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 Blood, 2 April 2009, Vol. 113, No. 14, pp. 3168-3171.
Prepublished online as a Blood First Edition Paper on December 2, 2008; DOI 10.1182/blood-2008-10-184853.

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CLINICAL TRIALS AND OBSERVATIONS

Brief report

Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens

Katherine I. Lin1,2, Constantine S. Tam1,3, Michael J. Keating1, William G. Wierda1, Susan O'Brien1, Susan Lerner1, Kevin R. Coombes4, Ellen Schlette2, Alessandra Ferrajoli1, Lynn L. Barron2, Thomas J. Kipps5, Laura Rassenti5, Stefan Faderl1, Hagop Kantarjian1, and Lynne V. Abruzzo2

1 Leukemia Department and 2 Hematopathology Department, The University of Texas M. D. Anderson Cancer Center, Houston; 3 Hematology Department, St. Vincent's Hospital, Melbourne, Australia; 4 Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston; and 5 CLL Research Consortium, University of California San Diego, Moores Cancer Center, La Jolla

Although immunoglobulin VH mutation status (IgVH MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgVH somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgVH MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgVH than those whose CLL used mutated IgVH (TTP 47% vs 82% at 6 years, P < .001). In a multivariate model considering all baseline characteristics, IgVH MS emerged as the only determinant of remission duration (hazard ratio 3.8, P < .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgVH status.


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