Originally published as JCO Early Release 10.1200/JCO.2008.16.8294 on October 14 2008

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High-Dose Yttrium-90–Ibritumomab Tiuxetan With Tandem Stem-Cell Reinfusion: An Outpatient Preparative Regimen for Autologous Hematopoietic Cell Transplantation

Liliana Devizzi, Anna Guidetti, Corrado Tarella, Michele Magni, Paola Matteucci, Ettore Seregni, Carlo Chiesa, Emilio Bombardieri, Massimo Di Nicola, Carmelo Carlo-Stella, Alessandro M. Gianni

From the "Cristina Gandini" Medical Oncology and Department of Nuclear Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori; Department of Medical Oncology, University of Milano, Milano; and Department of Hematology, Ospedale Molinette, University of Torino, Torino, Italy

Corresponding author: Alessandro M. Gianni, MD, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy; e-mail: alessandro.gianni{at}unimi.it

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.

published online ahead of print at www.jco.org on October 13, 2008.

Supported in part by grants from Ministero dell'Università e della Ricerca (Rome, Italy), Ministero della Salute (Rome, Italy), Alleanza Contro il Cancro (Rome, Italy), and Michelangelo Foundation for Advances in Cancer Research and Treatment (Milano, Italy).

L.D. and A.G. contributed equally to this work.

Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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