1. 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
- Author
-
Vitolo, U, Chiappella, A, Angelucci, E, Rossi, G, Liberati, Anna Marina, Cabras, Mg, Botto, B, Ciccone, G, Gaidano, G, Falchi, L, Freilone, R, Novero, D, Orsucci, L, Pavone, V, Pogliani, E, Rota Scalabrini, D, Salvi, F, Tonso, A, Tucci, A, Levis, A, Leucemie, Gruppo Italiano Multiregionale Linfomi e., Vitolo, U, Chiappella, A, Angelucci, E, Rossi, G, Liberati, A, Cabras, M, Botto, B, Ciccone, G, Gaidano, G, Falchi, L, Freilone, R, Novero, D, Orsucci, L, Pavone, V, Pogliani, E, Rota Scalabrini, D, Salvi, F, Tonso, A, Tucci, A, and Levis, A
- Subjects
Oncology ,Male ,Adult ,dose-dense chemotherapy ,medicine.medical_specialty ,Time Factors ,autologous stem cell transplantation ,Dose-dense chemotherapy ,Adolescent ,Time Factor ,diffuse large B-cell lymphoma ,Transplantation, Autologous ,Disease-Free Survival ,Antibodies, Monoclonal, Murine-Derived ,rituximab ,Autologous stem-cell transplantation ,International Prognostic Index ,immune system diseases ,Chemoimmunotherapy ,MED/15 - MALATTIE DEL SANGUE ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Survival rate ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,poor prognosis ,high-dose chemotherapy ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Transplantation ,Survival Rate ,Transplantation, Autologou ,Original Article ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,medicine.drug ,Human ,Stem Cell Transplantation - Abstract
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.
- Published
- 2009