International Journal of Hematology-Oncology and Stem Cell Research 2004. 1(1):6-11.

Acute Myeloid Leukemia (AML): The Role of Maintenance Chemo¬therapy
Thomas Büchner, Wolfgang Hiddemann, Wolfgang E Berdel, Bernhard Wörmann, Helmut Löffler, Claudia Schoch, Torsten Haferlach, Wolf-Dieter Ludwig, Georg Maschmeyer, Eva Lengelder, Peter Staib, Reinhard Andreesen, Leopold Balleisen, Detlef Haase, Hartmut Eimermacher, Carlo Aul, Herbert Rasche, Jens Uhlig, Andreas Grüneisen, Hans Edgar Reis, Joachim Hartlapp, Wolf-Dietrich Hirschmann, Hans-Josef Weh, Hermann-Josef Pielken, Winfried Gassmann, Andrea Schumacher, Maria-Cristina Sauerland, Achim Heinecke

Abstract


Maintenance treatment for patients with acute myeloid leukemia (AML) in remission has recently been controversially discussed and even abandoned by several groups. An analysis of 16 published multicenter trials, however, revealed the highest probabilities of relapse free survival (RFS) in the range of 35-42 % at 4-5 years only in patients assigned to maintenance treatment when adult age and intent-to-treat conditions were considered. After having demonstrated a superior RFS from 3 year maintenance following standard dose consolidation over that from consolidation alone (p<0.0001), the German AMLCG requestioned the effect of maintenance randomly compared with sequential high-dose AraC and Mitoxantrone (S-HAM) in patients having received intensified induction treatment. The RFS shows an advantage for maintenance with 32 % versus 25 % (p= .021). We conclude that maintenance treatment continues to substantially contribute to the management of adult patients with AML, even as part of recent strategies using intensified induction treatment, and thus appears necessary in these settings.

Keywords


Acute myeloid leukemia; maintenance therapy

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References


- Burnett AK, Kell J, Rowntree C. Role of allogeneic and autologous hematopoietic stem cell transplantata- tion in acute myeloid leukemia. Int J Hematol 2000;72;280-284.

- Rai K, Holland J, Gildewell O et al. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood 1981;58:1203-1212.

- Büchner T, Hiddemann W, Wörmann B et al. Hematopoietic growth factors in acute myeloid leukemia: supportive and priming effects. Sem Oncol 1998;24:124-131.

- 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;3:1583-1589.

- Preisler H, Davis R, Kirshner J et al. Comparison of three remission induction regimens and two postinduc- tion strategies for the treatment of acute nonlympho- cytic leukemia: a Cancer and Leukemia B Group study. Blood 1987;69:1441-1449.

- Bishop J, Lowenthal R, Joshua D et al. Etoposide in acute nonlymphocytic leukemia. Blood 1990;75:27-32.

- Dillmann R, Davis R, Green M 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.

- Cassileth P, Lynch E, Hines J et al. Varying intensity of postremission therapy in acute myeloid leukemia. Blood 1992;79:1924-1930.

- Ohno R, Kobayashi T, Tanimoto M et al. Random- ized study of individualized induction therapy with of without Vincristine, and of maintenance – intensifica- tion therapy between 4 or 12 courses in adult acute myeloid leukemia. Cancer 1993;71:3888-3895.

- Mayer R, Davis R, Schiffer C et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 1994;331:896-942.

- Zittoun R, 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.

- Rees J, Gray R, Weathly K. Dose intensification in acute myeloid leukemia: greater effectiveness at lower cost. Principal report of the Medical Research Councils’s AML9 study. Br J Haematol 1996;94:89- 98.

- Kobayashi T, Miyawaki S, Tanimoto M et al. Randomized trials between Behenoyl cytarabine and IJHOBMT vol.1, No.1; 2004/ 10 cytarabine in combination induction and consolidation therapy, and with or without Ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. JCO 1996;14:204-213.

- Bishop J., Matthews J, Young G et al. A random- ized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 1996;87:1710-1717.

- Weick J, Kopecky K, Appelbaum F 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.

- Porwit-MacDonald A, Janossy G, Ivory K et al. Leukemia-associated changes identified by quantitative flow cytometry. IV. CD34 overexpression in acute myelogenous leukemia M2 with t(8;21). Blood 1996;87:1162-1169.

- Hann I, Stevens R, Goldstone A et al. 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). Blood 1997;89:2311-2318.

- Burnett A, Goldstone A, Stevens R et al. Randomized comparison of addition of autologous bone-marrow transplantation to intensive chemother- apy for acute myeloid leukemia in first remission: results of MRC AML10 trial. Lancet 1998;351:700- 708.

- Löwenberg G, Suciu S, Archimbaud E et al. Mitoxantrone versus daunorubicin in induction- consolidation chemotherapy – the value of low-dose cytarabine for maintenance of remission, and n 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

- Cassileth P, Harrington D., Appelbaum F 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.

- Büchner T, Hiddemann W, Wörmann 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.

- Büchner T, Urbanitz D, Rühl H et al. Role of chemotherapy for AML in remission. Lancet 1985;25:1224

- Hiddemann W, Kreutzmann H, Straif K et al. High-dose cytosine arabinoside and mitoxantrone: A highly effective regimen in refractory acute myeloid leukemia. Blood 97;69:744-749.

- Kern W, Schleyer E, Unterhalt M, Wörmann B, Büchner T, Hiddemann W. High antileukemic activity of sequential high dose cytosine arabinoside and mitoxantrone in patients with refractory acute leukemias. Cancer 1997;79:59-68.

- Th. Büchner, W. Hiddemann, W.E. Berdel, B. Requestioning the role of prolonged maintenance chemotherapy in AML: randomized trial by the German AML Cooperative Group. Blood 2001;98 Suppl 1:1933

- Aaronson NK, Ahmedzai S, Bergman B et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365-376, 1993

- Schumacher A, Kessler T, Büchner T, et al. Quality of life in adult patients with acute myeloid leukemia receiving intensive and prolonged chemotherapy – a longitudinal study. Leukemia 12:586-592, 1998

- Schumacher A, Wewers D, Heinecke A, et al. Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia. Leukemia Research 26:355-362


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