Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma

Background: Patients with Hodgkin's disease (HD) and intermediate or high-grade non-Hodghin's lymphoma (NHL) who fail to achieve a complete remission (CR) with standard induction therapy have a poor prognosis with conventional dose salvage therapy alone. We examined the role of subsequent intensive therapy and autologous bone marrow transplantation (ABMT) in patients who demonstrated a response to conventional-dose salvage therapy. Patients and methods: Sixty-six patients with either HD (n = 30) or NHL (n = 36) underwent intensive therapy with etoposide (60 mg/kg), intravenous melphalan (160-180 mg/m²) followed by infusion of unpurged autologous bone marrow and/or blood cells. All patients had advanced stage or bulky disease at diagnosis and failed to achieve a CR after an anthracycline-containing front-line chemotherapy regimen (NHL) or ABVD or equivalent regimen (HD). Patients who achieved a CR after involved-field radiotherapy were excluded. All patients demonstrated sensitivity to conventional dose salvage treatment before advancing to intensive therapy and ABMT. Resulst: The CR, partial response (PR) and overall response rate (RR) following ABMT for HD patients was 48%, 17% and 65%, respectively. At a median follow-up of 35 months, the predicted three-year overall survival (OS) is 51% (95% CI: 44%-60%) and event-free survival (EFS) is 34% (95% CI: 26%-54%). For patients with NHL, the CR, PR and RR were 68%, 9% and 77%, respectively. At a median follow-up of 28 months, the predicted three-year CS is 51% (95% CI: 35%-66%) and EFS is 39% (95% CI: 21%-57%). Conclusions: Intensive therapy with etoposide and melphalan followed by ABMT results in prolonged survival in selected patients with lymphoma who fail to achieve a complete remission to front-line chemotherapy. Based on our previous studies of outcome to conventional-dose salvage chemotherapy, we estimate that of all patients failing induction therapy, 28% with HD and 15% with NHL will be event-free at three years after ABMT.