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Treatment of Adult Acute Myelogenous Leukemia

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Treatment of Acute Leukemias

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

Historically, the classification and treatment of acute myelogenous leukemia (AML) has been based on morphologic and clinical observations. The identification of the molecular events involved in the pathogenesis of human tumors, including the acute leukemias, has refined their classification and understanding. In AML, a large number of leukemia-specific cytogenetic abnormalities have been identified and the involved genes cloned. These studies have helped elucidate the molecular pathways that may be involved in cellular transformation and have provided methods for the monitoring of patients after chemotherapy as well as evaluating treatment responses based on various clinical, phenotypic, and genetic risk factors. Table 1 lists the consistent cytogenetic abnormalities found in AML and their unique gene products (1). Although the leukemic cells in many patients do not have detectable structural chromosomal changes at diagnosis, some may harbor molecular changes not apparent on routine karyotyping such as those involving the MLL gene (2). Taken together, these observations have led to the concept that AML is, in fact, a heterogeneous disease with its variants best defined by their molecular defects. Whereas in previous clinical trials of standard chemotherapy, or of allogeneic and autologous transplantation, patients were often treated as a homogeneous group, recent studies have refined the way patients are allocated to various treatments as well as the analysis of the results.

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References

  1. Stein AS, Forman SJ. Autologous hematopoietic cell transplantation for acute myeloid leukemia. In: Hematopoietic Cell Transplantation, 2nd ed. (Forman SJ, Blume KG, Thomas ED, eds.), London: Blackwell Science, 1999. pp. 963–977.

    Google Scholar 

  2. Caligiuri MA, Strout MP, Lawrence D, et al. Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics. Cancer Res 1998;58:55–59.

    PubMed  CAS  Google Scholar 

  3. Bloomfield CD, Lawrence D, Arthur DC, et al. Curative impact of intensification with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) varies by cytogenetic group. Blood 1994; 84:111.

    Google Scholar 

  4. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive post remission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 1994;331:896–903.

    Article  PubMed  CAS  Google Scholar 

  5. Dutcher JP, Schiffer CA, Wiernik PH. Hyperleukocytosis in adult acute nonlymphocytic leukemia: impact on remission rate and duration and survival. J Clin Oncol 1987;5:1364–1372.

    PubMed  CAS  Google Scholar 

  6. Brito-Babapulle F, Catovsky D, Galton DAG. Clinical and laboratory features of de novo acute myeloid leukemia with trilineage myelodysplasia. Br J Haematol 1987;66:445–450.

    Article  PubMed  CAS  Google Scholar 

  7. Goasguen JE, Matsuo T, Cox, et al. Evaluation of the dysmyelopoiesis in 336 patients with de novo acute myeloid leukemia. Major importance of dysgranulopoiesis for remission and survival. Leukemia 1992;6:520–525.

    PubMed  CAS  Google Scholar 

  8. Kuriyama K, Tomonaga M, Matsuo T, et al. Poor response to intensive chemotherapy in de novo myeloid leukemia with trilineage myelodysplasia. Br J Haematol 1994;86:767–773.

    Article  PubMed  CAS  Google Scholar 

  9. Geller RB, Zahurak M, Hurwit CA, et al. Prognostic importance of immunophenotyping in adults with acute myelocytic leukemia: The significance of the stem-cell glycoprotein CD34 (My 10). Br J Haematol 1990;76:340–347.

    Article  PubMed  CAS  Google Scholar 

  10. List AF. Role of multidrug resistance and its pharmacologic modulation in acute myeloid leukemia. Leukemia 1996;10:937–942.

    PubMed  CAS  Google Scholar 

  11. Willman CL, Kopecky K, Weick J, et al. Biologic parameters that predict treatment response in de novo acute myeloid leukemia: CD34, but not multidrug resistant (MDR) gene expression, is associated with a decreased complete remission rate and CD34 patients more frequently achieved CR with high-dose cytosine arabinoside. Proc ASCO 1992;11:262a.

    Google Scholar 

  12. Leith CP, Chen IM, Kopecky KJ, et al. Correlation of multidrug resistance (MDR) protein expression with functional dye/drug efflux in acute myeloid leukemia by multiparameter flow cytometry: identification of discordant CD34+/MDR1/Efflux+ and MDR1+/Efflux cases. Blood 1995;86:2329–2342.

