Patients with chemosensitive aggressive non-Hodgkin lymphoma (NHL) could benefit from high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (auto-SCT). We report clinical outcomes of HDC using a novel regimen consisting of mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) with auto-SCT. A total of 69 patients were consecutively enrolled. Median age was 42 years (range, 20-66 years). Median event-free survival (EFS) was 17.9 months. Median overall survival (OS) has not been reached yet and estimated 2-year OS was 64.2%. Among patients with measurable lesions, response rate was 79.5%. Median time to recovery of neutrophil (>500 mL) and platelet (gt;20,000 mL) was 12.5 and 13.5 days, respectively. Febrile neutropenia developed in 61 patients (88.4%). Grades 3 or 4 hepatic toxicity developed in 7 patients (10.1%), Grades 3 or 4 renal toxicity in 2 patients (2.9%), and Grade 3 or 4 cardiac toxicity in 2 patients (2.9%). Transplant-related mortality (TRM) developed in two patients (2.9%). Multiple prior treatments before transplantation, auxiliary bone marrow harvest for stem cell collection, and high serum lactate dehydrogenase level were related to unfavorable treatment outcomes. In conclusion, NEAM conditioning with auto-SCT demonstrated considerable efficacy with modest toxicity in patients with chemosensitive aggressive NHL.