Tandem autologous transplant actually represents a challenge in multiple myeloma treatment, but the best conditioning regimen is still under investigation. With the aim of evaluating the feasibility of a modified tandem transplant strategy, we treated 10 multiple myeloma patients after conventional first line chemotherapy with a two step conditioning regimen consisting of high-dose melphalan (200 mg/m2) followed by high-dose melphalan (180 mg/m2) together with indarubicin (15 mg/sqm2 c.i. x 3 days) both with peripheral stem cell support. At first transplant, the median age wasyears, performance status was good and disease status was CR in 2 patients and PR in the rest. At the end of the first transplant, 70% of patients achieved CR and only mild toxicity was observed. After the second transplant further improvement of the response rate was obtained with 90% CR. However, we observed three toxic early infection-related deaths from CMV and legionella pneumonia at day + 17, +26, +54 after transplantation. Although this schedule seems to be effective in terms of response rate, the 30% TRM imposes an anthracycline dose-reduction with careful patient selection. This approach could reduce the toxic effects and maintain the efficacy of therapy at the same time.