Current Hematologic Malignancy Reports

, Volume 1, Issue 2, pp 108–113

Chemotherapy for patients with acute myeloid leukemia in first remission

Article

Abstract

Although the majority of patients with acute myeloid leukemia (AML) achieve a complete remission with induction chemotherapy, most will ultimately relapse. Therefore, the optimal postremission therapy for AML remains to be defined, and further improvements in treatment strategies are required. Clinical trials have demonstrated that early intensive consolidation therapy with high-dose cytarabine can produce prolonged responses in up to 40% of patients in remission after standard induction therapy. Equally, however, it has been shown that high-dose cytarabine used in induction therapy can deliver equivalent long-term results. Autologous and allogeneic stem cell transplantation in first remission are also valid alternatives, but the value of low-dose maintenance treatment seems confined to acute promyelocytic leukemia. Further improvement in the treatment of AML is likely to depend on the development of new strategies, such as molecularly targeted or immune therapies.

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References and Recommended Reading

  1. 1.
    Bloomfield CD, Shuma C, Regal L, et al.: Long-term survival of patients with acute myeloid leukemia. A third follow-up of the Fourth International Workshop on Chromosomes in Leukemia. Cancer 1997, 80(11 Suppl):2191–2198.PubMedCrossRefGoogle Scholar
  2. 2.
    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.PubMedGoogle Scholar
  3. 3.
    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, 78:2520–2526.PubMedGoogle Scholar
  4. 4.
    Bishop J, Lowenthal R, Joshua D, et al.: Australian Leukaemia Study Group: Etoposide in acute non-lymphocytic leukaemia. Blood 1990, 75:27–32.PubMedGoogle Scholar
  5. 5.
    Bishop JF, Matthews JP, Young GAR, et al.: A randomized trial of high dose cytarabine in induction in acute myeloid leukemia. Blood 1996, 87:1710–1717.PubMedGoogle Scholar
  6. 6.
    Kell WJ, Burnett AK, Chopra R, et al.: A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. Blood 2003, 102:4277–4283.PubMedCrossRefGoogle Scholar
  7. 7.
    Gilliland DG, Griffin JD: The roles of FLT3 in hematopoiesis and leukemia. Blood 2002, 100:1532–1542.PubMedCrossRefGoogle Scholar
  8. 8.
    Cassileth PA, Harrington DP, Hines JD, et al.: Maintenance chemotherapy prolongs remission duration in acute non-lymphocytic leukemia. J Clin Oncol 1988, 6:583–587.PubMedGoogle Scholar
  9. 9.
    Cassileth PA, Begg CB, Bennett JM, et al.: A randomized study of the efficacy of consolidation therapy in adult acute non-lymphocytic leukemia. Blood 1984, 63:843–847.PubMedGoogle Scholar
  10. 10.
    Mayer RJ, Davis RB, Schiffer CA, et al.: Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 1994, 331:896–903. Landmark paper describing the benefit of high-dose cytarabine in consolidation therapy.PubMedCrossRefGoogle Scholar
  11. 11.
    Cassileth PA, Lynch E, Hines JD, et al.: Varying intensity of post-remission therapy in acute myeloid leukemia. Blood 1992, 79:1924–1930.PubMedGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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. Study confirming the unique importance of high-dose cytarabine in consolidation therapy.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedGoogle Scholar
  15. 15.
    Farag SS, Ruppert AS, Mrozek K, et al.: Outcome of induction and post-remission therapy in younger adults with acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol 2005, 23:482–493.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    Bradstock KF, Matthews JP, Lowenthal RM, et al.: A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood 2005, 105:481–488. Trial prospectively examining the value of high-dose cytarabine in consolidation after intensive induction chemotherapy.PubMedCrossRefGoogle Scholar
  18. 18.
    Burnett AK, Goldstone AH, Stevens RMF, et al.: Randomized comparison of addition of autologous bone marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet 1998, 351:700–708.PubMedCrossRefGoogle Scholar
  19. 19.
    Harousseau J-L, Cahn J-Y, Pignon B, et al.: Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. Groupe Ouest-Est des Leuc’emies Aiguës Myeloblastiques. Blood 1997, 90:2978–2986.PubMedGoogle Scholar
  20. 20.
    Zittoun RA, Mandelli F, Willemze R, et al.: Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med 1995, 332:217–223.PubMedCrossRefGoogle Scholar
  21. 21.
    Collison EA, Lashkari A, Malone R, et al.: Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission. Leukemia 2003, 17:2183–2188.CrossRefGoogle Scholar
  22. 22.
    Gorin NC, Labopin M, Meloni G, et al.: Autologous bone marrow transplantation for acute myeloblastic leukemia in Europe: further evidence for the role of marrow purging by mafosfamide. Leukemia 1991, 5:896–904.PubMedGoogle Scholar
  23. 23.
    Linker CA, Ries CA, Damon LE, et al.: Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a conditioning regimen. Blood 1993, 81:311–318.PubMedGoogle Scholar
  24. 24.
    Burnett AK, Wheatley K, Goldstone AH, et al.: Medical Research Council Adult and Paediatric Working Parties: The value of allogeneic bone marrow transplant in patients with acute myeloid leukemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002, 118:385–400. Analysis of the impact of allogeneic transplantation in first complete remission in a large patient cohort.PubMedCrossRefGoogle Scholar
  25. 25.
    Giralt S, Estey E, Albitar M, et al.: Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1998, 91:756–763.Google Scholar
  26. 26.
    Mohty M, de Lavallade H, Ladaique P, et al.: The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison. Leukemia 2005, 19:916–920.PubMedCrossRefGoogle Scholar
  27. 27.
    Buchner T, Urbanitz D, Hiddemann W, et al.: Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group. J Clin Oncol 1985, 3:1583–1589.PubMedGoogle Scholar
  28. 28.
    Preisler HD, Davis RB, Kirschner J, et al.: Comparison of three remission induction regimens and two post-induction strategies for the treatment of acute nonlymphocytic leukemia. A Cancer and Leukemia Group B study. Blood 1987, 69:1441–1449.PubMedGoogle Scholar
  29. 29.
    Buchner T, Hiddemann W, Berdel WE, et al.: 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia: a randomized trial of the German AML Cooperative Group. J Clin Oncology 2003, 21:4496–4504.CrossRefGoogle Scholar
  30. 30.
    Brune M, Castaigne S, Catalano J, et al.: Improved leukemiafree survival after post-consolidation treatment with histamine dihydrochloride and interleukin-2 in AML: a randomized phase III trial [abstract]. Blood 2004, 104:Abstract 261.Google Scholar
  31. 31.
    Fenaux P, Chastang C, Chevret S, et al. for the European APL Group: A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance chemotherapy in newly diagnosed acute promyelocytic leukemia. Blood 1999, 94:1192–1200. Trial that established the role for maintenance therapy in APL after ATRA-based induction.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.Blood and Marrow Transplant ServiceWestmead HospitalSydneyAustralia

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