    PubMed  CAS  Google Scholar 

  13. Leith CP, Kopecky KJ, Godwin JE, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDRI) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 1997;89:3323–3329.

    PubMed  CAS  Google Scholar 

  14. Saunders MJ, Tobal K, Liu Yin JA. Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation. Leuk Res 1994;18:891–895.

    Article  PubMed  CAS  Google Scholar 

  15. O’Brien S, Kantarjian HM, Keating MJ, 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 

  16. Nucifora G, Larson RA, Rowley RD. Persistence of the 8;21 translocation in patients with acute myeloid leukemia type M2 in long term remission. Blood 1993;82:712–715.

    PubMed  CAS  Google Scholar 

  17. Laczika K, Novak M, Hilgarth B, et al. Competitive CBFbeta/ MYH 11 reverse-transcription polymerase chain reaction for quantitative assessment of minimal residual disease during postremission therapy in acute myeloid leukemia with inversion (16): a pilot study. J Clin Oncol 1998;16:1519–1525.

    PubMed  CAS  Google Scholar 

  18. Evans PAS, Short MA, Jack AS, et al. Detection and quantitation of the CBFβ/MYH 11 transcripts associated with the inv(16) in presentation and follow-up samples from patients with AML. Leukemia 1997;11:364–369.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang FF, Murata-Collins JL, Gaytan P, et al. Twenty-four color spectral karyotyping reveals chromosome aberrations in cytogenetically normal acute myeloid leukemia. Genes Chromosomes Cancer 2000;28:318–328.

    Article  PubMed  CAS  Google Scholar 

  20. Golub TR, Slonim DK, Tamayo P, et al. Molecular classification of cancer: class discovery and class pr gene expression monitoring. Science 1999;286:531–537.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    PubMed  CAS  Google Scholar 

  22. Buchner T, Hiddemann W, Wormann B, et al. Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group. Blood 1999;93:4116–4124.

    PubMed  CAS  Google Scholar 

  23. Bishop JF, Matthews JP, Young G, Bradstock K, Lowenthal RM. 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 Lymphoma 1998;28:315–327.

    PubMed  CAS  Google Scholar 

  24. Weick JK, Kopecky KJ, Appelbaum FR, et al. 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 1996;88:2841–2851.

    PubMed  CAS  Google Scholar 

  25. Stein AS, O’Donnell MR, Slovak ML, et al. High-dose cytosine arabinoside and daunorubicin induction therapy for adult patients with de novo non M3 acute myelogenous leukemia: impact of cytogenetics on achieving a complete remission. Leukemia 2000;14:1191–1196.

    Article  PubMed  CAS  Google Scholar 

  26. Leith CP, Kopecky KJ, Ming Chen I, et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-Glycoprotein, MRP1 and LRP in acute myeloid leukemia. A Southwest Oncology Group study. Blood 1999;94:1086–1098.

    PubMed  CAS  Google Scholar 

  27. 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.

    PubMed  CAS  Google Scholar 

  28. Burnett AK, Goldstone AH, Stevens RMF, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukemia in first remission. Results of MRC AML 10 trial. Lancet 1998;351:700–708.

    Article  PubMed  CAS  Google Scholar 

  29. Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med 1995; 332:217–223.

    Article  PubMed  CAS  Google Scholar 

  30. Cassileth PA, Harrington DP, Appelbaum FR, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 1998;339:1649–1656.

    Article  PubMed  CAS  Google Scholar 

  31. Harrousseau J-L, Chan J-Y, Pignon B, et al. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. Blood 1997;90:2978–2986.

    Google Scholar 

  32. Ball ED, Mills LE, Cornwell GG 3rd, et al. Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow. Blood 1990;75:1199–1206.

    PubMed  CAS  Google Scholar 

  33. Cassileth PA, Andersen J, Lazarus HM, et al. Autologous bone marrow transplant in acute myeloid leukemia in first remission. J Clin Oncol 1993;11:314–319.

    PubMed  CAS  Google Scholar 

  34. Lowenberg B, Verdonck LJ, Dekker AW, et al. Autologous bone marrow transplantation in acute myeloid leukemia in first remission: results of a Dutch prospective study. J Clin Oncol 1990;8: 287–294.

