Originally published as JCO Early Release 10.1200/JCO.2006.09.2882 on August 20 2007

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Treatment-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Patients Treated With Ibritumomab Tiuxetan Radioimmunotherapy

Myron S. Czuczman, Christos Emmanouilides, Mohamed Darif, Thomas E. Witzig, Leo I. Gordon, Stephen Revell, Katie Vo, Arturo Molina

From the Roswell Park Cancer Institute, Buffalo, NY; University of California, Los Angeles; Biogen Idec, San Diego, CA; Mayo Clinic, Rochester, MN; and Northwestern University, Chicago, IL

Address reprint requests to Myron S. Czuczman, MD, Roswell Park Cancer Institute, Elm & Carlton St, Buffalo, NY 14263; e-mail: Myron.Czuczman{at}RoswellPark.org

Purpose To investigate the incidence of treatment-related myelodysplastic syndrome (t-MDS) and treatment-related acute myelogenous leukemia (t-AML) after treatment with ibritumomab tiuxetan radioimmunotherapy.

Patients and Methods Analysis of the incidence of t-MDS and t-AML in 746 patients with non-Hodgkin's lymphoma (NHL) treated with the ibritumomab tiuxetan regimen in registration and compassionate-use trials between 1996 and 2002.

Results Nineteen patients (2.5%) developed t-MDS or t-AML at a median follow-up of 4.4 years (range, 0 to 9.3). These malignancies were diagnosed at a median of 5.6 years (range, 1.4 to 13.9) after the diagnosis of NHL and 1.9 years (range, 0.4 to 6.3) after radioimmunotherapy. The annualized rates were 0.3% per year after the diagnosis of NHL and 0.7% per year after treatment. Most patients with t-MDS or t-AML had multiple cytogenetic aberrations, commonly on chromosomes 5 and 7, suggesting an association with previous exposure to chemotherapy.

Conclusion Analysis of data from patients in registration and compassionate-use trials suggests that the annualized incidences of t-MDS and t-AML are consistent with that expected in patients with NHL who have had extensive previous chemotherapy treatment and do not appear to be increased after treatment with the ibritumomab tiuxetan regimen. Cytogenetic testing before treatment with radioimmunotherapy may identify existing chromosomal abnormalities in previously treated patients, particularly those who have been treated with alkylating agents and purine nucleoside analogs and would be at higher risk for t-MDS or t-AML.

published online ahead of print at www.jco.org on August 20, 2007.

Presented in part in poster format at the 44th Annual Meeting of the American Society of Hematology, Philadelphia, PA, December 6-10, 2002; and abstract format at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

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

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