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:

Myelodysplesias

Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group

Leukemia volume 19, pages 1929–1933 (2005)Cite this article

Abstract

In this randomized phase III study of the EORTC Leukemia Cooperative Group, patients with myelodysplastic syndromes (MDS) with 10–30% bone marrow blasts and hematopoietic failure were treated with low-dose cytosine arabinoside (LD-AraC) (2 × 10 mg/m2/day subcutaneously (s.c.) days 1–14) either alone or in combination with rhGM-CSF or interleukin-3 (IL-3) both given s.c. at a dose of 150 μg/day from day 8 to 21. A total of 180 evaluable patients with a median age of 65 years and refractory anemia with an excess of blasts (RAEB, n=107) or RAEB in transformation (RAEBt, n=73) were randomized. There were no differences among the three treatment regimens with respect to numbers of courses applied or treatment delays. Hemorrhage occurred in approximately 40% in all arms, whereas infection rates were higher in the granulocyte/macrophage colony stimulating factor (GM-CSF)- or IL3-containing arm. The overall response rate was 38.6% with no statistically significant difference among the three arms. In summary, a substantial proportion of patients had achieved relatively durable responses in all the three arms. No influence of either growth factor was detected on the grade of cytopenia. Thus, the combination of LD-AraC with GM-CSF or IL-3 cannot be recommended for routine use in a high-risk MDS population.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Greenberg P, Cox C, LeBeau M, Fenaux P, Morel P, Sanz G et al. International Scoring System for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    CAS  PubMed  Google Scholar 

  2. Fenaux P, Morel P, Rose C, Lai JL, Jouet JP, Bauters F . Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy. Br J Haematol 1991; 77: 497–501.

    Article  CAS  PubMed  Google Scholar 

  3. De Witte T, Suciu G, Peetermans M, Fenaux P, Strijckmans P, Hayat M et al. Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myelogenous leukemia following MDS of more than 6 months duration. Leukemia 1995; 9: 1805–1811.

    CAS  PubMed  Google Scholar 

  4. deWitte T, Suciu S, Verhoef G, Labar B, Archimbaud E, Aul C et al. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS (AML-MDS). Blood 2001; 98: 2326–2331.

    Article  CAS  Google Scholar 

  5. Visani G, Malagola M, Piccaluga PP, Isidori A . Low dose Ara-C for myelodysplastic syndromes: is it still a current therapy? Leuk Lymphoma 2004; 45: 1531–1538.

    Article  PubMed  Google Scholar 

  6. Aul C, Schneider W . The role of low-dose cytosine arabinoside and aggressive chemotherapy in advanced myelodysplastic syndromes. Cancer 1989; 64: 1812–1818.

    Article  CAS  PubMed  Google Scholar 

  7. Miller KB, Kyungmann K, Morrison FS, Winter JN, Bennett JM, Neiman RS et al. The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. Ann Hematol 1992; 65: 162–168.

    Article  CAS  PubMed  Google Scholar 

  8. Mittermüller J, Kolb HJ, Gerhartz HH, Wilmanns W . In vivo differentiation of leukaemic blasts and effect of low dose AraC in a marrow grafted patient with leukaemic relapse. Br J Haematol 1986; 62: 757–762.

    Article  PubMed  Google Scholar 

  9. Layton DM, Mufti GJ, Lyons J, Janssen JWG, Bartram CR . Loss of ras oncogene mutation in a myelodysplastic syndrome after low-dose cytarabine therapy. N Engl J Med 1988; 318: 1468–1471.

    Article  CAS  PubMed  Google Scholar 

  10. Rossi H, O'Donnell J, Sarcinelli F, Stewart FM, Quesenberry PJ, Becker PS . Granulocyte–macrophage colony-stimulating factor (GM-CSF) priming with successive concomitant low-dose Ara-C for elderly patients with secondary/refractory acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia 2002; 16: 310–315.

    Article  CAS  PubMed  Google Scholar 

  11. Gerhartz HH, Marcus R, Delmer A, Zwierzina H, Suciu S, Dardenne M et al. A randomized phase II study of low-dose cytosine arabinoside (LD-araC) plus granulocyte/macrophage colony-stimulating factor (rhGM-CSF) in myelodysplastic syndromes (MDS) with a high risk of developing leukemia. Leukemia 1994; 8: 16–23.

