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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-09-2790.
Submitted September 12, 2002
Accepted November 25, 2002
Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy
Jorge E Cortes*, Moshe Talpaz, Francis Giles, Susan O'Brien, Mary Beth Rios, Jianqin Shan, Guillermo Garcia-Manero, Stefan Faderl, Deborah A Thomas, William Wierda, Allessandra Ferrajoli, Sima Jeha, and Hagop M Kantarjian
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
* Corresponding author; email: jcortes{at}mdanderson.org.
Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph-positive CML). However, its prognostic relevance in the era of imatinib therapy is unknown. We investigated the independent prognostic relevance of CE in 498 patients with Ph-positive CML treated with imatinib for chronic or accelerated phases. One hundred and twenty-one patients had CE alone (N=70) or with other accelerated phase criteria (N=51). Patients were compared in 4 categories: chronic phase (N=295); CE only (N=70); accelerated phase without CE (N=82); accelerated phase with CE (N=51). Statistical methods used established methodologies for univariate and multivariate analyses. In chronic and accelerated phases of CML, CE was not associated with significant differences in major or complete cytogenetic response rates, but was an independent poor prognostic factor for survival by multivariate analyses in both chronic (p=0.005) and accelerated phase (p=0.03). Multivariate analyses conducted at the 3-month landmark and including the 3-month cytogenetic response identified the 3-month response rate to supercede CE in both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response) in defining patient prognosis. We conclude that while cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, it remains an independent poor prognostic factor for survival in both chronic and accelerated phases of CML. The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy.
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