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Autografting

Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis

Bone Marrow Transplantation volume 49, pages 485–491 (2014)Cite this article

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Abstract

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

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Acknowledgements

We thank Dr Andrea Gallamini and Dr Daniele Mattei (Azienda Ospedaliera S. Croce, Cuneo, Italy); Dr Fabio Ciceri and Dr Roberto Crocchiolo (Hematology and BMT Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy); Dr Valerio Zoli and Dr Ignazio Maiolino (Hematology and BMT Unit, Institute of Hematotherapy, Ospedale S. Camillo, Rome, Italy); Professor Paolo Corradini (Division of Hematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy and Department of Hematology, University of Milan, Milan, Italy) for providing and caring for study patients. We thank also Paolo Longoni and Marco Milanesi for technical assistance. The trial has been registered on ‘https://eudract.ema.europa.eu/’ with the number 2005-005384-28. Supported by an unrestricted grant from Roche Italy which had no role in the design of the study, the collection, analysis and interpretation of the data, nor on the decision to submit the manuscript or the writing of the manuscript itself.

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Authors and Affiliations

  1. Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy

    M Magni, M Di Nicola, P Matteucci, L Devizzi, A Guidetti, S Viviani & A M Gianni

  2. Department of Hematology I, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy

    C Patti, R Scimè & A Mulè

  3. Unit of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy

    A Rambaldi, T Intermesoli & P Viero

  4. S.C.D.U. Hematology and Cellular Therapy, A.O. Ord. Mauriziano-Umberto I, Turin, Italy

    C Tarella & A Gueli

  5. Department of Hematology, A.O. S. Giovanni Battista Molinette, Turin, Italy

    L Bergui

  6. Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy

    L Trentin & A Barzan

  7. Department of Hematology, Policlinico GB Rossi, Verona, Italy

    F Benedetti & A Ambrosetti

  8. Division of Hematology, Ospedale Ferrarotto, AOU Policlinico-OVE, University of Catania, Catania, Italy

    F Di Raimondo & A Chiarenza

  9. Division of Internal Medicine and Haematology, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

    G Parvis

  10. Hematology Department, San Maurizio Regional Hospital, Bolzano, Italy

    A Billio

  11. Division of Haematology, Ospedale San Carlo, Potenza, Italy

    I Attolico & A Olivieri

  12. Division of Haematology, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy

    M Montanari

  13. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan, Italy

    C Carlo-Stella

  14. Chair of Oncology, University of Milan, Milan, Italy

    C Carlo-Stella & A M Gianni

  15. Fondazione Michelangelo, Milan, Italy

    P Valagussa

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  1. M Magni
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  20. I Attolico
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Correspondence to M Magni.

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Magni, M., Nicola, M., Patti, C. et al. Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis. Bone Marrow Transplant 49, 485–491 (2014). https://doi.org/10.1038/bmt.2013.214

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  • DOI: https://doi.org/10.1038/bmt.2013.214

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