    CAS  PubMed  Google Scholar 

  12. Geissler RG, Schulte P, Ganser A . Clinical use of hematopoietic growth factors in patients with myelodysplastic syndromes. Int J Hematol 1997; 65: 339–354.

    Article  CAS  PubMed  Google Scholar 

  13. Ganser A, Seipelt G, Lindemann A, Ottmann OG, Falk S, Eder M et al. Effects of recombinant human interleukin-3 on patients with myelodysplastic syndromes. Blood 1990; 76: 455–462.

    CAS  PubMed  Google Scholar 

  14. Gerhartz H, Zwierzina H, Walther J, Fenaux P, Hayat M, Jacobs A et al. Interleukin-3 plus low dose cytosine arabinoside for advanced myelodysplasia: a pilot study. Cancer Invest 1996; 14: 4–8.

    Article  Google Scholar 

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

    Chapter  Google Scholar 

  16. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Brackx B, Broeders L, Touw I, Lowenberg B . Blast colony-forming cells in myelodysplastic syndrome: decreased potential to generate erythroid precursors. Leukemia 1993; 7: 75–77.

    Google Scholar 

  18. Mufti GJ, Stevens J, Oscier D, Hamblin TG . Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1986; 59: 425–432.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by an educational grant from Sandoz/Novartis and by grant numbers 5U10-CA11488-20 through 5U10-CA11488-35 from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute (Bethesda, MD, USA). Additional members of the EORTC CLG who participated to this study: Drs P Stryckmans/D Bron (Institut J Bordet, Brussels), Drs A Louwagie/D Selleslag (AZ St Jan, Brugge), Drs M Peetermans/Z Berneman (UZ Antwerpen), Dr B Coiffier (Centre Hospitalier Lyon Sud), Dr A Thyss (Centre A Lacassagne, Nice), Dr J-H Bourhis (Institut G Roussy, Villejuif), Dr D Fière (Hopital Edouard Herriot, Lyon), Drs R Zittoun/JP Marie (Hotel-Dieu, Paris), Dr D Maraninchi (Institut Paoli-Calmettes, Marseille), Dr E Baumelou (Centre Foch, Suresnes), Drs B Lowenberg/P Sonnenveld (Erasmus Medical Center, Rotterdam), Dr H Gerhartz (Klinikum Grosshadern, Munich), Dr M Ribeiro (Hospital Escolar San Joao, Porto), Dr I Ben-Bassat (Chaim Sheba Medical Center, Tel-Hashomer), Dr B Labar (Hospital Rebro, Zagreb). Thanks to the former EORTC data manager: M Dardenne.

Author information

Authors and Affiliations

  1. University Hospital, Medical University Innsbruck, Innsbruck, Austria

    H Zwierzina & J Loeffler-Ragg

  2. EORTC Data Center, Brussels, Belgium

    S Suciu & G Solbu

  3. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    R Neuwirtova & J Cermak

  4. Avicenne Hospital, Paris XIII University, Paris, France

    P Fenaux

  5. Ibni Sina Hospital, Ankara, Turkey

    M Beksac

  6. Hotel Dieu, Nantes, France

    J Harousseau

  7. Klinikum Grosshadern, Munich, Germany

    V Nuessler

  8. University Medical Center, Leiden, The Netherlands

    R Willemze

  9. St Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    T de Witte

  10. University Tor Vergata, Rome, Italy

    S Amadori

Authors
  1. H Zwierzina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Suciu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Loeffler-Ragg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Neuwirtova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P Fenaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Beksac
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Harousseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. V Nuessler
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Cermak
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Solbu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R Willemze
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T de Witte
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S Amadori
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the EORTC Leukemia Cooperative Group

Corresponding author

Correspondence to H Zwierzina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zwierzina, H., Suciu, S., Loeffler-Ragg, J. et al. Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group. Leukemia 19, 1929–1933 (2005). https://doi.org/10.1038/sj.leu.2403934

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403934

Keywords

Search

Advanced search

Quick links