    PubMed  CAS  Google Scholar 

  35. Burnett AK, Pendry K, Rawlinson PM, et al. Autograft to eliminate minimal residual disease in AML in first remission-update on the Glasgow experience. Bone Marrow Transplant 1990;6:59–60.

    PubMed  Google Scholar 

  36. Gorin NC, Aegerter P, Auvert B, et al. Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging. Blood 1990; 75:1606–1614.

    PubMed  CAS  Google Scholar 

  37. Stein AS, O’Donnell MR, Chai A, et al. In vivo purging with highdose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission. J Clin Oncol 1996; 14:2206–2216.

    PubMed  CAS  Google Scholar 

  38. Wheatly K, Burnett AK, Goldstone AH, et al. A simple, robust, validated and highly predictive index for the determination of riskdirected therapy in acute myeloid leukemia derived from the MRC AML 10 trial. Br J Haematol 1999;107:69–79.

    Article  Google Scholar 

  39. Fefer A. Graft-versus-tumor responses. In: Hematopoietic Cell Transplantation, 2nd ed. (Forman SJ, Blume KG, Thomas ED, eds.) London: Blackwell Science, 1999. pp.316–326.

    Google Scholar 

  40. Weisdorf DJ, Anderson PM, Kersey JH, Ramsay NKC. Interleukin2 therapy immediately after autologous marrow transplantation: toxicity, T cell activation and engraftment. Blood 1991;78:226.

    Google Scholar 

  41. Klingemann HG, Eaves CJ, Barnett MJ, et al. Transplantation of patients with high risk acute myeloid leukemia in first remission with autologous marrow cultured in interleukin-2 followed by interleukin-2 administration. Bone Marrow Transplant 1994; 14:389–396.

    PubMed  CAS  Google Scholar 

  42. Robinson N, Benyunes MC, Thompson JA, et al. Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study. Bone Marrow Transplant 1997;19:435–442.

    Article  PubMed  CAS  Google Scholar 

  43. Stein AS, O’Donnell MR, Slovak ML, et al. Immunotherapy with IL-2 after autologous stem cell transplant for acute myelogenous leukemia in first remission. In: Proceedings of the Tenth International Symposium on Autologous Blood and Marrow Transplantation, 2001. pp.450–459.

    Google Scholar 

  44. Thomas ED, Buckner CD, Clift RA, et al. Bone marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med 1979;301:597–599.

    Article  PubMed  CAS  Google Scholar 

  45. Appelbaum FR, Dahlberg S, Thomas ED, et al. Bone marrow transplantation or chemotherapy after remission induction for adults with acute nonlymphoblastic leukemia: a prospective comparison. Ann Intern Med 1984;101:581–588.

    PubMed  CAS  Google Scholar 

  46. Champlin RE, Ho WG, Gale RP, et al. Treatment of acute myelogenous leukemia: a prospective controlled trial of bone marrow transplantation versus consolidation chemotherapy. Ann Intern Med 1985;102:285–291.

    PubMed  CAS  Google Scholar 

  47. Stockerl-Goldstein KE, Blume KG. Allogeneic hematopoietic cell transplantation for adult patients with acute myeloid leukemia. In: Hematopoietic Cell Transplantation, 2nd ed. (Forman SJ, Blume KG, Thomas ED, eds.) London: Blackwell Science, 1999. pp. 823–834.

    Google Scholar 

  48. Cahn JY, Labopin M, Mandelli F, et al. Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years. A retrospective analysis of the European bone marrow transplant group. Blood 1995;85:575–579.

    PubMed  CAS  Google Scholar 

  49. Baker JP, Detsky AS, Wesson DE, et al. Nutritional assessment: a comparison of clinical judgement and objective measurements. N Engl J Med 1982;306:969–972.

    Article  PubMed  CAS  Google Scholar 

  50. Fung H, Jamieson C, Snyder D, et al. Allogeneic bone marrow transplantation (BMT) for AML in first remission (1CR) utilizing fractionated total body irradiation (FTBI) and allogeneic bone marrow transplantation for bcr-abl positive acute lymphoblastic leukemia. VP-16: analysis of risk factors for relapse and diseasefree survival. Blood 1999;94:167a.

