Annals of Hematology

, Volume 85, Issue 6, pp 357–365

Standard induction chemotherapy followed by attenuated consolidation in elderly patients with acute myeloid leukemia

  • Je-Hwan Lee
  • Seong-Jun Choi
  • Jung-Hee Lee
  • Jae-Hoo Park
  • Hawk Kim
  • Young-Don Joo
  • Won Sik Lee
  • Dae Young Zang
  • Hyo Jung Kim
  • Kyoo-Hyung Lee
  • Cooperative Study Group A for Hematology
Original Article


The benefits of intensive post-remission chemotherapy have not been verified in elderly patients with acute myeloid leukemia (AML). To reduce fatal complications caused by intensive post-remission therapy, we performed a prospective phase II multicenter trial of standard induction chemotherapy (‘7+3’ of cytarabine plus daunorubicin), followed by two cycles of attenuated consolidation therapy (‘5+1’ of cytarabine plus daunorubicin) for elderly patients with AML, excluding those with M3. Of the 41 patients enrolled in the study, 24 (58.5%) attained CR. Of these 24, 17 (70.8%) completed both planned cycles of consolidation therapy. After a median follow-up of 566 days (range, 63–1190 days) among surviving patients, 15 relapsed, with an actuarial 3-year disease-free survival rate of 22.5%. There were no fatal complications during consolidation therapy. Actuarial 3-year overall survival was 17.0%. These findings suggest that, when compared with previous findings using more intensive consolidation therapy, attenuated consolidation therapy does not compromise outcomes in elderly AML patients.


