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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.

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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.

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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

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  1. H Zwierzina
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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

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