Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.
OBJECTIVE
This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.


METHODS
Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged <or= 60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997. Patients with at least a minor response after two cycles of CHOEP (CHOP + etoposide 3 x 100 mg/m(2)) were to receive three further cycles of CHOEP followed by IF radiotherapy (arm A) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy (arm B).


RESULTS
Among 158 patients randomized to arm B, 103 (65%) received HDT. The complete remission rate at the end of treatment was 62.9% in arm A and 69.9% in arm B. With a median observation time of 45.5 months, overall survival for all 312 patients was 63% after 3 years (63% for arm A, 62% for arm B; P =.68). Event-free survival was 49% for arm A versus 59% for arm B (P =.22). Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A (P <.05). Relapse after HDT occurred early (median interval, 3 months). Six patients developed secondary neoplasia, three in arm A and three in arm B.


CONCLUSIONS
Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.
Kaiser
Ulrich
U
Department of Hematology, Universitätsklinikum Marburg, Germany. pd.dr.u.kaiser@bernward-khs.de
Uebelacker
Irmgard
I
Abel
Ulrich
U
Birkmann
Josef
J
Trümper
Lorenz
L
Schmalenberg
Harald
H
Karakas
Tunca
T
Metzner
Bernd
B
Hossfeld
Dieter K
DK
Bischoff
Helge G
HG
Franke
Astrid
A
Reiser
Marcel
M
Müller
Peter
P
Mantovani
Luisa
L
Grundeis
Marc
M
Rothmann
Frank
F
von Seydewitz
Cay-Uwe
CU
Mesters
Rolf M
RM
Steinhauer
Ernst U
EU
Krahl
Dorothea
D
Schumacher
Kurt
K
Kneba
Michael
M
Baudis
Michael
M
Schmitz
Norbert
N
Pfab
Rüdiger
R
Köppler
Hubert
H
Parwaresch
Reza
R
Pfreundschuh
Michael
M
Havemann
Klaus
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005858:Germany; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000201:enzymology* / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012306:Risk; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D007770:L-Lactate Dehydrogenase; D008558:Melphalan; D002330:Carmustine