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, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

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 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), and 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 it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P = .005) and accelerated phase (P = .03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is 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.

Original languageEnglish (US)
Pages (from-to)3794-3800
Number of pages7
JournalBlood
Volume101
Issue number10
DOIs
StatePublished - May 15 2003
Externally publishedYes

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Clonal Evolution
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Emitter coupled logic circuits
Chromosomes
Philadelphia Chromosome
Therapeutics
Multivariate Analysis
Statistical methods
Imatinib Mesylate
Survival
Survival Analysis

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. / Cortes, Jorge E.; Talpaz, Moshe; Giles, Francis; O'Brien, Susan; Rios, Mary Beth; Shan, Jianqin; Garcia-Manero, Guillermo; Faderl, Stefan; Thomas, Deborah A.; Wierda, William; Ferrajoli, Allessandra; Jeha, Sima; Kantarjian, Hagop M.

In: Blood, Vol. 101, No. 10, 15.05.2003, p. 3794-3800.

Research output: Contribution to journalArticle

Cortes, JE, Talpaz, M, Giles, F, O'Brien, S, Rios, MB, Shan, J, Garcia-Manero, G, Faderl, S, Thomas, DA, Wierda, W, Ferrajoli, A, Jeha, S & Kantarjian, HM 2003, 'Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy', Blood, vol. 101, no. 10, pp. 3794-3800. https://doi.org/10.1182/blood-2002-09-2790
Cortes, Jorge E. ; Talpaz, Moshe ; Giles, Francis ; O'Brien, Susan ; Rios, Mary Beth ; Shan, Jianqin ; Garcia-Manero, Guillermo ; Faderl, Stefan ; Thomas, Deborah A. ; Wierda, William ; Ferrajoli, Allessandra ; Jeha, Sima ; Kantarjian, Hagop M. / Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. In: Blood. 2003 ; Vol. 101, No. 10. pp. 3794-3800.
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AU - Talpaz, Moshe

AU - Giles, Francis

AU - O'Brien, Susan

AU - Rios, Mary Beth

AU - Shan, Jianqin

AU - Garcia-Manero, Guillermo

AU - Faderl, Stefan

AU - Thomas, Deborah A.

AU - Wierda, William

AU - Ferrajoli, Allessandra

AU - Jeha, Sima

AU - Kantarjian, Hagop M.

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N2 - 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 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), and 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 it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P = .005) and accelerated phase (P = .03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is 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.

AB - 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 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), and 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 it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P = .005) and accelerated phase (P = .03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is 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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