title: A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma.
abstract: BACKGROUND
  High-dose chemotherapy combined with autologous stem-cell transplantation (ASCT) is the standard therapy for refractory/relapsed aggressive lymphoma. In the era of rituximab-containing frontline regimens, it is becoming more challenging to salvage patients in this setting, and novel approaches are required. This is a randomized study evaluating the safety and efficacy of standard-dose ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy (Z-BEAM) and ASCT in refractory/relapsed aggressive lymphoma.
  
  
  METHODS
  Forty-three patients with CD20(+) -aggressive lymphoma were randomized to a treatment arm (Z-BEAM, n = 22) or control arm (BEAM alone, n = 21). Ibritumomab tiuxetan was given at 0.4 mCi/kg on day -14 before ASCT.
  
  
  RESULTS
  Patient characteristics, engraftment kinetics, and toxicity profile were similar between the 2 groups. Two-year progression-free survival (PFS) for all patients was 48% (95% confidence interval, 32%-64%): 59% and 37% after Z-BEAM and BEAM alone, respectively (P = .2). Multivariate analysis identified advanced age (hazard ratio [HR], 8.3; P = .001), high-risk disease (relapse within 12 months of diagnosis and/or secondary International Prognostic Index >2; HR, 2.8; P = .04), positive positron emission tomography-computed tomography pretransplant (HR, 2.4; P = .07), and BEAM alone (HR, 2.8; P = .03) as poor prognostic factors. Intermediate-risk patients with 1 or 2 risk factors had better PFS with Z-BEAM compared with BEAM: 69% and 29%, respectively (P = .07). Two-year overall survival was 91% and 62% after Z-BEAM and BEAM, respectively (P = .05). Similar prognostic factors determined survival. The HR for BEAM alone in the multivariate analysis was 8.1 (P = .01).
  
  
  CONCLUSIONS
  Standard-dose ibritumomab tiuxetan combined with BEAM high-dose chemotherapy is safe and possibly more effective than BEAM alone as a conditioning regimen for ASCT in the era of rituximab-containing chemotherapy regimens.
authors.affiliation: Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel. ashimoni@sheba.health.gov.il
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Moshe
authors.initials: M
authors.lastname: Yeshurun
authors.forename: Itai
authors.initials: I
authors.lastname: Levi
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.forename: Paulina
authors.initials: P
authors.lastname: Patachenko
authors.forename: Abraham
authors.initials: A
authors.lastname: Avigdor
authors.forename: Tzila
authors.initials: T
authors.lastname: Zwas
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D018401:Sample Size; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D003561:Cytarabine; C422802:ibritumomab tiuxetan; D005047:Etoposide; D008558:Melphalan; D002330:Carmustine