Published online 7 July 2009
Haematologica, Vol 94, Issue 9, 1250-1258 doi:10.3324/haematol.2009.007005
Copyright © 2009 by Ferrata Storti Foundation
Umberto Vitolo1 ,
Annalisa Chiappella1 ,
Emanuele Angelucci2 ,
Giuseppe Rossi3 ,
Anna Marina Liberati4 ,
Maria Giuseppina Cabras2 ,
Barbara Botto1 ,
Giovannino Ciccone5 ,
Gianluca Gaidano6 ,
Lorenzo Falchi4 ,
Roberto Freilone1 ,
Domenico Novero7 ,
Lorella Orsucci1 ,
Vincenzo Pavone8 ,
Enrico Pogliani9 ,
Delia Rota-Scalabrini10 ,
Flavia Salvi11 ,
Anna Tonso12 ,
Alessandra Tucci3 ,
Alessandro Levis11 on behalf of Gruppo Italiano Multiregionale Linfomi e Leucemie (GIMURELL)
Haematologica, Vol 94, Issue 9, 1250-1258 doi:10.3324/haematol.2009.007005
Copyright © 2009 by Ferrata Storti Foundation
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Malignant Lymphomas |
Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study
1 SC Ematologia II, Azienda Ospedaliera e Universitaria San Giovanni Battista, Torino
2 SC Ematologia, Ospedale Oncologico di Riferimento Regionale Armando Businco, Cagliari
3 Divisione di Ematologia, ASO Spedali Civili, Brescia
4 Divisione di Clinica Medica, Policlinico Monteluce, Perugia
5 SCDU Epidemiologia dei Tumori, Azienda Ospedaliera e Universitaria San Giovanni Battista, CPO Piemonte, Torino
6 Divisione di Ematologia, Università del Piemonte Orientale Amedeo Avogadro, Novara
7 Servizio di Anatomia Patologica, Azienda Ospedaliera e Universitaria San Giovanni Battista, Università degli Studi, Torino
8 Cattedra di Ematologia, Policlinico, Bari
9 Divisione Universitaria di Ematologia, ASO S. Gerardo de’ Tintori, Monza
10 Divisione di Oncoematologia, Istituto per la Ricerca e la Cura del Cancro IRCC, Candiolo
11 Divisione di Ematologia, ASO SS Antonio e Biagio e Cesare Arrigo, Alessandria
12 Divisione di Medicina B, Ospedale degli Infermi, Biella, Italy
Correspondence: Umberto Vitolo, MD, S.C. Ematologia 2, Azienda Ospedaliera S. Giovanni Battista, Corso Bramante 88, 10126 Torino, Italy. E-mail:uvitolo{at}molinette.piemonte.it
Background: We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma.
Design and Methods: Ninety-four young patients (age, 18–60) with stage III–IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan (BEAM) with autologous stem cell transplantation.
Results: The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexate-doxorubicin-cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-free survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox’s multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival.
Conclusions: These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials.
Key words: diffuse large B-cell lymphoma, autologous stem cell transplantation, dose-dense chemotherapy, rituximab, poor prognosis, high-dose chemotherapy.
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