Skip to main content
SpringerLink
Log in

Therapy of Acute Myelogenous Leukemia in Adults

  • Chapter
  • First Online:
Acute Myelogenous Leukemia

Part of the book series: Cancer Treatment and Research ((CTAR,volume 145))

  • 2455 Accesses

Abstract

The clinical and biological heterogeneity of adult acute myelogenous leukemia (AML) is increasingly apparent. Incorporation of cytogenetic data into the WHO classification of AML [1] is a testament to the importance of disease biology in treatment outcomes. Therefore the approach to treatment of AML in adults need to be based on a risk-stratified approach, the risk being that of relapse or refractory disease not responding to induction chemotherapy. Another risk that needs to be considered in making treatment decisions particularly in elderly patients or those with poor-performance status and organ dysfunction is that of induction-related death. Co-morbidity indices can conceivably identify patients with higher possibility of induction-related death [2,3] and prospective application of such indices will help to resolve the question of whether less than intensive chemotherapy can impact outcome in this group. This review will focus on drug therapy of AML and not on the hematopoietic stem cell transplant (HSCT).

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 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 54.99
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. Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood. 2005;105:1810–1814.

    Article  CAS  PubMed  Google Scholar 

  2. Amadori S, Suciu S, Stasi R, et al. Gemtuzumab ozogamicin (Mylotarg) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups. Leukemia. 2005;19:1768–1773.

    Article  CAS  PubMed  Google Scholar 

  3. Amadori S, Suciu S, Willemze R, et al. Sequential administration of gemtuzumab ozogamicin and conventional chemotherapy as first line therapy in elderly patients with acute myeloid leukemia: a phase II study (AML-15) of the EORTC and GIMEMA leukemia groups. Haematologica. 2004;89:950–956.

    CAS  PubMed  Google Scholar 

  4. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–3485.

    Article  CAS  PubMed  Google Scholar 

  5. Appelbaum FR, Pearce SF. Hematopoietic cell transplantation in first complete remission versus early relapse. Best Pract Res Clin Haematol. 2006;19:333–339.

    Article  PubMed  Google Scholar 

  6. Becker PS. Growth factor priming in therapy of acute myelogenous leukemia. Curr Hematol Rep. 2004;3:413–418.

    PubMed  Google Scholar 

  7. Bishop JF, Matthews JP, Young GA, et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996;87:1710–1717.

    CAS  PubMed  Google Scholar 

  8. 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;58:4173–4179.

    CAS  PubMed  Google Scholar 

  9. Breems DA, Van Putten WL, Huijgens PC, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005;23:1969–1978.

    Article  PubMed  Google Scholar 

  10. Buccisano F, Maurillo L, Gattei V, et al. The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia. Leukemia. 2006.

    Google Scholar 

  11. Buchner T, Hiddemann W, Wormann B, et al. Hematopoietic growth factors in acute myeloid leukemia: supportive and priming effects. Semin Oncol. 1997;24:124–131.

    CAS  PubMed  Google Scholar 

  12. 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;17:3767–3775.

    CAS  PubMed  Google Scholar 

  13. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325–4336.

    Article  CAS  PubMed  Google Scholar 

  14. Byrd JC, Ruppert AS, Mrozek 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;22:1087–1094.

    Article  CAS  PubMed  Google Scholar 

  15. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107:3463–3468.

    Article  CAS  PubMed  Google Scholar 

  16. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–1251.

    Article  CAS  PubMed  Google Scholar 

  17. de Labarthe A, Pautas C, Thomas X, et al. Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia. Bone Marrow Transplant. 2005;35:767–773.

    Article  PubMed  Google Scholar 

  18. Delaunay J, Vey N, Leblanc T, et al. Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup. Blood. 2003;102:462–469.

    Article  CAS  PubMed  Google Scholar 

  19. Dohner K, Tobis K, Ulrich R, et al. Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm. J Clin Oncol. 2002;20:3254–3261.

    Article  PubMed  CAS  Google Scholar 

  20. Estey E, de Lima M,Tibes R, et al. Prospective feasibility analysis of reduced intensity conditioning regimens (RIC) for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2007;109:1395–1400.

