In spite of high-dose chemotherapy followed by autologous hematopoietic SCT multiple myeloma (MM) eventually recurs, highlighting the need for more effective treatment approaches. Patients received topotecan 3.5 mg/m(2) intravenously on days -6 to -2, melphalan 70 mg/m(2) intravenously on days -3 and -2 and CY 1 g/m(2) intravenously on days -6, -5 and -4. Overall response rate (ORR) consisting of complete response and partial response (CR+PR, PFS, OS and toxicity are reported. Between August 2002 to March 2004, 60 patients (34 men and 26 women) with a median age of 61 years (range 45-72) were enrolled. Forty-one patients were treated for consolidation of first remission, while 19 patients had relapsed/refractory disease. ORR was 85% (CR 12%, very good PR 43% and PR 30%). Median time to neutrophil (ANC>0.5 × 10(9)/L) and plt engraftment (>20 × 10(9)/L) was 10 (range 7-12 days) and 9 days (range 6-79 days), respectively. A majority of the common adverse events were grade 1-3 mucositis/stomatitis (65%), grade 1 or 2 nausea (59%) and grade 1 or 2 diarrhea (41%). Median PFS was 18.5 months and median OS has yet not been reached. In conclusion, topotecan, melphalan and CY is a safe and active conditioning regimen for auto hematopoietic SCT in MM. The ORR and PFS were comparable to high-dose melphalan.