Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report

Abstract

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Behar C, Suciu S, Benoit Y, Robert A, Vilmer E, Boutard P et al. Mitoxantrone containing regimen for treatment of childhood acute leukemia (AML) and analysis of prognostic factors: results of the EORTC Children Leukemia Cooperative Study 58872. Med Pediatr Oncol 1996; 26: 173–179.

    Article  CAS  Google Scholar 

  2. Creutzig U, Ritter J, Riehm H, Langermann H-J, Henze G, Kabisch H et al. Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78. Blood 1985; 65: 298–304.

    CAS  PubMed  Google Scholar 

  3. Creutzig U, Ritter J, Budde M, Jurgens H, Riehm H, Schellong G . Treatment results in childhood AML, with special reference to the German studies BFM-78 and BFM-83. Haematol Blood Transfus 1987; 31: 30–34.

    CAS  PubMed  Google Scholar 

  4. Woods WG, Kobrinsky N, Buckley J, Neudorf S, Sanders J, Miller L et al. Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: a Children's Cancer Group pilot study. J Clin Oncol 1993; 11: 1448–1457.

    Article  CAS  Google Scholar 

  5. Woods WG, Kobrinsky N, Buckley JD, Lee JW, Sanders J, Neudorf S et al. Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: a report from Children's Cancer Group. Blood 1996; 87: 4979–4989.

    CAS  PubMed  Google Scholar 

  6. Creutzig U, Ritter J, Schellong G . Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in the study AML-BFM-83 as compared with study AML-BFM-78. Blood 1990; 75: 1932–1940.

    CAS  PubMed  Google Scholar 

  7. Reid JM, Pendergrass TW, Krailo MD, Hammond GD, Ames MM . Plasma pharmacokinetics and cerebrospinal fluid concentration of idarubicin and idaribicinol in pediatric leukemia patients: a Children's Cancer Study Group Report. Cancer Res 1990; 50: 6525–6528.

    CAS  PubMed  Google Scholar 

  8. Wiernik PH, Banks PL, Case Jr DC, Arlin ZA, Periman PO, Todd MB 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.

    CAS  PubMed  Google Scholar 

  9. De Witte T, Suciu S, Selleslag D, Labar B, Roozendaal K, Zittoun R et al. Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: a phase II study (n° 06901) of the EORTC Leukemia Cooperative Group. Ann Haematol 1996; 72: 119–124.

    Article  CAS  Google Scholar 

  10. Mehta J, Powles R, Singhal S, Horton C, Hamblin M, Zomas A et al. Idarubicin, high-dose cytarabine, and etoposide for induction of remission in acute leukemia. Semin Hematol 1996; 33: 18–23.

    CAS  PubMed  Google Scholar 

  11. Wolf SN, Herzig RH, Fay JW, Phillips GL, Lazarus HM, Flexner JM et al. High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results. J Clin Oncol 1989; 7: 1260–1267.

    Article  Google Scholar 

  12. Ravindranath Y, Steuber CP, Krischer J, Civin CI, Ducore J, Vega R et al. High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group Study. J Clin Oncol 1991; 9: 572–580.

    Article  CAS  Google Scholar 

  13. Gray R, Wheatley K . How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplant 1991; 7: 9–12.

    PubMed  Google Scholar 

  14. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR et al. Proposed revised criteria for the classification of the acute myeloid leukemia: a report of the French–American–British Cooperative Group. Ann Intern Med 1985; 103: 620–625.

    Article  CAS  Google Scholar 

  15. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposal for the recognition of minimally differentiated acute myeloid leukaemias (AML-M0). Br J Haematol 1991; 78: 325–329.

    Article  CAS  Google Scholar 

  16. Mitelman F (ed). ISCN 1995: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S Karger, 1995.

    Google Scholar 

  17. Keating S, Suciu S, de Witte T, Zittoun R, Mandelli F, Belhabri A et al. The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial. Leukemia 2003; 17: 60–67.

    Article  CAS  Google Scholar 

  18. Keating MJ, Smith TL, Kantarjian H, Cork A, Walters R, Trujillo JM et al. Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome. Leukemia 1988; 2: 403–412.

    CAS  PubMed  Google Scholar 

  19. Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD et al. Report of the National Cancer Institute-sponsored workshop on definitions and response in acute myeloid leukemia. J Clin Oncol 1990; 8: 813–819.

    Article  CAS  Google Scholar 

  20. Kalbfleisch JD, Prentice RL . The Survival Analysis of Failure Time Data., 2nd edn, Wiley Series in Probabilities and Statistics. New Jersey: Wiley Inter-Science, 2002.

    Book  Google Scholar 

  21. Kaspers G, Creutzig V . Pediatric acute myeloid leukaemia: international progress and future directions. Leukemia 2005.

  22. Creutzig U, Ritter J, Zimmermann M, Reinhardt D, Hermann J, Berthold F et al. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin–Frankfurt–Munster 93. J Clin Oncol 2001; 19: 2705–2713.

    Article  CAS  Google Scholar 

  23. Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG 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.

    Article  CAS  Google Scholar 

  24. Chang M, Raimondi SC, Ravindranath Y, Carroll AJ, Camitta B, Gresik MV et al. Prognostic factors in children and adolescents with acute myeloid leukemia (excluding children with Down syndrome and acute promyelocytic leukemia): univariate and recursive partitioning analysis of patients treated on Pediatric Oncology Group (POG) Study 8821. Leukemia 2000; 14: 1201–1207.

    Article  CAS  Google Scholar 

  25. Wells RJ, Arthur DC, Srivastava A, Heerema NA, Le Beau M, Alonzo TA et al. Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213. Leukemia 2002; 16: 601–607.

    Article  CAS  Google Scholar 

  26. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al. 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 2002; 100: 4325–4336.

    Article  CAS  Google Scholar 

  27. Rubnitz JE, Raimondi SC, Tong X, Srivastava DK, Razzouk BI, Shurtleff SA et al. Favorable impact of the t(9;11) in childhood acute myeloid leukaemia. J Clin Oncol 2002; 20: 2302–2309.

    Article  CAS  Google Scholar 

  28. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G et al. 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 1998; 92: 2322–2333.

    CAS  PubMed  Google Scholar 

  29. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A 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.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from Télévie 2001 (grant no. 7.4561.01) and the National Cancer Institute (grant nos. 5U10-CA11488-18 through 5U10-CA11488-35). The contents of this paper are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute (Bethesda, MD, USA). We acknowledge all additional members of the EORTC CLG who participated in these studies: Dr A Robert (Hôpital des Enfants, Toulouse), Dr P Philippet (Clinique de l’Espérance, Montegnée), Dr P Maes (AZ Middelheim, Antwerp), Dr D Plantaz (CHR, Grenoble); the members of the cytologic/immunologic subcommittee: Dr A Falkenrodt (Strasbourg), O Fenneteau (Paris), M Lagrange (Nice), AM Malet (Caen), AM Manel and E Homolle (Lyon); Dr N Dastugue (Toulouse), for the central review of cytogenetics. We thank EORTC data managers Christine Waterkeyn, Isabel VandeVelde and Gabriel Solbu. We acknowledge Saint Jude Children's Research Hospital for providing a SAS macro, allowing the computation of the cumulative incidences of relapse and death in CR.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to C Behar.

Additional information

Supplementary Information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Entz-Werle, N., Suciu, S., van der Werff ten Bosch, J. et al. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia 19, 2072–2081 (2005). https://doi.org/10.1038/sj.leu.2403932

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403932

Keywords

This article is cited by

Search

Quick links