High Dose Therapy and Atitologous Marrow Transplantation as Salvage Treatment for Patients with Diffuse Large Cell Lymphoma zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE JAMES 0. ARMITAGE,* SUNDAR JAGANNATH,t GARY SPITZER,t PHIL BIERMAN, ANNE KEWNGER, PRADEEP KUMAR, FERNANDO CABANILLAS,t AXEL ZANDER,t LIJDA VELLEKOOPt and KAREL A. DICKEt zyxwvutsrqpon University of Nebraska Medical Center, Omaha, Nebraska, U.S.A. and Universityof Texas M.D. Amierson Hospital and Tumor Institute, Houston, Texas, U.S.A. Abstmci-Twenty-nine patients with diffuse large cell lymphoma who failed traditional chemotherapy were treated with high dose chemotherapy with or without total body irradiation followed by infusion of cryopreserved autologous marrow. Complete response was achieved in 11129 patients (38% ), partial response in 13129 patients (45% ) and 5129 patients (17%) had no response. Six complete responders remain well and free of disease for 5+, 6+, 9+, 10-k, 18 f and 25+ months, 3 relapsed at 2, 3 and 8 months after marrow infusion, and 2 diedfrom infectious complications. Complete response was seen more frequently with the absence of bulky tumor (70 us 21% , P = 0.03), a total body irradiation containing regimen (52 us O% , P = O.O3), a history of complete remission with initial chemotherapy (55% vs. 9% , P = Q.Q3), and a performance status 2 80 (56 us 15%, P = 0.06). High dose theraby had a high response rate (83% ) in resistant dtffuse large cell lymphoma andyielded durable complete responses in a minority of these patients. INTRODUCTION THE MOST common aggrcssivc non-Hodgkins’ lym- phoma is diffuse large cell lymphoma. Although highly chemotherapy responsive, the cure rate in large series with long follow-up has not excecdcd 50%. Failure to achieve a complete remission with chemotherapy, or relapse after complete remission has been achieved, almost always means eventual death from lymphoma. Salvage chemotherapy reg- imens in this disease have been disappointing with only rare reports of cures [ 11. A dose-response curve to chemotherapy has been demonstrated in a variety of tumors [2]. In addition, present cryopreservation technology has made reconstitution after reinfusion of frozen auto- logous marrow following marrow ablative therapy highly reproducible [3]. This allowed the study of dose escalation in lymphomas using agents with primarily marrow toxicity. Cures have been reg- ularly reported in relapsed Burkitt’s lymphoma with high dose therapy and autologous marrow Accepted 16 December 1985. *To whom reprint requests should be addressed at: Department of Internal Medicine, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105, U.S.A. EJC 22:7-H 871 transplantation [4]. Most reports to date of high dose therapy and autologous marrow transplanta- tion in other lymphomas have studied the feasibil- ity of the approach or looked at the use of a particular regimen while treating a mixture of histologic types [.5-241. This treatment has been reported in few patients with diffuse large cell lymphoma. We therefore reviewed all the patients with diffuse large ccl1 lymphoma treated at our institutions in studies of high dose therapy and autologous marrow transplantation to gain insight into the tumor response rate and the tolerance of these generally older patients to this very intensive treatment approach. PATIENTS AND METHODS This report presents the results of high dose therapy and autologous bone marrow transplanta- tion for all patients with de nova diffuse large ccl1 lymphoma treated by the authors at their rcspec- tive institutions through December 1984. These 29 patients were treated in a series of sequential studies utilizing different treatment regimens. Pa- tients with all histologic subtypes of lymphoma were entered into these studies. Criteria for entry included demonstrated incurability with standard