    Google Scholar 

  21. Estey E, Kornblau S, Pierce S, et al. A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia. Blood. 1996;88:756.

    CAS  PubMed  Google Scholar 

  22. Estey E, Thall P, Andreeff M, et al. Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol. 1994;12:671–678.

    CAS  PubMed  Google Scholar 

  23. Estey EH, Kantarjian HM, O'Brien S, et al. High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CSF). Cytokines Mol Ther. 1995;1:21–28.

    CAS  PubMed  Google Scholar 

  24. Estey EH, Thall PF, Cortes JE, et al. Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts. Blood. 2001;98:3575–3583.

    Article  CAS  PubMed  Google Scholar 

  25. Estey EH. General approach to, and perspectives on clinical research in, older patients with newly diagnosed acute myeloid leukemia. Semin Hematol. 2006;43:89–95.

    Article  PubMed  Google Scholar 

  26. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–266.

    Article  CAS  PubMed  Google Scholar 

  27. Feller N, van der Pol MA, van Stijn A, et al. MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia. Leukemia. 2004;18:1380–1390.

    Article  CAS  PubMed  Google Scholar 

  28. Fung HC, Stein A, Slovak M, et al. A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome. Biol Blood Marrow Transplant. 2003;9:766–771.

    Article  CAS  PubMed  Google Scholar 

  29. Gale RE, Hills R, Kottaridis PD, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood. 2005;106:3658–3665.

    Article  CAS  PubMed  Google Scholar 

  30. Goldstone AH, Burnett AK, Wheatley K, et al. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1302–1311.

    Article  CAS  PubMed  Google Scholar 

  31. Gorello P, Cazzaniga G, Alberti F, et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia. 2006;20:1103–1108.

    Article  CAS  PubMed  Google Scholar 

  32. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–1320.

    Article  CAS  PubMed  Google Scholar 

  33. Grimwade D, Walker H, Oliver F, et al. 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. 1998;92:2322–2333.

    CAS  PubMed  Google Scholar 

  34. Haferlach T, Kern W, Schoch C, et al. A new prognostic score for patients with acute myeloid leukemia based on cytogenetics and early blast clearance in trials of the German AML Cooperative Group. Haematologica. 2004;89:408–418.

    PubMed  Google Scholar 

  35. Heil G, Krauter J, Raghavachar, A et al. Risk-adapted induction and consolidation therapy in adults with de novo AML aged </= 60 years: results of a prospective multicenter trial. Ann Hematol. 2004;83:336–344.

    Article  CAS  PubMed  Google Scholar 

  36. Kantarjian H, O'Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090–1098.

    Article  PubMed  Google Scholar 

  37. Kern W, Haferlach T, Schoch C, et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. Blood. 2003;101:64–70.

    Article  CAS  PubMed  Google Scholar 

  38. Kern W, Haferlach T, Schoch C, et al. Risk-adapted therapy of AML: the AMLCG experience. Ann Hematol. 2004;83(suppl 1):S49–S51.

    PubMed  Google Scholar 

  39. Knapper S, Mills KI, Gilkes AF, et al. The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3 mutated and wild type cases. Blood. 2006;108:3494–3503.

    Google Scholar 

  40. Lapillonne H, Renneville A, Auvrignon A, et al. High WT1 expression after induction therapy predicts high risk of relapse and death in pediatric acute myeloid leukemia. J Clin Oncol. 2006;24:1507–1515.

    Article  CAS  PubMed  Google Scholar 

  41. List AF, Kopecky KJ, Willman CL, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2001;98:3212–3220.

    Article  CAS  PubMed  Google Scholar 

  42. Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology (Am Soc Hematol Educ Program). 2003;82–101.

    Google Scholar 

  43. Lowenberg B, Suciu S, Archimbaud E, et al. Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy–the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol. 1998;16:872–881.

    CAS  PubMed  Google Scholar 

  44. 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 

  45. Moore JO, George SL, Dodge RK, et al. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005;105:3420–3427.

    Article  CAS  PubMed  Google Scholar 

  46. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10:1911–1918.

    CAS  PubMed  Google Scholar 

  47. Nguyen S, Leblanc T, Fenaux P, et al. A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML): a survey of 161 cases from the French AML Intergroup. Blood. 2002;99:3517–3523.

