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Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia

Leukemia volume 15, pages 1331–1338 (2001)Cite this article

Abstract

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 μg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 × 109/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 × 109/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P = 0.015) and a trend to reduced number of days with fever >38.0°C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.

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Acknowledgements

This work was supported by research grant RG950971 from the National Health and Medical Research Council of Australia, by Pharmacia and Upjohn Australia, and by AMRAD Pharmaceuticals Pty Ltd, who provided lenograstim for this study. We gratefully acknowledge the contributions of the numerous data managers who provided information from contributing hospitals. We particularly acknowledge the assistance of the members of the independent safety monitoring committee (John Simes, Richard Fisher and Max Whiteside) who oversaw the conduct of this study. The following members of the Australian Leukaemia Study Group also contributed patients into this study: G Dart, J Ho, N Horvath, Royal Adelaide Hospital, Adelaide; P Elliott, Alfred Hospital, Melbourne; I Prosser, M Webb, Canberra Hospital, Canberra; F Cordingley, Fremantle Hospital, Perth; R Kimber, Royal Hobart Hospital, Hobart; J Gallo, P Motum, D Rosenfeld, Liverpool Hospital, Sydney; S Deveridge, M Seldon, A Spencer, Newcastle Mater Hospital, Newcastle; M Wolf, Peter MacCallum Cancer Institute, Melbourne; P Marlton, Princess Alexandra Hospital, Brisbane; P Bardy, J Szer, Royal Melbourne Hospital, Melbourne; D Ma, Royal North Shore Hospital, Sydney; R Baker, R Herrmann, Royal Perth Hospital, Perth; J Gibson, H Kronenberg, Royal Prince Alfred Hospital, Sydney; I Bunce, Wesley Medical Centre, Brisbane; P Castaldi, M Hertzberg, Westmead Hospital, Sydney. We are also grateful to Andrew Dalton, health economist, for invaluable advice on methods for resource analysis.

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Authors and Affiliations

  1. Westmead Hospital, Westmead, NSW, Australia

    K Bradstock & D Gottlieb

  2. Trial Centre, Peter MacCallum Cancer Institute, East Melbourne, Australia

    J Matthews & H Baxter

  3. Royal Prince Alfred Hospital, Camperdown, NSW, Australia

    G Young & D Joshua

  4. Royal Hobart Hospital, Hobart, Tasmania, Australia

    R Lowenthal

  5. Royal North Shore Hospital, St Leonards, NSW, Australia

    C Arthur

  6. St George Hospital, Kogarah, NSW, Australia

    T Brighton

  7. Royal Perth Hospital, Perth, Western Australia, Australia

    P Cannell

  8. Liverpool Hospital, Liverpool, NSW, Australia

    L Dunlop

  9. Royal Brisbane Hospital, Herston, Queensland, Australia

    S Durrant

  10. Newcastle Mater Hospital, Waratah, NSW, Australia

    A Enno & A Gillett

  11. Wesley Medical Centre, Brisbane, Queensland, Australia

    J Bashford & P Eliadis

  12. Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

    D Gill

  13. Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia

    H Januszewicz

  14. Fremantle Hospital, Fremantle, Western Australia, Australia

    M Leahy

  15. Alfred Hospital, Prahran, Victoria, Australia

    A Schwarer

  16. Mater Miseracordiae Hospital, South Brisbane, Queensland, Australia

    K Taylor

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Bradstock, K., Matthews, J., Young, G. et al. Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia. Leukemia 15, 1331–1338 (2001). https://doi.org/10.1038/sj.leu.2402218

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