood Cancer 44(1):33–39
Taub JW, Huang X et al (1999) Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. Blood 94(4):1393–1400
Testi AM, Biondi A et al (2005) GIMEMA-AIEOP AIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood 106(2):447–453
Thiede C, Steudel C et al (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99(12):4326–4335
Thiede C, Koch S et al (2006) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 107(10):4011–4020
Tomizawa D, Tabuchi K et al (2007) 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 49(2):127–132
Tsukimoto I, Tawa A et al (2009) 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 27(24):4007–4013
Vardiman JW, Harris NL et al (2002) The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100(7):2292–2302
Vardiman JW, Thiele J et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951
Vaughan W, Karp J et al (1984) Two-cycle timed-sequential chemotherapy for adult acute nonlymphocytic leukemia. Blood 64(5):975–980
Vicente D, Lamparelli T et al (2007) Improved outcome in young adults with de novo acute myeloid leukemia in first remission, undergoing an allogeneic bone marrow transplant. Bone Marrow Transplant 40(4):349–354
Webb DK, Wheatley K et al (1999) Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial. MRC Childhood Leukaemia Working Party. Leukemia 13(1):25–31
Wechsler J, Greene M et al (2002) Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet 32(1):148–152
Weick JK, Kopecky KJ et al (1996) A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood 88(8):2841–2851
Weinstein HJ, Mayer RJ et al (1980) Treatment of acute myelogenous leukemia in children and adults. N Engl J Med 303(9):473–478
Wells R, Woods W et al (1994a) Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study. J Clin Oncol 12(11): 2367–2377
Wells RJ, Odom LF et al (1994b) Cytosine arabinoside and mitoxantrone treatment of relapsed or refractory childhood leukemia: initial response and relationship to multidrug resistance gene 1. Med Pediatr Oncol 22(4):244–249
Wheatley K (2002) Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation? A statistician’s view. Br J Haematol 118(2):351–356
Wheatley K, Burnett AK et al (1999) A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council’s Adult and Childhood Leukaemia Working Parties. Br J Haematol 107(1):69–79
Whitman SP, Archer KJ et al (2001) Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res 61(19):7233–7239
Woods WG, Ruymann FB et al (1990) The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia. Cancer 66(6):1106–1113
Woods WG, Kobrinsky N et al (1996) Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: a report from the Children’s Cancer Group. Blood 87(12):4979–4989
Woods WG, Neudorf S et al (2001) A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission: a report from the Children’s Cancer Group. Blood 97(1):56–62
Wouters BJ, Lowenberg B et al (2009) Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 113(13):3088–3091
Xu G, Nagano M et al (2003) Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood 102(8):2960–2968
Yates JW, Wallace HJ Jr et al (1973) Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 57(4):485–488
Yates J, Glidewell O et al (1982) Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 60(2):454–462
Yumura-Yagi K, Hara J et al (1992) Mixed phenotype of blasts in acute megakaryocytic leukaemia and transient abnormal myelopoiesis in Down’s syndrome. Br J Haematol 81(4): 520–525
Zeller B, Gustafsson G et al (2005) Acute leukaemia in children with Down syndrome: a population-based Nordic study. Br J Haematol 128(6):797–804
Zipursky A (2003) Transient leukaemia – a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol 120(6):930–938
Zipursky A, Thorner P et al (1994) Myelodysplasia and acute megakaryoblastic leukemia in Down’s syndrome. Leuk Res 18(3):163–171
Zwaan CM, Kaspers GJL (2004) Possibilities for tailored and targeted therapy in paediatric acute myeloid leukaemia. Br J Haematol 127(3):264–279
Zwaan CM, Kaspers GJ et al (2002) Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood 99(1):245–251
Zwaan CM, Meshinchi S et al (2003a) FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood 102(7):2387–2394
Zwaan CM, Reinhardt D et al (2003b) Gemtuzumab ozogamicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated on compassionate-use basis. Blood 101(10):3868–3871
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Berlin Heidelberg
About this chapter
Cite this chapter
Gibson, B., Perentesis, J., Alonzo, T.A., Kaspers, G.J.L. (2011). Treatment of Acute Myeloid Leukemia. In: Reaman, G., Smith, F. (eds) Childhood Leukemia. Pediatric Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13781-5_5
Download citation
DOI: https://doi.org/10.1007/978-3-642-13781-5_5
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-13780-8
Online ISBN: 978-3-642-13781-5
eBook Packages: MedicineMedicine (R0)