title: Treatment of indolent B-Cell nonfollicular lymphomas: final results of the LL01 randomized trial of the Gruppo Italiano per lo Studio dei Linfomi.
abstract: OBJECTIVE
  To evaluate the effect of epirubicin on therapeutic response and survival in patients with indolent nonfollicular B-cell lymphomas (INFL) treated with pulsed high-dose chlorambucil.
  
  
  METHODS
  A total of 170 untreated patients with advanced/active INFL were randomly assigned to receive either eight cycles of high-dose chlorambucil (15 mg/m2/d) plus prednisone (100 mg/d) for 5 days (HD-CHL-P; arm A) or eight cycles of HD-CHL-P plus epirubicin 60 mg/m2 intravenous on day 1 (arm B). The responding patients were randomly assigned to either maintenance therapy with interferon alfa (IFNalpha-2a; 3 MU, three times weekly) for 12 months or observation.
  
  
  RESULTS
  There were 160 assessable patients (82 males, 78 females; median age, 63 years; range, 33 to 77 years); 77 patients were assigned to arm A, and 83 were assigned to arm B. Induction therapy led to 47 complete responses (CRs; 29.4%) and 68 partial responses (PRs; 42.5%), with no significant difference between the two arms (60 CR + PR in arm A [77.9%] and 55 CR + PR in arm B [66.3%]; P =.07). After a median follow-up of 38 months (range, 2 to 103 months), there was no between-group difference in overall survival (OS; P =.45), failure-free survival (P =.07), or progression-free survival (PFS; P =.5). Eighty-eight patients were randomly assigned to either IFNalpha-2a (n = 43) or observation (n = 45), without any difference in 3-year PFS (44% and 42%, respectively). Univariate analysis showed that OS was influenced by age, anemia, serum lactate dehydrogenase levels, and International Prognostic Index distribution; multivariate analysis identified age and anemia as having influence on OS.
  
  
  CONCLUSIONS
  HD-CHL-P treatment outcome in INFL patients was good (50% 3-year PFS, minimal toxicity, and low costs); epirubicin did not add any advantage. One-year IFNalpha maintenance treatment did not prolong response duration.
authors.affiliation: Unità Operativa Ematologia 1, Centro G. Marcora, Ospedale Maggiore, IRCCS, Via F. Sforza 35, 20121 Milano, Italy. lubaldini@policlinico.mi.it
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Maura
authors.initials: M
authors.lastname: Brugiatelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.forename: Marco
authors.initials: M
authors.lastname: Lombardo
authors.forename: Francesco
authors.initials: F
authors.lastname: Merli
authors.forename: Stefano
authors.initials: S
authors.lastname: Sacchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gobbi
authors.forename: Marina
authors.initials: M
authors.lastname: Liberati
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavanna
authors.forename: Mariangela
authors.initials: M
authors.lastname: Colombi
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Maria
authors.initials: M
authors.lastname: Goldaniga
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Vittorio
authors.initials: V
authors.lastname: Silingardi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002699:Chlorambucil; D015251:Epirubicin; D011241:Prednisone