Induction treatment with SMILE and consolidation with autologous stem cell transplantation for newly diagnosed stage IV extranodal natural killer/T-cell lymphoma patients.

The aim of this study was to investigate the impact of the induction treatment with SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy and consolidation with upfront autologous stem cell transplantation (ASCT) on clinical outcomes of patients with stage IV extranodal natural killer/T-cell lymphoma (ENKTL). We analyzed the treatment response to SMILE and toxicity, and explored the feasibility of upfront ASCT in 27 patients with stage IV ENKTL out of patients who were enrolled into our prospective cohort studies. The median age of patients was 45 years (range: 17-65 years), and all patients had disseminated disease. The overall response rate to SMILE induction treatment was 59 % (16/27) including nine complete responses. However, five patients died due to grade IV febrile neutropenia during SMILE and six patients did not respond to SMILE. Eleven patients could undergo ASCT, and there was no transplantation-related mortality. The survival outcome of patients underwent ASCT was better than patients who could not (P < 0.05). However, four patients relapsed even after ASCT, thus, the median overall survival was 10.6 months, and the median progression-free survival was 5.1 months. Pretreatment Epstein-Barr virus (EBV) DNA titer was only independent prognostic factor for overall survival. In conclusion, our results suggest SMILE followed by ASCT might be an effective treatment strategy for stage IV ENKTL. However, considering frequent occurrences of disease relapse and treatment-related mortality, additional efforts are required to improve treatment outcomes of stage IV ENKTL patients.