Comparison of up-front high-dose therapy and autologous peripheral blood progenitor cell transplantation with standard chemotherapy regimen (CHOP) in patients with poor prognosis advanced non-Hodgkin's lymphoma : a randomized controlled trial

Abstract

Objective : To compare the therapeutic outcome of high-dose therapy (HDT) and peripheral blood progenitor cell transplantation (PBPCT) administered up-front with the standard conventional CHOP chemotherapy in terms of the degree of tumor response, i.e., rate of complete response (CR) and progressive disease (PD) and life threatening toxicities, i.e., febrile neutropenia, in patients newly diagnosed as advanced poor prognosis aggressive non-Hodgkin's lymphoma (NHL). Design : Prospective randomized controlled trial. Setting : Two tertiary-care teaching medical centers. Patients and methods : Patients, aged 15-55 years, who were newly diagonosed as poor prognosis (high-and high-intermediate risk groups according to the aged adjusted international prognostic index) aggressive NHL (category F, G, H by the working formulation) were entered into the study. After three courses of CHOP therapy, the patients were stratified randomized according to age, risk-group and degree of tumor response to continue with CHOP therapy or receiving HDT and PBPCT. Tumor response were assesed at 4 weeks post therapy by standard procedures. The occurrence of febrile neutropenia were measured during the study. Results : There were a total of 54 patients. The median age was 35.5 years (range, 17-55). Male : female was 1.2:1. Sixty-three percent of the patients were the high-risk cases. Nine patients (16.7%) died during the first three courses of CHOP therapy and 1 patient was lost to follow-up. The remaining 44 patients were randomized to receive CHOP (N = 22) or HDT with PBPCT (N = 22). The prognostic features were similar in the 2 groups. With the intention-to-treat analysis, the rate of CR were comparable in the 2 groups (39% in the HDT vs. 38% in the CHOP therapy P = 1.00). The rate of disease progression however was much higher in patients who recieved CHOP chemotherapy (0%, 95% CI, 0-37% in the high-dose group vs. 40%, 95% CI, 19-64%, in the CHOP arm, P = 0.063). The rate of febrile neutropenia and death were not significantly different in the two groups. Among the various important clinical features, the degree of tumor response obtained after the third course of CHOP therapy was the most significant variable predicting the therapeutic outcome. Conclusion: HDT and PBPCT reduced the risk of disease progression as compared to standard CHOP therapy in patients with poor prognosis aggressive NHL. The risk of death as well as life-threatening complications were not increased with this high-dose treatment.