ABSTRACT Background Rarioimmunotherapy (RIT) with 90-yttrium ibritumomab tiuxetan (90Y-IT) is known to be an effective approach for treatment of NHL, because lymphoma is highly radiosensitive, however, 3-year progression-free survival in our department is 39.1% (overall survival is 79.9%), which is not sufficient considering the cost-effectiveness. Consolidation therapy with RIT is another attractive approach; however, bone marrow suppression is a major and life-threatening issue for especially aged patients. In view of these findings, we employed RIT (90Y-IT) followed by HDT (LEED) in patients with relapsed and refractory B-cell lymphoma. In this report, we tried to evaluate the safety and efficacy of RIT using ibritumomab tiuxetan (Zevalin) combined with high-dose LEED chemotherapy and ASCT (Z-LEED) in refractory/relapsed B-cell lymphoma. Patients and methods Eight patients with relapsed or refractory B-cell lymphoma (three mantle cell lymphoma patients and five grade III FL/DLBCL patients) were treated with Z-LEED. After PBSC mobilization and harvesting, the minimum target dose of CD34+ cells (2 × 106/kg) was stored. Patients were 111In ibritumobab tiuxetan (185 MBq IV) on day 1, followed by 90Y-IT (14.8 MBq/kg IV] administration on day 8 after rituximab. Then high-dose chemotherapy was delivered using the LEED (500 mg/m2 etoposide on day 4, 3, and 2; 60 mg/m2 cyclophosphamide on day 4 and 3; 130 mg/m2 mephalan on day 1; and 40 mg/m2 dexamethasone on day 4, 3, 2 and 1). Results Two patients had received more than three prior treatments, and three had chemotherapy-resistant disease. There were no therapy-related deaths. While one patient with conventionally measurable disease at the time of treatment, the respective complete and overall response rates were 100%. Seven patients remain CR at 2–27 months from transplantation and 8–102 months from diagnosis. One patient relapsed after 4 months from transplantation. Conclusion ibritumomab tiuxetan combined with LEED high-dose chemotherapy is safe and possibly effective as a conditioning regimen for ASCT.