Current Treatment Options in Oncology

, Volume 8, Issue 4, pp 296–304

Maintenance for Acute Myeloid Leukemia Revisited

  • Thomas Büchner
  • Utz Krug
  • Wolfgang E. Berdel
  • Achim Heinecke
  • Maria Cristina Sauerland
  • Bernhard Wörmann
  • Wolfgang Hiddemann
Acute Leukemia

Opinion Statement

Maintenance treatment for AML is an approach to minimize residual disease, optimize quality of remission and prevent a leukemic regrowth over a longer period of time. This intention implies a certain antileukemic activity and myelotoxicity. Thus, a prolonged myelosuppressive maintenance is best exemplified by the optimized protocol of the CALGB published by Kanti R. Rai in 1981 (Blood 58:1203–1212, 1981) and derived by the AMLCG as a therapeutic standard. From our today’s knowledge about the impact of various strategies, a lack of postremission therapy is not compatible with durable remissions. Even after an induction-type consolidation, the classic CALGB-type maintenance, or a comparably intensive regimen improved the relapse-free survival over that from alternatives. Some studies which failed to show a benefit used maintenance at low-dosage or short duration. Data about maintenance delivery in patients reaching long-term remissions demonstrate feasibility and compliance, and a low maintenance-related death rate can compete with that from alternative options. Revisiting maintenance, however, requires a comparison with other strategies on the basis of intention-to-treat. Either single prospective trials or crosstrial networking by a common standard arm and general upfront randomization can further assess the relative value of maintenance for AML.


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References and Recommended Reading

Papers of particular interest, published recently, has been highlighted as: •Of importance ••Of major importance

  1. 1.
    Tallman MS, Andersen JW, Schiffer C, et al.: All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997, 337: 1021–1028PubMedCrossRefGoogle Scholar
  2. 2.
    Dombret H. Fenaux P, Soignet SL, Tallman M.: Established practice in the treatment of patients with acute promyelocytic leukemia and the introduction of arsenic trioxide as a novel target. Sem Hematol 2002, 39: 8–13CrossRefGoogle Scholar
  3. 3.••
    Bloomfield CD, Lawrence D, Byrd J, et al.: Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Research 1998, 58: 4173–4179PubMedGoogle Scholar

Assessment of high-dose cytarabine intensification as postremission treatment according to cytogenetic groups.

  1. 4.
    Büchner T, Berdel WE, Schoch C, et al.: Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol 2006, 24: 2480–2489PubMedCrossRefGoogle Scholar
  2. 5.
    Taeuber CM.: Sixty-five plus in America, Current Population Reports, Special Studies, Rev. ed. Washington, DC: U.S. Government Printing Office; 1993:23–178, RVGoogle Scholar
  3. 6.
    National Cancer Institute: Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review 1975–2000Google Scholar
  4. 7.
    Burnett AK, Goldstone AH, Stevens RMF, et al.: Randomised 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: 700–708PubMedCrossRefGoogle Scholar
  5. 8.
    Burnett AK, Wheatley K, Goldstone AH, et al.: 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 2002, 118: 385–400PubMedCrossRefGoogle Scholar
  6. 9.
    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 myleoid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMA AML-10 trial. Blood 2003, 102: 1232–1240PubMedCrossRefGoogle Scholar
  7. 10.
    Cornelissen JJ, van Putten WLJ, Verdonck LF, et al.: 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 2007, 109: 3658–3666PubMedCrossRefGoogle Scholar
  8. 11.•
    •Rai KR, Holland JF, Glidewell OJ, et al.: Treatment of acute myelocytic Leukemia: A study by Cancer and Leukemia Group B. Blood 1981, 58: 1203–1212PubMedGoogle Scholar

Optimization and establishment of the classic prolonged monthly myelosuppressive maintenance for AML.

  1. 12.
    Büchner 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 (AML): a randomized trial of the German AML Cooperative Group. J Clin Oncol 2003, 21: 4496–4504PubMedCrossRefGoogle Scholar
  2. 13.
    Büchner 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: 1583–1589PubMedGoogle Scholar
  3. 14.
    Preisler H, Davis RB, Kirshner J, et al.: Comparison of three remission inducition regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: A Cancer and Leukemia Group B study. Blood 1987, 6: 1441–1449Google Scholar
  4. 15.
    Cassileth PA, Lynch E, Hines JD, et al.: Varying intensity of postremission therapy in acute myeloid leukemia. Blood 1992, 79: 1924–1930PubMedGoogle Scholar
  5. 16.
    Ohno R, Kobayashi T, Tanimoto M, et al.: Randomized study of individualized induction therapy with or without Vincristine, and of maintenance-intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. Cancer 1993, 71: 3888–3895PubMedCrossRefGoogle Scholar
  6. 17.•
    Löwenberg 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 of the Leukemia Cooperative Group of the European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative HOVON Group Randomized phase III study AML-9. J Clin Oncol 1998, 16: 872–881PubMedGoogle Scholar

Validation of low-dose araC for maintenance treatment in older patients with AML.

  1. 18.
    Stone R, Berg DT, George SL, et al.: Postremission therapy in older patients with de-novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine. Blood 2001, 98: 548–553PubMedCrossRefGoogle Scholar
  2. 19.
    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 AML 11 trial. Blood 2001, 8: 1302–1311CrossRefGoogle Scholar
  3. 20.
    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: 1649–1656PubMedCrossRefGoogle Scholar
  4. 21.•
    Büchner T, Döhner H, Ehninger G, et al.: Up-front randomization and common standard arm: a proposal for comparing AML treatment strategies between different studies. Leuk Res 2002, 26: 1073–1075PubMedCrossRefGoogle Scholar

Proposal of cross-trial networking to compare therapeutic strategies among separate clinical studies.

  1. 22.•
    Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 1994, 331: 896–942. Establishment of postremission therapy for AML by 4 courses of high-dose araCPubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2007

Authors and Affiliations

  • Thomas Büchner
    • 1
  • Utz Krug
    • 1
  • Wolfgang E. Berdel
    • 1
  • Achim Heinecke
    • 2
  • Maria Cristina Sauerland
    • 2
  • Bernhard Wörmann
    • 3
  • Wolfgang Hiddemann
    • 4
  1. 1.Department of Medicine, Hematology and OncologyUniversity of MünsterMunsterGermany
  2. 2.Department of Medical Informatics and BiomathematicsUniversity of MünsterMunsterGermany
  3. 3.Department of Hematology and OncologyMunicipal Medical CenterBraunschweigGermany
  4. 4.Department of Internal Medicine IIIUniversity of MunichMunichGermany

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