We previously reported feasibility and efficacy of a monocentric pilot study of intensive sequential chemotherapy (ISC) in poor-risk aggressive non-Hodgkin's lymphoma (NHL) in patients < 60 years. To validate these results on a large cohort of patients, we designed a new and oligocentric study. After a COP (cyclophosphamide (Cy), vincristine (Vcr), prednisone (Pred) debulking, patients received four courses of high-dose CHOP (Cy, doxorubicin (Doxo), Ver, Pred), with the addition of etoposide and cisplatin during the two last courses. G-CSF was delivered after each cycle, and peripheral blood stem cells (PBSC) were used to support the two last cycles. Total duration of chemotherapy was 13 weeks, with a planned dose-intensity (DI) of 1420 mg/m2/week and 23 mg/m2/week for Cy and Doxo, respectively. Radiotherapy (involved fields) was then delivered for patients with node size > or = 5 cm at diagnosis. Forty-two patients were enrolled in this study; 36 completed the treatment and received 75% or more of the planned DI for both Cy and Doxo. Median duration of grade 4 neutropenia was 14 days (range, 2 to 28) for the regimen as a whole, and median duration of rehospitalization for febrile neutropenia was 18 days (range, 4 to 41). Overall response rate was 83%, with 29 patients (69%) in complete response (CR). Six patients failed to respond and one died of toxicity. With a median follow-up of 22.5 months (range, 10 to 42), the 3-year event-free survival (EFS) is 55% (95% CI, 39-71), while disease-free survival (DFS) is 79% (95% CI, 63-95). Ambulatory ISC is accessible and feasible in an oligocentric study. PBSC allow repeated delivery of high-dose chemotherapy cycles, and result in encouraging CR, EFS, and DFS rates for poor-risk aggressive NHL's patients.