Elderly patients Acute myeloid leukemia Attenuated consolidation therapy 


  1. 1.
    Buchner T, Hiddemann W, Berdel W, Wormann B, Schoch C, Loffler H, Haferlach T, Schumacher A, Staib P, Balleisen L, Gruneisen A, Rasche H, Aul C, Heyll A, Lengfelder E, Ludwig WD, Maschmeyer G, Eimermacher H, Karow J, Frickhofen N, Hirschmann WD, Sauerland MC (2002) Acute myeloid leukemia: treatment over 60. Rev Clin Exp Hematol 6:46–59 (Discussion 86–87)PubMedCrossRefGoogle Scholar
  2. 2.
    Stone RM, O’Donnell MR, Sekeres MA (2004) Acute myeloid leukemia. Hematology (Am Soc Hematol Educ Program) 98–117Google Scholar
  3. 3.
    Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM, Head DR, Appelbaum FR, Willman CL (1997) Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 89:3323–3329PubMedGoogle Scholar
  4. 4.
    Bauduer F, Ducout L, Dastugue N, Capdupuy C, Renoux M (1999) De novo and secondary acute myeloid leukemia in patients over the age of 65: a review of fifty-six successive and unselected cases from a general hospital. Leuk Lymphoma 35:289–296PubMedCrossRefGoogle Scholar
  5. 5.
    Hassan HT, Rees JK (1990) Relation between age and blast cell differentiation in acute myeloid leukaemia patients. Oncology 47:439–442PubMedCrossRefGoogle Scholar
  6. 6.
    Gahn B, Haase D, Unterhalt M, Drescher M, Schoch C, Fonatsch C, Terstappen LW, Hiddemann W, Buchner T, Bennett JM, Wormann B (1996) De novo AML with dysplastic hematopoiesis: cytogenetic and prognostic significance. Leukemia 10:946–951PubMedGoogle Scholar
  7. 7.
    Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100:4325–4336PubMedCrossRefGoogle Scholar
  8. 8.
    Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A (1998) 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 92:2322–2333PubMedGoogle Scholar
  9. 9.
    Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ, Wheatley K, Burnett AK, Goldstone AH (2001) The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98:1312–1320PubMedCrossRefGoogle Scholar
  10. 10.
    Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman P, Lee EJ, Moore JO, Powell BL, Schiffer CA (1995) Granulocyte–macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. N Engl J Med 332:1671–1677PubMedCrossRefGoogle Scholar
  11. 11.
    Hiddemann W, Kern W, Schoch C, Fonatsch C, Heinecke A, Wormann B, Buchner T (1999) Management of acute myeloid leukemia in elderly patients. J Clin Oncol 17:3569–3576PubMedGoogle Scholar
  12. 12.
    Lowenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, Cauchie C, Peetermans M, Solbu G, Suciu S (1989) 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 European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol 7:1268–1274PubMedGoogle Scholar
  13. 13.
    Kahn SB, Begg CB, Mazza JJ, Bennett JM, Bonner H, Glick JH (1984) Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 2:865–870PubMedGoogle Scholar
  14. 14.
    Tilly H, Castaigne S, Bordessoule D, Casassus P, Le Prise PY, Tertian G, Desablens B, Henry-Amar M, Degos L (1990) Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 8:272–279PubMedGoogle Scholar
  15. 15.
    Ruutu T, Almqvist A, Hallman H, Honkanen T, Jarvenpaa E, Jarventie G, Koistinen P, Koivunen E, Lahtinen R, Lehtinen M (1994) Oral induction and consolidation of acute myeloid leukemia with etoposide, 6-thioguanine, and idarubicin (ETI) in elderly patients: a randomized comparison with 5-day TAD. Finnish Leukemia Group. Leukemia 8:11–15PubMedGoogle Scholar
  16. 16.
    Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH (2004) A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood 103:479–485PubMedCrossRefGoogle Scholar
  17. 17.
    Legha SS, Benjamin RS, Mackay B, Ewer M, Wallace S, Valdivieso M, Rasmussen SL, Blumenschein GR, Freireich EJ (1982) Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 96:133–139PubMedGoogle Scholar
  18. 18.
    Casper ES, Gaynor JJ, Hajdu SI, Magill GB, Tan C, Friedrich C, Brennan MF (1991) A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 68:1221–1229PubMedCrossRefGoogle Scholar
  19. 19.
    Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96:4075–4083PubMedGoogle Scholar
  20. 20.
    Tafuri A, Gregorj C, Petrucci MT, Ricciardi MR, Mancini M, Cimino G, Mecucci C, Tedeschi A, Fioritoni G, Ferrara F, Di Raimondo F, Gallo E, Liso V, Fabbiano F, Cascavilla N, Pizzolo G, Camera A, Pane F, Lanza F, Cilloni D, Annino L, Vitale A, Vegna ML, Vignetti M, Foa R, Mandelli F (2002) MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. Blood 100:974–981PubMedCrossRefGoogle Scholar
  21. 21.
    Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD (2003) Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 21:4642–4649PubMedCrossRefGoogle Scholar
  22. 22.
    Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman PP, Lee EJ, Moore JO, Powell BL, Baer MR, Bloomfield CD, Schiffer CA (2001) 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 98:548–553PubMedCrossRefGoogle Scholar
  23. 23.
    Rowe JM, Andersen JW, Mazza JJ, Bennett JM, Paietta E, Hayes FA, Oette D, Cassileth PA, Stadtmauer EA, Wiernik PH (1995) A randomized placebo-controlled phase III study of granulocyte–macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood 86:457–462PubMedGoogle Scholar
  24. 24.
    Lowenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef GE, Vellenga E, Wijermans P, Berneman Z, Dekker AW, Stryckmans P, Schouten H, Jehn U, Muus P, Sonneveld P, Dardenne M, Zittoun R (1997) Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group. Blood 90:2952–2961PubMedGoogle Scholar
  25. 25.
    Godwin JE, Kopecky KJ, Head DR, Willman CL, Leith CP, Hynes HE, Balcerzak SP, Appelbaum FR (1998) A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood 91:3607–3615PubMedGoogle Scholar
  26. 26.
    Dillman RO, Davis RB, Green MR, Weiss RB, Gottlieb AJ, Caplan S, Kopel S, Preisler H, McIntyre OR, Schiffer C (1991) A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood 78:2520–2526PubMedGoogle Scholar
  27. 27.
    Archimbaud E, Jehn U, Thomas X, De Cataldo F, Fillet G, Belhabri A, Peaud PY, Martin C, Amadori S, Willemze R (1999) Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. Leukemia 13:843–849PubMedCrossRefGoogle Scholar
  28. 28.
    A systematic collaborative overview of randomized trials comparing idarubicin with daunorubicin (or other anthracyclines) as induction therapy for acute myeloid leukaemia. AML Collaborative Group (1998) Br J Haematol 103:100–109CrossRefGoogle Scholar
  29. 29.
    Lowenberg B, Suciu S, Archimbaud E, Haak H, Stryckmans P, de Cataldo R, Dekker AW, Berneman ZN, Thyss A, van der Lelie J, Sonneveld P, Visani G, Fillet G, Hayat M, Hagemeijer A, Solbu G, Zittoun R (1998) 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. European Organization for the Research and Treatment of Cancer and the Dutch–Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol 16:872–881PubMedGoogle Scholar
  30. 30.
    Burnett AK, Milligan DW, Prentice AG, Goldstone AH, McMullin MF, Hills RK (2005). Modification or dose or treatment duration has no impact on outcome of AML in older patients: preliminary results of the UK NCRI AML14 trial. Blood 106:162a (Abstract)Google Scholar
  31. 31.
    Bloomfield CD (1985) Post-remission therapy in acute myeloid leukemia. J Clin Oncol 3:1570–1572PubMedGoogle Scholar
  32. 32.
    Cassileth PA, Begg CB, Bennett JM, Bozdech M, Kahn SB, Weiler C, Glick JH (1984) A randomized study of the efficacy of consolidation therapy in adult acute nonlymphocytic leukemia. Blood 63:843–847PubMedGoogle Scholar
  33. 33.
    Cassileth PA, Lynch E, Hines JD, Oken MM, Mazza JJ, Bennett JM, McGlave PB, Edelstein M, Harrington DP, O’Connell MJ (1992) Varying intensity of postremission therapy in acute myeloid leukemia. Blood 79:1924–1930PubMedGoogle Scholar
  34. 34.
    Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 331:896–903PubMedCrossRefGoogle Scholar
  35. 35.
    Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE (2001) Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. 98:1302–1311Google Scholar
  36. 36.
    Sperr WR, Piribauer M, Wimazal F, Fonatsch C, Thalhammer-Scherrer R, Schwarzinger I, Geissler K, Knobl P, Jager U, Lechner K, Valent P (2004) A novel effective and safe consolidation for patients over 60 years with acute myeloid leukemia: intermediate dose cytarabine (2×1 g/m2 on days 1, 3, and 5). Clin Cancer Res 10:3965–3971PubMedCrossRefGoogle Scholar
  37. 37.
    Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrere F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T (2005) Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood 106:27–34PubMedCrossRefGoogle Scholar
  38. 38.
    Grigg AP, Reynolds J, McQuillan A, Juneja SK, Di Iulio J, Hui C, Smith C, Kimber R, Bradstock KF (2005) Prognostic features for response and survival in elderly patients with de novo acute myeloid leukemia treated with mitoxantrone and intermediate dose cytarabine. Leuk Lymphoma 46:367–375PubMedCrossRefGoogle Scholar
  39. 39.
    Ossenkoppele GJ, Graveland WJ, Sonneveld P, Daenen SM, Biesma DH, Verdonck LF, Schaafsma MR, Westveer PH, Peters GJ, Noordhuis P, Muus P, Selleslag D, van der Holt B, Delforge M, Lowenberg B, Verhoef GE (2004) The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients. Blood 103:2908–2913PubMedCrossRefGoogle Scholar
  40. 40.
    Bertz H, Potthoff K, Finke J (2003) Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol 21:1480–1484PubMedCrossRefGoogle Scholar
  41. 41.
    Baer MR, George SL, Dodge RK, O’Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA (2002) Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood 100:1224–1232PubMedGoogle Scholar
  42. 42.
    Larson RA, Boogaerts M, Estey E, Karanes C, Stadtmauer EA, Sievers EL, Mineur P, Bennett JM, Berger MS, Eten CB, Munteanu M, Loken MR, Van Dongen JJ, Bernstein ID, Appelbaum FR (2002) Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia 16:1627–1636PubMedCrossRefGoogle Scholar
  43. 43.
    Schoch C, Kern W, Schnittger S, Buchner T, Hiddemann W, Haferlach T (2004) The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica 89:1082–1090PubMedGoogle Scholar
  44. 44.
    Casasnovas RO, Slimane FK, Garand R, Faure GC, Campos L, Deneys V, Bernier M, Falkenrodt A, Lecalvez G, Maynadie M, Bene MC (2003) Immunological classification of acute myeloblastic leukemias: relevance to patient outcome. Leukemia 17:515–527PubMedCrossRefGoogle Scholar
  45. 45.
    Chang H, Salma F, Yi QL, Patterson B, Brien B, Minden MD (2004) Prognostic relevance of immunophenotyping in 379 patients with acute myeloid leukemia. Leuk Res 28:43–48PubMedCrossRefGoogle Scholar
  46. 46.
    Ogata K, Yokose N, Shioi Y, Ishida Y, Tomiyama J, Hamaguchi H, Yagasaki F, Bessyo M, Sakamaki H, Dan K, Kuriya S (2001) Reappraisal of the clinical significance of CD7 expression in association with cytogenetics in de novo acute myeloid leukaemia. Br J Haematol 115:612–615PubMedCrossRefGoogle Scholar
  47. 47.
    Tien HF, Wang CH (1998) CD7 positive hematopoietic progenitors and acute myeloid leukemia and other minimally differentiated leukemia. Leuk Lymphoma 31:93–98PubMedGoogle Scholar
  48. 48.
    Saxena A, Sheridan DP, Card RT, McPeek AM, Mewdell CC, Skinnider LF (1998) Biologic and clinical significance of CD7 expression in acute myeloid leukemia. Am J Hematol 58:278–284PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Je-Hwan Lee
    • 1
  • Seong-Jun Choi
    • 1
  • Jung-Hee Lee
    • 1
  • Jae-Hoo Park
    • 2
  • Hawk Kim
    • 2
  • Young-Don Joo
    • 3
  • Won Sik Lee
    • 3
  • Dae Young Zang
    • 4
  • Hyo Jung Kim
    • 4
  • Kyoo-Hyung Lee
    • 1
  • Cooperative Study Group A for Hematology
  1. 1.Department of Internal MedicineAsan Medical CenterSeoulSouth Korea
  2. 2.Division of Hematology–Oncology, Ulsan University HospitalUniversity of Ulsan College of MedicineUlsanSouth Korea
  3. 3.Department of Internal Medicine, Busan Paik HospitalInje University College of MedicineBusanSouth Korea
  4. 4.Department of Internal Medicine, Hallym University Medical CenterHallym University College of MedicineAnyangSouth Korea

Personalised recommendations