Intensified Daunorubicin in Induction Therapy and Autologous Peripheral Blood Stem Cell Transplantation in Postremission Therapy (Double-7 Protocol) for Adult Acute Myeloid Leukemia

  • Noriko Usui
  • Nobuaki Dobashi
  • Osamu Asai
  • Shingo Yano
  • Yuichi Yahagi
  • Takeshi Saito
  • Yuko Yamaguchi
  • Kinuyo Kasama
  • Yutaka Okawa
  • Naohiro Sekiguchi
  • Yutaka Takei
  • Katsuki Sugiyama
  • Yoji Ogasawara
  • Hiroko Ohtsubo
  • Ken Kaito
  • Masayuki Kobayashi
Progress in hematology

Abstract

To investigate whether an intensified dose of daunorubicin (DNR) in induction therapy and autologous peripheral blood stem cell transplantation (PBSCT) in the postremission period are effective treatments, we used a Double-7 protocol to treat adult patients with de novo acute myeloid leukemia (excluding M0 and M3). Induction therapy consisted of 40 mg/m2 of DNR intravenous drip infusion for 7 days and 200 mg/m2 of ara-C by continuous infusion for 7 days (7 + 7 DC regimen). Patients who achieved complete remission (CR) were given high-dose chemotherapy with autologous PBSCT in postremission therapy. Of the 22 assessable patients, 16 attained CR (73%). Disease-free survival (DFS) and overall survival (OS) at 3 years were 61.2% and 48.1%, respectively. Nine of the CR patients underwent PBSCT without therapy-related mortality. Patients in a favorable cytogenetic group (n = 7) attained 100% CR and long-term survival (71.4% DFS and 85.7% OS at 3 years). Thus, intensified DNR administration of 280 mg/m2 (40 mg/m2 per day for 7 days) in induction therapy for adult patients younger than 60 years of age might be optimal or at least comparable with the new anthracyclines such as idarubicin. In addition, autologous PBSCT in postremission therapy might improve DFS and OS, at least for patients in a favorable cytogenetic group, such as those with a t(8;21) abnormality.Int J Hematol. 2002; 76: 436-445.

