One-third of patients aged <or=60 years with aggressive lymphoma are at low-intermediate risk (LIR). Before the rituximab era, we prospectively compared ACVBP with ECVBP, a similar regimen including epirubicin instead of doxorubicin and increased dose intensity of cyclophosphamide, followed by conventional consolidation with an increased amount and dose intensity of cytosine-arabinoside, methotrexate, etoposide, and ifosfamide, in 652 patients with LIR aggressive lymphoma. The overall response rate, 5-year event-free survival (EFS), and survival were estimated to be 86%, 60%, and 74%, respectively, with no differences between the two arms. In patients with diffuse large B-cell lymphoma (DLBCL) who received ACVBP, the 5-year EFS and survival were estimated at 69% and 82%. These findings do not support the use of a chemotherapy regimen more intensive than ACVBP in patients aged <or=60 years with LIR aggressive lymphoma. The results in the control arm, without rituximab, have led to a randomized comparison of R-ACVBP and R-CHOP in this patient population.