    Google Scholar 

  51. Estey EH. Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia 2000;14:476–479.

    Article  PubMed  CAS  Google Scholar 

  52. List AF, Spier C, Greer J, et al. Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J Clin Oncol 1993;11:1652–1660.

    PubMed  CAS  Google Scholar 

  53. List AF, Kopecky KJ, Willman CL, et al. Benefit of cyclosporine (CsA) modulation of anthracycline resistance in high-risk AML: a Southwest Oncology Group (SWOG) study. Blood 1998;92:312a.

    Google Scholar 

  54. Collins RH Jr, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997;15:433–444.

    PubMed  Google Scholar 

  55. Porter DL, Roth MS, Lee SJ, et al. Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1996;18:975–980.

    PubMed  CAS  Google Scholar 

  56. Sievers EL, Appelbaum FR, Spielberger RT, et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamycin immunoconjugate. Blood 1999;93:3678–3684.

    PubMed  CAS  Google Scholar 

  57. Leopold LH, Berger MS, Cheng S-C, Estey E. Comparative efficacy and safety of gemtuzumab ozogamicin monotherapy and highdose cytarabine combination therapy in the treatment of patients with acute myeloid leukemia in first relapse. Blood 2000;96:504a.

    Google Scholar 

  58. Löwenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the EORTC Leukemia Group. J Clin Oncol 1989:1:1268–1274.

    Google Scholar 

  59. Rowe JM, Andersen J, Mazza JJ, et al. A randomized placebocontrolled study of granulocyte-macrophage colony-stimulating factor in adult patients (>55–70 years of age) with acute myeloid myelogenous leukemia (AML): a study of the Eastern Cooperative Oncology Group (E1490). Blood 1995;86:457–462.

    PubMed  CAS  Google Scholar 

  60. Lancet JE, Willman CL, Bennett JM. Acute myelogenous leukemia and aging. Clinical interactions. In: Hematology/Oncology Clinics of North America. (Balducci L, Extermann M, guest eds.), Philadelphia: WB Saunders, 2000. pp. 251–267.

    Google Scholar 

  61. Godwin JE, Kopecky KJ, Head DR, et al. A double-blind placebocontrolled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study (9031). Blood 1998;91:3607–3615.

    PubMed  CAS  Google Scholar 

  62. Cahn JY, Labopin M, Mandelli F, et al. Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group. Blood 1995;85:575–579.

    PubMed  CAS  Google Scholar 

  63. Storb, R, Yu, C, McSweeney P. Mixed chimerism after transplantation of allogeneic hematopoietic cells. In: Hematopoietic Cell Transplantation, 2nd ed. (Forman SJ, Blume KG, Thomas ED, eds.) London: Blackwell Science, 1999. pp. 287–295.

    Google Scholar 

  64. Champlin R, Khouri I, Kornblau S, et al. Allogeneic hematopoietic transplantation as adoptive immunotherapy. In: Hematology/ Oncology Clinics of North America, (Schiller GJ, guest ed.) Philadelphia: WB Saunders Company, 1999. pp. 1041–1057.

    Google Scholar 

  65. Appelbaum FR. Radioimmunotherapy and hematopoietic cell transplantation. In: Hematopoietic Cell Transplantation, 2nd ed. (Forman SJ, Blume KG, Thomas ED, eds.) London: Blackwell Science, 1999. pp. 168–175.

    Google Scholar 

  66. Bensinger W, Martin P, Storer B, et al. Transplantation of bone marrow as compared with peripheral blood cells from HLA-identical relatives in patients with hematologic malignancies. N Engl J Med 2001;344:175–181.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Ricardo T. Spielberger
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  2. Stephen J. Forman
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Editors and Affiliations

  1. St. Jude Children’s Research Hospital, University of Tennessee Health Science Center, Memphis, TN, USA

    Ching-Hon Pui MD

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Spielberger, R.T., Forman, S.J. (2003). Treatment of Adult Acute Myelogenous Leukemia. In: Pui, CH. (eds) Treatment of Acute Leukemias. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-307-1_20

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  • DOI: https://doi.org/10.1007/978-1-59259-307-1_20

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-212-4

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