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.
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.
Fermé
Christophe
C
Groupe d'Etudes des Lymphomes de l'Adulte, Hôpital Saint-Louis, Paris, France. ferme@igr.fr
Mounier
Nicolas
N
Diviné
Marine
M
Brice
Pauline
P
Stamatoullas
Aspasia
A
Reman
Oumedaly
O
Voillat
Laurent
L
Jaubert
Jérôme
J
Lederlin
Pierre
P
Colin
Philippe
P
Berger
Françoise
F
Salles
Gilles
G
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
D003561:Cytarabine; D014747:Vinblastine; D005047:Etoposide; D008935:Mitoguazone; D008558:Melphalan; D000077235:Vinorelbine; D002330:Carmustine; D007069:Ifosfamide