title: Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial.
abstract: OBJECTIVE
  To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease.
  
  
  RESULTS
  The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P =.95), 5-year progression-free survival was 49% and 61% (P =.21), and 5-year relapse-free survival was 65% and 77% (P =.22), respectively.
  
  
  CONCLUSIONS
  Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.
authors.affiliation: Department of Cellular Biotechnology and Hematology, University La Sapienza of Rome, Italy. martelli@bce.med.uniroma1.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Gherlinzoni
authors.forename: Amalia
authors.initials: A
authors.lastname: De Renzo
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Antonio
authors.initials: A
authors.lastname: De Vivo
authors.forename: Maria
authors.initials: M
authors.lastname: Cantonetti
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Sergio
authors.initials: S
authors.lastname: Storti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Meloni
authors.forename: Manuela
authors.initials: M
authors.lastname: Rizzo
authors.forename: Anna Lia
authors.initials: AL
authors.lastname: Molinari
authors.forename: Francesco
authors.initials: F
authors.lastname: Lauria
authors.forename: Luciano
authors.initials: L
authors.lastname: Moretti
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Lauta
authors.forename: Patrizio
authors.initials: P
authors.lastname: Mazza
authors.forename: Luciano
authors.initials: L
authors.lastname: Guardigni
authors.forename: E
authors.initials: E
authors.lastname: Pescarmona
authors.forename: S A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate