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Acute Leukemia Forum 2000, Advances and Controversies in the Therapy of Acute Myelogenous Leukemia

Uncertainties in the standard care of acute myelogenous leukemia

Leukemia volume 15, pages 677–679 (2001)Cite this article

It is perhaps extraordinary how many treatment modalities for patients with AML are considered standard care without data that support such a premise. In some instances there are at least major question marks around a particular concept or therapy that is administered. Such observations apply to induction therapy, post remission-therapy, therapy of secondary leukemias and bone marrow transplantation.

The gold standard for induction therapy in AML, in most parts of the world, is the combination with which most new or different induction regimens are compared; that is, a standard 3+7 regimen, which consists of daunorubicin 45 mg/m2 for 3 days together with cytarabine 100 mg/m2 by continuous infusion for 7 days. The choice of anthracycline has actually been studied extensively in well-conducted prospective randomized studies. Yet, strangely enough, very few data support the choice of daunorubicin at this dose in preference to other agents. In fact, the opposite is true. In patients younger than 55–60 years, multiple prospective randomized studies have compared daunorubicin 45 mg/m2 with idarubicin, amsacrine, mitroxantrone or aclacinomycin A, while keeping the dose of cytarabine constant. Virtually all of these agents proved superior to daunorubicin 45–50 mg/m2. In this age group, four randomized clinical trials, that included over 800 patients, compared idarubicin at a dose of 12–13 mg/m2 with daunorubicin 45 mg/m2 while maintaining the same dose of cytarabine.1234 Each of these studies demonstrated a superior response rate for idarubicin in younger adults. Furthermore, a meta-analysis of these studies conducted by the AML Collaborative Group in Great Britain5 confirmed that the complete response rate associated with idarubicin after only one cycle of therapy was significantly higher than that associated with daunorubicin. Similar trials using amsacrine,6 mitoxantrone7 or aclacinomycin A8 all showed either a statistically significant improvement, or at least a very strong trend, in favor of an alternate anthracycline or anthraquinone when compared with daunorubicin 45–50 mg/m2. Thus, virtually any anthracycline or anthraquinone that has been compared with daunorubicin at a dose of 45 mg/m2 in adult patients with AML who are less than 55–60 years has been found to be superior. It remains unclear why daunorubicin at this dose remains the standard of care in many parts of the world.

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References

  1. Berman E, Heller G, Santorsa J, McKenzie S, Gee T, Kempin S, Gulati, S . Andreeff M, Kolitz J, Gabrilove J. 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

    CAS  PubMed  Google Scholar 

  2. Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL . A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group J Clin Oncol 1992 10: 1103–1111

    Article  CAS  Google Scholar 

  3. Wiernik PH, Banks PL, Case DC, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB . Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia Blood 1992 79: 313–319

    CAS  PubMed  Google Scholar 

  4. Mandeli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R . A randomized clinical trial comparing idarubicin and cytarabine todaunorubicin and cytarabine of treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA Eur J Cancer 1991 27: 750–755

    Article  Google Scholar 

  5. AML Collaborative Group . A systematic collaborative overview of randomized trials comparing idrubicin with daunorubicin (or other anthracyclines) as induction therapy for acute myeloid leukaemia Br J Haematol 1998 103: 100–109

    Article  Google Scholar 

  6. Berman E, Arlin ZA, Gaynar J, Miller W, Gee T, Kempin SJ, Mertelsmann R, Andreeff M, Reich L, Nahmias N . Comparative trial of cytarabine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol Leukemia 1989 3: 115–121

    CAS  PubMed  Google Scholar 

  7. Arlin Z, Case DC, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K . Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooparative Group Leukemia 1990 4: 177–183

    CAS  PubMed  Google Scholar 

  8. Hansen OP, Pedersen-Bjergaard J, Brincker H, Boesen AM, Christensen BE, Drivsholm A, Hippe E, Jans H, Jensen KB . 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 ofHematology Study Group Leukemia on AML, Denmark Leukemia 1991 5: 510–516

    CAS  PubMed  Google Scholar 

  9. Hewlett J, Kopecky KJ, Head D, Eyre HJ, Elias L, Kingsbury L, Balcerzak SP, Dabich L, Haynes H, Bickers JN . A prospective evaluation of the roles 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

