title: 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.
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.
  
  
  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.
authors: SC Ematologia II, Azienda Ospedaliera e Universitaria San Giovanni Battista, Corso Bramante 88, Turin, Italy. uvitolo@molinette.piemonte.it
authors: Umberto
authors: U
authors: Vitolo
authors: Annalisa
authors: A
authors: Chiappella
authors: Emanuele
authors: E
authors: Angelucci
authors: Giuseppe
authors: G
authors: Rossi
authors: Anna Marina
authors: AM
authors: Liberati
authors: Maria Giuseppina
authors: MG
authors: Cabras
authors: Barbara
authors: B
authors: Botto
authors: Giovannino
authors: G
authors: Ciccone
authors: Gianluca
authors: G
authors: Gaidano
authors: Lorenzo
authors: L
authors: Falchi
authors: Roberto
authors: R
authors: Freilone
authors: Domenico
authors: D
authors: Novero
authors: Lorella
authors: L
authors: Orsucci
authors: Vincenzo
authors: V
authors: Pavone
authors: Enrico
authors: E
authors: Pogliani
authors: Delia
authors: D
authors: Rota-Scalabrini
authors: Flavia
authors: F
authors: Salvi
authors: Anna
authors: A
authors: Tonso
authors: Alessandra
authors: A
authors: Tucci
authors: Alessandro
authors: A
authors: Levis
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab