Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.
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.
Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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Magni
Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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Di Nicola
Department of Hematology I, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
C
C
Patti
Department of Hematology I, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
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R
Scimè
Department of Hematology I, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
A
A
Mulè
Unit of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy.
A
A
Rambaldi
Unit of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy.
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Intermesoli
Unit of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy.
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Viero
S.C.D.U. Hematology and Cellular Therapy, A.O. Ord. Mauriziano-Umberto I, Turin, Italy.
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Tarella
S.C.D.U. Hematology and Cellular Therapy, A.O. Ord. Mauriziano-Umberto I, Turin, Italy.
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A
Gueli
Department of Hematology, A.O. S. Giovanni Battista Molinette, Turin, Italy.
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Bergui
Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
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Trentin
Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
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A
Barzan
Department of Hematology, Policlinico GB Rossi, Verona, Italy.
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F
Benedetti
Department of Hematology, Policlinico GB Rossi, Verona, Italy.
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A
Ambrosetti
Division of Hematology, Ospedale Ferrarotto, AOU Policlinico-OVE, University of Catania, Catania, Italy.
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Di Raimondo
Division of Hematology, Ospedale Ferrarotto, AOU Policlinico-OVE, University of Catania, Catania, Italy.
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A
Chiarenza
Division of Internal Medicine and Haematology, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
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Parvis
Hematology Department, San Maurizio Regional Hospital, Bolzano, Italy.
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A
Billio
Division of Haematology, Ospedale San Carlo, Potenza, Italy.
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I
Attolico
Division of Haematology, Ospedale San Carlo, Potenza, Italy.
A
A
Olivieri
Division of Haematology, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
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Montanari
1] Medical Oncology and Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan, Italy [2] Chair of Oncology, University of Milan, Milan, Italy.
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0000000331440124
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Carlo-Stella
Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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Matteucci
Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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L
Devizzi
Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
A
A
Guidetti
Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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S
Viviani
Fondazione Michelangelo, Milan, Italy.
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P
Valagussa
1] Division of Medical Oncology, Bone Marrow Transplantation Unit, Fondazione IRCCS, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy [2] Chair of Oncology, University of Milan, Milan, Italy.
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Gianni
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D000069283:Rituximab; D014182:Transplantation, Autologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014750:Vincristine / Q000008:administration & dosage
D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D011241:Prednisone