Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma.
OBJECTIVE
Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT).


METHODS
Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT.


RESULTS
Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007) and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009), bone marrow involvement (P =.003), and HDT treatment group (P =.04).


CONCLUSIONS
Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.
Gisselbrecht
Christian
C
Institut d'Hématologie, GELA Hôpital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris cedex 10, France. christian.gisselbrecht@sls.ap-hop-paris.fr
Lepage
Eric
E
Molina
Thierry
T
Quesnel
Bruno
B
Fillet
Georges
G
Lederlin
Pierre
P
Coiffier
Bertrand
B
Tilly
Hervé
H
Gabarre
Jean
J
Guilmin
Francoise
F
Hermine
Olivier
O
Reyes
Félix
F
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage; D001773:Blood Cells / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014751:Vindesine / Q000008:administration & dosage
D001761:Bleomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D014751:Vindesine; D011241:Prednisone