    CAS  PubMed  Google Scholar 

  10. Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Haynes HE, Welborn JL, Simon SR, Grever M . A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwestern Oncology Group study Blood 1996 88: 2841–2851

    CAS  PubMed  Google Scholar 

  11. Rowe JM, Andersen JW, Mazza JJ, Bennett JM, Paietta E, Hayes FA, Oette D, Cassileth PA, Stadmauer EA, Wiernik PH . Randomized placebo-controlled phase III study of granulocyte–macrophage colony-stimulating factor in adult patients (>55–70 years) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490) Blood 1995 86: 457–462

    CAS  PubMed  Google Scholar 

  12. Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary A . A phase III study of daunorubicin vs idarubicin vs mitoxantrone for older adult patients (>55 years) with acute myelogenous leukemia (AML): a study of the Eastern Cooperative Oncology Group (E2993) Blood 1998 92: (Suppl. 1) 1284a

    Google Scholar 

  13. Byrd JC, Dodge RK, Carroll A, Baer MR, Edwards C, Stamberg J, Qumsiyeh M, Moore JO, Mayer RJ, Davey F, Schiffer CA, Bloomfield CD . Patients with t(8;21)(q21;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

    Article  CAS  Google Scholar 

  14. Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, Wheatley K . Randomized comparision of autologous bone marrow transplantation to intensive chemotherapy for acute myeloid leukemia in first remission: results of MRC AML10 trial. UK Medical Research Council adult and children's leukemia patients Lancet 1998 351: 700–708

    Article  CAS  Google Scholar 

  15. Quesnel B, Kantarjian HM, Pjergaard JP . Therapy-related acute myeloid leukemia t(8;21), inv(16) and t(8;16): a report on 25 cases and review of the literature J Clin Oncol 1993 11: 2370–2379

    Article  CAS  Google Scholar 

  16. Kantarjian HM, Estey EH, Keating MJ . Treatment of therapy-related leukemia and myeloid dysplastic syndrome Hematol/Oncol Clin N Am 1993 7: 81–87

    Article  CAS  Google Scholar 

  17. Preisler H, Early A, Raza A . Therapy of secondary acute nonlymphocytic leukemia with cytarabine New Engl J Med 1983 308: 21–24

    Article  CAS  Google Scholar 

  18. Clavio M, Carrara P, Miglino M . High efficacy of cytarabine-containing therapy (FLAG-FLANG) in pure risk acute myeloid leukemia Haematologica 1996 81: 513–520

    CAS  PubMed  Google Scholar 

  19. Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G . 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 Hematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups New Engl J Med 1995 332: 217–223

    Article  CAS  Google Scholar 

  20. Cassileth PA, Harrington D, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd D, Bennett JM, Blume KG, Head DR, Wiernik PH . A comparison of chemotherapy versus autologous bone marrow transplantation versus genetic bone marrow transplantation in first remission of adult acute myeloid leukemia: an intergroup study (E3489) New Engl J Med 1998 339: 1649–1656

    Article  CAS  Google Scholar 

  21. Harousseau JL, Cahn JY, Pignon B, Witz F, Milpied N, Delain M, Lioure B, Lamy T, Desablens B, Guilhot F, Caillot D, Abgrall JF, Francois S, Briere J, Guyotat D, Casassus P, Audhuy B, Tellier Z, Hurteloup P, Herve P . Comparison of autologous bone marrow transplantation and intensive chemotherapy as post-remission therapy in adult acute myeloid leukemia. The Group Ouest Est Leucemies Aigues Myeloblastiques (GOELAM) Blood 1997 90: 2978–2986

    CAS  PubMed  Google Scholar 

  22. Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenati MJ, Tantravahi R, Patil SR, Davey FR, Berg DT, Schiffer CA, Arthur DC, Mayer RJ . Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetics subtype Cancer Res 1998 58: 4173–4179

    CAS  Google Scholar 

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  1. Department of Hematology and Bone Marrow Transplantation, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

    JM Rowe

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Rowe, J. Uncertainties in the standard care of acute myelogenous leukemia. Leukemia 15, 677–679 (2001). https://doi.org/10.1038/sj.leu.2402066

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