Fourteen consecutive patients with poor-risk aggressive NHL who at presentation had any one of four risk factors underwent response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation. After treatment with three cycles of conventional CHOP with G-CSF support (CHOP-G), the response was evaluated. For patients who achieved a complete remission (CR), an additional three cycles of CHOP-G were administered, while for partial response patients, another induction regimen including some non-cross-resistant agents was given; three cycles of VIPDexa-G (etoposide, ifosfamide, cisplatinum and dexamethasone) +/- two cycles of ENAP-G (mitoxantrone, etoposide, cytosine arabinoside and prednisone), were given. The scheduled induction chemotherapy, was followed by treatment with a high-dose cytoreductive regimen followed by autologous PBPC transplantation. After three cycles of CHOP-G, four patients (29%) achieved a CR, and 10 (71%) achieved a partial response (PR). When all scheduled induction therapy was completed, 10 patients (71%) had a CR. All 14 patients received high-dose therapy and obtained a complete hematologic recovery, except for one with a bone marrow relapse two months after transplantation. Evaluation of response after high-dose therapy showed 12 CRs (86%) which included three additional CRs, one PR, and one toxicity-related death. With a median follow-up of 12 months (range, 4 to 40), 12 are alive, with 11 in continuous first CR, and one relapse. The 2-year overall survival (OS) rate and event-free survival (EFS) rate are 77% and 79%, respectively, while the disease-free survival (DFS) rate is 92%. In conclusion, this pilot study suggests that response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation is commendable and can be associated with a high rate of remission and DFS for poor risk subjects with aggressive NHL.