Key words

Adult AML Daunorubicin Induction therapy Auto-PBSCT Double-7 

References

  1. 1.
    Appelbaum F, Rowe JM, Radich J, Dick JE. Acute myeloid leukemia.Hematology (Am Soc Hematol Educ Program). 2001: 62-86.Google Scholar
  2. 2.
    Lowenberg B, Downing J, Burnett A. Acute myeloid leukemia.N Engl J Med. 1999; 341: 1051–1062.PubMedCrossRefGoogle Scholar
  3. 3.
    Brenner M, Pinkel D. Cure of leukemia.Semin Hematol. 1999; 36: 73–83.PubMedGoogle Scholar
  4. 4.
    Bishop JF. The treatment of adult acute myeloid leukemia.Semin Oncol. 1997; 24: 57–69.PubMedGoogle Scholar
  5. 5.
    Ohno R. How high can we increase complete remission rate in adult acute myeloid leukemia?Int J Hematol. 2000; 72: 272–279.PubMedGoogle Scholar
  6. 6.
    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
  7. 7.
    Bishop JF, Lowenthal RM, Josuna D, et al. Etoposide in acute non-lymphocytic leukemia.Blood. 1990; 75: 27–32.PubMedGoogle Scholar
  8. 8.
    Yates J, Glidewell P, Wiemik P, et al. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study.Blood. 1982; 60: 454–462.PubMedGoogle Scholar
  9. 9.
    Bermann E, Heller G, Santorsa J, et al. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia.Blood. 1991; 77: 1666–1674.Google Scholar
  10. 10.
    Vogler WR, Velez-Garcia E, Weiner RS, et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.J Clin Oncol. 1992; 10: 1103–1111.PubMedGoogle Scholar
  11. 11.
    Wiernik P, Banks PL, Case DC Jr, et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia.Blood. 1992; 79: 313–319.PubMedGoogle Scholar
  12. 12.
    Hansen OP, Pedersen-Bjergaard J, Ellegaard J, et al. Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial: the Danish Society of Hematology Study Group on AML, Denmark.Leukemia. 1991; 5: 510–516.PubMedGoogle Scholar
  13. 13.
    Arlin Z, Case D, Moore J, et al. Randomized multicenter trial of cytosinearabinoside with mitoxantrone or daunorubicin in previously untreated patients with acute nonlymphocytic leukemia (ANLL): Lederle Cooperative Group.Leukemia. 1990; 4: 177–183.PubMedGoogle Scholar
  14. 14.
    Usui N, Dobashi N, Kobayashi T, et al. Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.J Clin Oncol. 1998; 16: 2086–2092.PubMedGoogle Scholar
  15. 15.
    Creutzig U, Ritter J, Zimmermann M, et al. Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93: AML-BFM Study Group.Leukemia. 2001; 15: 348–354.PubMedCrossRefGoogle Scholar
  16. 16.
    Champlin R, Gajewski J, Nimer S, et al. Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high dose cytarabine and daunorubicin consolidation treatment.J Clin Oncol. 1990; 8: 1199–1206.PubMedGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    Kern W, Aul C, Maschmeyer G, et al. Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison.Leukemia. 1998; 12: 1049–1055.PubMedCrossRefGoogle Scholar
  19. 19.
    Bloomfield C, Lawrence D, Byrd JC, et al. Frequency prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.Cancer Res. 1998; 58: 4173–4179.PubMedGoogle Scholar
  20. 20.
    Byrd J, 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.PubMedGoogle Scholar
  21. 21.
    Zittoun R, 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 delľAdulto (GIMEMA) Leukemia Cooperative Groups.N Engl J Med. 1995; 332: 217–223.PubMedCrossRefGoogle Scholar
  22. 22.
    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.Blood. 1997; 90: 2978–2986.PubMedGoogle Scholar
  23. 23.
    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: 1649–1659.PubMedCrossRefGoogle Scholar
  24. 24.
    Burnett AK, Goldstone AH, Stevens RM, 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: UK Medical Research Council Adult and Children’s Leukaemia Working Parties.Lancet. 1998; 351: 700–708.PubMedCrossRefGoogle Scholar
  25. 25.
    Pavlovsky S, Fernandez I, Milone G, et al. Autologous peripheral blood progenitor cell transplantation mobilized with high-dose cytarabine in acute myeloid leukemia in first complete remission.Ann Oncol. 1998; 9: 151–157.PubMedCrossRefGoogle Scholar
  26. 26.
    Gorin NC. Autologous stem cell transplantation in acute myeloid leukemia.Blood. 1998; 92: 1073–1090.PubMedGoogle Scholar
  27. 27.
    Bennett JM, Catovsky D, Daniel MT, et al. Proposal for the classification of the acute leukaemias French-American-British (FAB) co-operative group.Br J Haematol. 1976; 33: 451–458.PubMedCrossRefGoogle Scholar
  28. 28.
    Bennett JM, Catovsky D, Daniel MT, et al. Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-M0).Br J Haematol. 1991; 78: 325–329.PubMedCrossRefGoogle Scholar
  29. 29.
    Usui N, Dobashi N, Asai O, et al. Sequential administration of mitoxantrone and etoposide for adult acute myeloid leukemia [abstract].Proc Am Soc Clin Oncol. 2000; 19: 33a.Google Scholar
  30. 30.
    Cheson BD, Cassileth PA, Head DR, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia.J Clin Oncol. 1990; 8: 813–819.PubMedGoogle Scholar
  31. 31.
    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.Blood. 1998; 92: 2322–2333.PubMedGoogle Scholar
  32. 32.
    Slovak M, 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.PubMedGoogle Scholar
  33. 33.
    National Cancer Institute.Common Toxicity Criteria. Bethesda, MD: National Cancer Institute; 1999: 1–80.Google Scholar
  34. 34.
    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations.J Am Stat Assoc. 1958; 53: 457–481.CrossRefGoogle Scholar
  35. 35.
    Dixon D, Simon R. Sample size considerations for studies comparing survival curves using historical controls.J Clin Epidemiol. 1998; 41: 1209–1213.CrossRefGoogle Scholar
  36. 36.
    Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient, II: analysis and examples.Br J Cancer. 1977; 35: 1–39.PubMedGoogle Scholar
  37. 37.
    Rowe J, Tallman M. Intensifying induction therapy in acute myeloid leukemia: has a new standard of care emerged?Blood. 1997; 90: 2121–2126.PubMedGoogle Scholar
  38. 38.
    Rowe JM. What is the best induction regimen for acute myelogenous leukemia?Leukemia. 1998; 12(suppl): S16-S19.PubMedGoogle Scholar
  39. 39.
    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: 3888–3895.PubMedCrossRefGoogle Scholar
  40. 40.
    Kobayashi T, Miyawaki S, Tanimoto M, et al. Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia.J Clin Oncol. 1996; 14: 204–213.PubMedGoogle Scholar
  41. 41.
    Cassileth PA, Lynch E, Hines JD, et al. Varying intensity of postremission therapy in acute myeloid leukemia.Blood. 1992; 79: 1924–1930.PubMedGoogle Scholar
  42. 42.
    Hewlett J, Kopecky KJ, Head D, et al. A prospective evaluation of the role of allogeneic marrow transplantation and low-dose monthly maintenance chemotherapy in the treatment of adult acute myelogenous leukemia (AML): a Southwest Oncology Group study.Leukemia. 1995; 9: 562–569.PubMedGoogle Scholar
  43. 43.
    Miyawaki S, Tanimoto M, Kobayashi T, et al. No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of acute myeloid leukemia: the JALSG-AML 92 study: Japan Adult Leukemia Study Group.Int J Hematol. 1999; 70: 97–104.PubMedGoogle Scholar
  44. 44.
    Sievers E, Larson RA, Stadtmauer EA, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.J Clin Oncol. 2001; 19: 3244–3254.PubMedGoogle Scholar
  45. 45.
    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.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Noriko Usui
    • 1
  • Nobuaki Dobashi
    • 1
  • Osamu Asai
    • 1
  • Shingo Yano
    • 1
  • Yuichi Yahagi
    • 1
  • Takeshi Saito
    • 1
  • Yuko Yamaguchi
    • 1
  • Kinuyo Kasama
    • 1
  • Yutaka Okawa
    • 1
  • Naohiro Sekiguchi
    • 1
  • Yutaka Takei
    • 1
  • Katsuki Sugiyama
    • 1
  • Yoji Ogasawara
    • 1
  • Hiroko Ohtsubo
    • 1
  • Ken Kaito
    • 1
  • Masayuki Kobayashi
    • 1
  1. 1.Division of Hematology and Oncology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan

Personalised recommendations