SEARCH:   Advanced

Blood, 3 September 2009, Vol. 114, No. 10, pp. 2037-2043. Prepublished online as a Blood First Edition Paper on June 30, 2009; DOI 10.1182/blood-2009-01-197715. This Article Full Text (PDF) All Versions of this Article: blood-2009-01-197715v1 114/10/2037    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Jabbour, E. Articles by Cortes, J. PubMed PubMed Citation Articles by Jabbour, E. Articles by Cortes, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 5, 2009 Accepted June 14, 2009 Long-term outcome of patients with chronic myeloid leukemia treated with second generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations Elias Jabbour, Daniel Jones, Hagop M. Kantarjian, Susan O'Brien, Constantine Tam, Charles Koller, Jan A. Burger, Gautam Borthakur, William G. Wierda, and Jorge Cortes* Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: jcortes{at}mdanderson.org. Secondary imatinib resistance in CML is due in 50% of cases to up to 75 different mutations in the BCR-ABL kinase domain, necessitating switch to one of several new tyrosine kinase inhibitors (TKIs) that act differentially on mutated BCR-ABL. We assess here whether scoring mutation based on in vitro IC50 of each TKI-mutation pair can predict long-term clinical outcome. Among 169 patients with CML after imatinib failure, mutations were detected prior to TKI switch in 41 (48%) treated with dasatinib and 45 (52%) treated with nilotinib. IC50 values for each TKI-mutation pair were stratified into high (n=42), intermediate (n=25), low (T315I, n=9), or unknown sensitivity (n=10). Hematologic and cytogenetic response rates were similar for patients with or without mutations. For patients in chronic phase (CP), hematologic and cytogenetic responses correlated with mutation score; tumors with low and intermediate scores having lower response rates than those with highly sensitive mutations, and worse event-free and overall survival. These correlations with overall survival were not seen for advanced phases. Mutation scoring can predict outcome in CML-CP with imatinib failure treated with second generation TKIs and can help in therapy selection. More complex prognostic models will be required for advanced stages of disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. Muller, J. E. Cortes, D.-W. Kim, B. J. Druker, P. Erben, R. Pasquini, S. Branford, T. P. Hughes, J. P. Radich, L. Ploughman, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations Blood, December 3, 2009; 114(24): 4944 - 4953. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020