COMPARISON OF CHOP CHEMOTHERAPY WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR SLOWLY RESPONDING PATIENTS WITH AGGRESSIVE NON-HODGKINS-LYMPHOMA

Background. High-dose chemoradiotherapy combined with autologous bone marrow transplantation can cure patients with disseminated, aggressive non-Hodgkin's lymphoma in whom first-line chemotherapy has failed. In contrast, cure is rare with second-line chemotherapy. It has been sug gested that patients with slow responses to the initial phase of first -line chemotherapy are at high risk for relapse. Therefore, such patie nts are potential candidates for early bone marrow transplantation. Me thods. To investigate whether patients with slow responses, defined as only a partial response after three courses of cyclophosphamide, doxo rubicin, vincristine, and prednisone (CHOP), would benefit from early transplantation, we conducted a prospective, randomized trial. The ear ly application of high-dose chemoradiotherapy and autologous bone marr ow transplantation was compared with the continuation of CHOP therapy for another five courses. Patients with complete responses after three courses of CHOP (fast responses) and patients who responded partially but still had tumor-positive marrow continued with another five cours es of CHOP. The study end points were the response rate, overall survi val, disease-free survival, and event-free survival. Results. Of 286 p atients who could be evaluated for the rapidity of their response afte r three courses of CHOP, 38 percent had fast responses, 47 percent had slow responses, and 15 percent had no response. Among 106 patients wi th slow responses who had lymphoma-negative marrow, 69 patients (65 pe rcent) were randomized. Seventy-four percent of the CHOP group and 68 percent of the transplantation group had complete remissions (P=0.54). At four years the rates of overall, disease-free, and event-free surv ival were 85, 72, and 53 percent, respectively, in the CHOP group and 56, 60 and 41 percent in the transplantation group (P>0.10). The disea se-free survival in both groups did not differ significantly from that of nonrandomized patients with fast responses (54 percent at four yea rs). Conclusions. The early application of high-dose, marrow-ablative chemoradiotherapy with autologous bone marrow transplantation does not improve the outcome in patients with aggressive non-Hodgkin's lymphom a that responds slowly to first-line CHOP chemotherapy.