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Therapy

Effect of priming with granulocyte–macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group

Leukemia volume 21, pages 453–461 (2007)Cite this article

Abstract

In a multicenter trial, 259 young adults (15–49 years) with newly diagnosed acute myeloid leukemia (AML) were first randomized to receive a timed-sequential induction regimen given either alone (135 patients) or concomitantly with granulocyte–macrophage colony-stimulating factor (GM-CSF) (124 patients). Patients reaching complete remission (CR) were then randomized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses. In the appropriate arm, GM-CSF was given concurrently with chemotherapy during all cycles of consolidation. CR rates were significantly better in the GM-CSF arm (88 vs 78%, P<0.04), but did not differ after salvage. Patients receiving GM-CSF had a higher 3-year event-free survival (EFS) estimate (42 vs 34%), but GM-CSF did not impact on overall survival. Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy (P=0.05) in terms of EFS than patients with other cytogenetics. This was also confirmed when considering only patients following the second randomization, or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR. Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML.

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Acknowledgements

This work was supported in part by Schering Plough (Kenilworth, NJ, USA) and Amgen (Neuilly sur Seine, France) which provided grants to the Edouard Herriot Hospital (Department of Hematology) for central data management. Schering Plough provided molgramostim (GM-CSF) free of charge.

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Authors and Affiliations

  1. Department of Hematology, Hôpital Edouard Herriot, Lyon, France

    X Thomas, Q-H Le, M Elhamri & M Michallet

  2. Department of Hematology, Hôpital Saint-Louis, Paris, France

    E Raffoux & H Dombret

  3. Department of Hematology, Hôpital Claude Huriez, Lille, France

    S de Botton, B Quesnel & C Preudhomme

  4. Department of Hematology, Hôpital Henri Mondor, Créteil, France

    C Pautas & C Cordonnier

  5. Department of Hematology, Institut Gustave Roussy, Villejuif, France

    P Arnaud & J-H Bourhis

  6. Department of Hematology, Hôpital des Armées Percy, Clamart, France

    T de Revel

  7. Department of Hematology, Hôpital Georges Clémenceau, Caen, France

    O Reman

  8. Department of Hematology, Hôpital André Mignot, Versailles, France

    C Terré & S Castaigne

  9. Department of Hematology, Centre Hospitalier, Annecy, France

    B Corront

  10. Department of Hematology, Hôpital Avicenne, Bobigny, France

    C Gardin & P Fenaux

  11. Department of Hematology, Laboratoire de Biostatistiques, Pierre-Bênite, France

    Q-H Le

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  1. X Thomas
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  15. M Elhamri
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  16. P Fenaux
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  18. M Michallet
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  20. H Dombret
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Corresponding author

Correspondence to X Thomas.

Appendix

Appendix

The following centers and persons participated in the ALFA-9802 study: Study coordinator – X Thomas (Hôpital E Herriot, Lyon, France); ALFA group chairman – S Castaigne (Hôpital A Mignot, Versailles, France); ALFA group secretary – H Dombret (Hôpital Saint-Louis, Paris, France); Statistician ALFA-9802 study – QH Le (Laboratoire de Biostatistiques, Centre Hospitalier Lyon-Sud, Pierre-Bênite, France); Cytogenetic review – C Terré (Hôpital A Mignot, Versailles, France) and C Bastard (Centre H Becquerel, Rouen, France); Cytology review – M Amar (Hôpital Beaujon, Paris, France); Central data management – M Elhamri (Unité de Recherche Clinique, Département d'Hématologie, Hôpital E Herriot, Lyon, France); Pharmacist coordinator – C Pivot (Antenne Pharmaceutique, Hôpital E Herriot, Lyon, France); Participating centers (and investigators) – Hôpital E Herriot, Lyon, France (X Thomas, E Archimbaud (Eric Archimbaud died on March 25, 1998), M Michallet, D Fiere, C Charrin, I Tigaud, S Hayette, D Treille-Ritouet, C Dumontet, QH Le, E Tavernier, A Thiebaut, J Troncy, F Nicolini, E Wattel, M Elhamri); Hôpital Saint-Louis, Paris, France (H Dombret, JM Micléa, E Raffoux, N Boissel, L Degos, JM Cayuela, S Chevret, A de Labarthe, H Espérou, E Gluckman, T Leblanc, V Levy, O Maarek, D Réa, G Socié, J Soulier, C Chomienne, MT Daniel, J Delaunay, F Treilhou); Hôpital C Huriez, Lille, France (S de Botton, B Quesnel, C Preudhomme, F Bauters, JP Jouet, JL Lai, P Lepelley, H Djeda); Hôpital H Mondor, Créteil, France (C Cordonnier, S Maury, D Bories, H Jouault, M Kuentz, C Pautas, K Yacouben, J Beaune); Institut Gustave Roussy, Villejuif, France (JH Bourrhis, P Arnaud, C Fermé, N Itzhar, A Bernheim, N Fresnoy, M Leste); Centre Hospitalier, Annecy, France (C Martin, B Corront); Hôpital G Clémenceau, Caen, France (O Reman, E Lepesant); Hôpital A Mignot, Versailles, France (S Castaigne, P Rousselot, C Terré, AL Taksin, JN Bastie, F Suzan, P Piesvaux); Hôpital des Armées Percy, Clamart, France (T de Revel, T Fagot, G Nedellec, G Auzanneau, B Souleau, F Desangles); Hôpital Avicenne, Bobigny, France (P Fenaux, C Gardin, L Ades, J Briere, JJ Kiladjian, B Beve); Centre Jean Perrin, Clermont-Ferrand, France (JO Bay, B Choufi, M Legros, O Tournilhac); Hôpital V Provo, Roubaix, France (I Plantier, L Detourmignies); Hôpital Saint-Vincent, Lille, France (N Cambier); Centre Hospitalier, Meaux, France (C Soussain); Centre Hospitalier, Boulogne sur Mer, France (M Beaumont, P Agape, B Pollet); Centre René Huguenin, Saint-Cloud, France (M Janvier).

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Thomas, X., Raffoux, E., Botton, S. et al. Effect of priming with granulocyte–macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group. Leukemia 21, 453–461 (2007). https://doi.org/10.1038/sj.leu.2404521

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