title: Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial.
abstract: OBJECTIVE
  To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment.
  
  
  METHODS
  Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT.
  
  
  RESULTS
  With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival.
  
  
  CONCLUSIONS
  Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.
authors.affiliation: Groupe d'Etudes des Lymphomes de l'Adulte, Hôpital Saint-Louis, Paris, France. ferme@igr.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Fermé
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Marine
authors.initials: M
authors.lastname: Diviné
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Laurent
authors.initials: L
authors.lastname: Voillat
authors.forename: Jérôme
authors.initials: J
authors.lastname: Jaubert
authors.forename: Pierre
authors.initials: P
authors.lastname: Lederlin
authors.forename: Philippe
authors.initials: P
authors.lastname: Colin
authors.forename: Françoise
authors.initials: F
authors.lastname: Berger
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008935:Mitoguazone / Q000008:administration & dosage; D012008:Recurrence; D016879:Salvage Therapy; D014182:Transplantation, Autologous; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D003561:Cytarabine; D014747:Vinblastine; D005047:Etoposide; D008935:Mitoguazone; D008558:Melphalan; D000077235:Vinorelbine; D002330:Carmustine; D007069:Ifosfamide