Objective: To compare the therapeutic outcome ofhigh-dose therapy (HDT) and peripheral blood progenitorcell transplantation (PBPCT) administered up-front withthe standard conventional CHOP chemotherapy in terms ofthe degree of tumor response, i.e., rate of completeresponse (CR) and progressive disease (PD) and lifethreatening toxicities, i.e., febrile neutropenia, inpatients newly diagnosed as advanced poor prognosisaggressive non-Hodgkin's lymphoma (NHL). Design: Prospective randomized controlled trial. Setting: Two tertiary-care teaching medicalcenters. Patients and methods: Patients, aged 15-55 years,who were newly diagnosed as poor prognosis (high- andhigh-intermediate risk groups according to the agedadjusted international prognostic index) aggressive NHL(category F, G, H by the Working Formulation) wereentered into the study. After three courses of CHOPtherapy, the patients were stratified randomizedaccording to age, risk-group and degree of tumorresponse to continue with CHOP therapy or receiving HDTand PBPCT. Tumor response were assesed at 4 weeks posttherapy by standard procedures. The occurrence offebrile neutropenia were measured during the study. Results: There were a total of 54 patients. Themedian age was 35.5 years (range, 1755). Male: femalewas 1.2:1. Sixty-three percent of the patients were thehigh-risk cases. Nine patients (16.7%) died during thefirst three courses of CHOP therapy and 1 patient waslost to follow-up. The remaining 44 patients wererandomized to receive CHOP (N = 22) or HDT with PBPCT(N = 22). The prognostic features were similar in the 2groups. With the intention-to-treat analysis, the rateof CR were comparable in the 2 groups (39% in the HDTvs. 38% in the CHOP therapy P = 1.00). The rate ofdisease progression however was much higher in patientswho recieved CHOP chemotherapy (0%, 95% CI, 0 - 37% inthe high-dose group vs. 40%, 95% CI, 19-64%, in theCHOP arm, P = 0.063). The rate of febrile neutropeniaand death were not significantly different in the twogroups. Among the various important clinical features,the degree of tumor response obtained after the thirdcourse of CHOP therapy was the most significantvariable predicting the therapeutic outcome. Conclusion: HDT and PBPCT reduced the risk ofdisease progression as compared to standard CHOPtherapy in patients with poor prognosis aggressive NHL.The risk of death as well as life-threateningcomplications were not increased with this high-dose treatment.