    Article  CAS  PubMed  Google Scholar 

  48. O'Brien S, Kantarjian HM, Keating M, et al. Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21. J Clin Oncol. 1989;7:1081–1086.

    PubMed  Google Scholar 

  49. Perea G, Lasa A, Aventin A, et al. Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)]. Leukemia. 2006;20:87–94.

    Article  CAS  PubMed  Google Scholar 

  50. Platzbecker U, Thiede C, Fussel M, et al. Reduced intensity conditioning allows for up-front allogeneic hematopoietic stem cell transplantation after cytoreductive induction therapy in newly-diagnosed high-risk acute myeloid leukemia. Leukemia. 2006;20:707–714.

    Article  CAS  PubMed  Google Scholar 

  51. Russo D, Malagola M, de Vivo A, et al. Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Br J Haematol. 2005;131:172–179.

    Article  CAS  PubMed  Google Scholar 

  52. Schlenk RF, Benner A, Hartmann F, et al. Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial. Leukemia. 2003;17:1521–1528.

    Article  CAS  PubMed  Google Scholar 

  53. Schlenk RF, Benner A, Krauter J, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2004;22:3741–3750.

    Article  CAS  PubMed  Google Scholar 

  54. Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100:59–66.

    Article  CAS  PubMed  Google Scholar 

  55. Schnittger S, Schoch C, Kern W, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood. 2005;106:3733–3739.

    Article  CAS  PubMed  Google Scholar 

  56. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96:4075–4083.

    CAS  PubMed  Google Scholar 

  57. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–2919.

    Article  CAS  PubMed  Google Scholar 

  58. Stirewalt DL, Kopecky KJ, Meshinchi S, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107:3724–3726.

    Article  CAS  PubMed  Google Scholar 

  59. Stone RM, Berg DT, George SL, et al. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. N Engl J Med. 1995;332:1671–1677.

    Article  CAS  PubMed  Google Scholar 

  60. Stone RM, DeAngelo DJ, Klimek V, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005;105:54–60.

    Article  CAS  PubMed  Google Scholar 

  61. Stone RM, Fischer T, Paquette R, et al. Phase IB study of PKC412, an oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with daunorubicin and cytarabine (DA) induction and high-dose cytarabine consolidation in newly diagnosed patients with AML. ASH Abstract. 2006;#404.

    Google Scholar 

  62. Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology (Am Soc Hematol Educ Program). 2004;98–117.

    Google Scholar 

  63. Suciu S, Mandelli F, de Witte T, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood. 2003;102:1232–1240.

    Article  CAS  PubMed  Google Scholar 

  64. Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol. 1990;8:272–279.

    CAS  PubMed  Google Scholar 

  65. Usuki K, Urabe A, Masaoka T, et al. Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: a multicentre randomized study. Br J Haematol. 2002;116:103–112.

    Article  CAS  PubMed  Google Scholar 

  66. van der HB, Lowenberg B, Burnett AK, et al. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. Blood. 2005;106:2646–2654.

    Article  CAS  Google Scholar 

  67. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–2302.

    Article  CAS  PubMed  Google Scholar 

  68. Weisberg E, Boulton C, Kelly LM, et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell. 2002;1:433–443.

    Article  CAS  PubMed  Google Scholar 

  69. Wheatley K, Burnett AK, Goldstone AH, et al. 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. 1999;107:69–79.

    Article  CAS  PubMed  Google Scholar 

  70. Whitman SP, Liu S, Vukosavljevic T, et al. The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular-targeted therapy. Blood. 2005;106:345–352.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA

    Gautam Borthakur

  2. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Elihu E. Estey MD

Authors
  1. Gautam Borthakur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elihu E. Estey MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gautam Borthakur .

Editor information

Editors and Affiliations

  1. Dept. of Genetics, MD Anderson Cancer Center, Holcombe Blvd. 1515, Houston, 77030, USA

    Lalitha Nagarajan

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Borthakur, G., Estey, E.E. (2009). Therapy of Acute Myelogenous Leukemia in Adults. In: Nagarajan, L. (eds) Acute Myelogenous Leukemia. Cancer Treatment and Research, vol 145. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69259-3_15

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-69259-3_15

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-69257-9

  • Online ISBN: 978-0-387-69259-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation