Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study.
BACKGROUND
The long-term outcome for patients with aggressive non-Hodgkin's lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival.


METHODS
Patients aged 15-65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). All statistical tests are two-sided.


RESULTS
From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low-intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results.


CONCLUSIONS
Standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.
Kluin-Nelemans
H C
HC
Department of Hematology, Leiden University Medical Center, The Netherlands. J.C.Kluin-Nelemans@int.azg.nl
Zagonel
V
V
Anastasopoulou
A
A
Bron
D
D
Roozendaal
K J
KJ
Noordijk
E M
EM
Musson
H
H
Teodorovic
I
I
Maes
B
B
Carbone
A
A
Carde
P
P
Thomas
J
J
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002423:Cause of Death; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D013713:Teniposide / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D013713:Teniposide; D011241:Prednisone