Journal Article

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

Chiarenza, A, Benedetti, F, Tarella, C, Gianni, A M, Di Raimondo, F, Billio, A, Patti, C, Bergui, L, Mulè, A, Barzan, A, Attolico, I, Gueli, A, Magni, M, Montanari, M, Matteucci, P, Olivieri, A, Rambaldi, A, Trentin, L, Valagussa, P, Parvis, G, Scimè, R, Viero, P, Devizzi, L, Viviani, S, Carlo-Stella, C, Intermesoli, T, Nicola, M Di, Ambrosetti, A, Guidetti, A

2014

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/1904 / 692/699/67/1059/99 / 692/699/67/1990/283/1895 / Adult / Aged / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Antibodies, Monoclonal, Murine-Derived - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Autografts / Biological and medical sciences / Bone marrow / Bone marrow, stem cells transplantation. Graft versus host reaction / Cancer / Care and treatment / Cell Biology / Chemotherapy / Chronic lymphocytic leukemia / Clinical trials / Comparative analysis / Cyclophosphamide - administration & dosage / Cytarabine - administration & dosage / Doxorubicin - administration & dosage / Female / Fludarabine / Hematologic and hematopoietic diseases / Hematology / Hematopoietic Stem Cell Mobilization - methods / Hematopoietic Stem Cell Transplantation - methods / Humans / Internal Medicine / Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy / Leukemia, Lymphocytic, Chronic, B-Cell - therapy / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Lymphocytes B / Male / Medical sciences / Medicine / Medicine & Public Health / Melphalan - administration & dosage / Middle Aged / original-article / Patients / Prednisone - administration & dosage / Prospective Studies / Public Health / Rituximab / Stem cell transplantation / Stem Cells / Subgroups / Survival / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transplantation / Transplantation, Autologous / Vidarabine - administration & dosage / Vidarabine - analogs & derivatives / Vincristine - administration & dosage