Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial.
OBJECTIVE
To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin's lymphoma (NHL).


METHODS
We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease.


RESULTS
The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P =.95), 5-year progression-free survival was 49% and 61% (P =.21), and 5-year relapse-free survival was 65% and 77% (P =.22), respectively.


CONCLUSIONS
Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.
Martelli
Maurizio
M
Department of Cellular Biotechnology and Hematology, University La Sapienza of Rome, Italy. martelli@bce.med.uniroma1.it
Gherlinzoni
Filippo
F
De Renzo
Amalia
A
Zinzani
Pier Luigi
PL
De Vivo
Antonio
A
Cantonetti
Maria
M
Falini
Brunangelo
B
Storti
Sergio
S
Meloni
Giovanna
G
Rizzo
Manuela
M
Molinari
Anna Lia
AL
Lauria
Francesco
F
Moretti
Luciano
L
Lauta
Vito Michele
VM
Mazza
Patrizio
P
Guardigni
Luciano
L
Pescarmona
E
E
Pileri
S A
SA
Mandelli
Franco
F
Tura
Sante
S
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*
D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate