High-dose yttrium-90-ibritumomab tiuxetan with tandem stem-cell reinfusion : an outpatient preparative regimen for autologous hematopoietic cell transplantation

Purpose: To develop high-dose myeloablative therapy for CD20+ non-Hodgkin's lymphoma (NHL) as a safe and widely applicable regimen. Patients and Methods: Patients with relapsed/refractory (n = 25) or de novo high-risk (n = 5) NHL received one myeloablative dose of yttrium-90 (90Y)- ibritumomab tiuxetan after five chemotherapy courses, including three cycles of anthracycline- or platinum-containing regimens, one cycle of cyclophosphamide (4 to 7 g/m2), and one cycle of cytarabine (12 to 24 g/m2). The only exclusion criteria were CNS lymphoma and Eastern Cooperative Oncology Group performance status of more than 3. Primary end points were overall survival (OS) and event-free survival (EFS). Secondary end points included safety and applicability of high-dose 90Y-ibritumomab tiuxetan. To minimize hematologic toxicity, stem cells were reinfused at days 7 and 14 after 90Y-ibritumomab tiuxetan. Results: Thirteen patients received 90Y-ibritumomab tiuxetan 0.8 mCi/kg, and 17 patients received 1.2 mCi/kg. At 1.2 mCi/kg, the radiation absorbed by critical nonhematologic organs approached the protocol-defined upper safety limit, defining this as the recommended dose for subsequent studies. Hematologic toxicity was mild to moderate and of short duration. Infections occurred in 27% of patients (none had a severity grade greater than 3). After a median observation time of 30 months (range, 22 to 48 months), no myeloid secondary malignancy or chromosomal abnormality was observed, the OS rate was 87%, and the EFS rate was 69%. Conclusion: High-dose 90Y-ibritumomab tiuxetan seems to be an innovative myeloablative regimen with unprecedented short-term toxicity and wide applicability. Further studies are required to assess its long-term safety and role in the management of CD20+ NHL.