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 Resea rch and Treatment of Cancer Lymphoma Group designed a prospective randomize d trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy impro ves 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 bleomyc in and vincristine added at mid-cycle). After these three cycles, patients With a complete or partial remission and at that time no lymphoma involveme nt in the bone marrow were randomly assigned to the ABMT arm (a further thr ee cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to t he control arm (five more cycles: of CHVVmP/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-inte rmediate International Prognostic Index (IPI) risk. After a median follow-u p of 53 months, an intention-to-treat analysis' Showed a time to disease pr ogression 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 ABM T arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respecti vely, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for r eliable statistical analysis, yielded similar results. Conclusions: Standar d combination therapies remain the best choice for most patients with aggre ssive NHL, We recommend that patients,vith IPI low or low-intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therap y.