title: Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era.
abstract: OBJECTIVE
  Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown.
  
  
  METHODS
  Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT.
  
  
  RESULTS
  The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001).
  
  
  CONCLUSIONS
  In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.
authors.affiliation: Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France. christian.gisselbrecht@sls.aphp.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Devinder
authors.initials: D
authors.lastname: Singh Gill
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Marek
authors.initials: M
authors.lastname: Trneny
authors.forename: Andre
authors.initials: A
authors.lastname: Bosly
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ketterer
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Hans
authors.initials: H
authors.lastname: Hagberg
authors.forename: David
authors.initials: D
authors.lastname: Ma
authors.forename: Josette
authors.initials: J
authors.lastname: Brière
authors.forename: Craig H
authors.initials: CH
authors.lastname: Moskowitz
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005060:Europe; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007557:Israel; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009519:New York City; D016016:Proportional Hazards Models; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D003561:Cytarabine; D000069283:Rituximab; D005047:Etoposide; D003907:Dexamethasone; D016190:Carboplatin; D007069:Ifosfamide