Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: Need for new response definitions?

Hagop Kantarjian, Susan O'Brien, Jianqin Shan, Xuelin Huang, Guillermo Garcia-Manero, Stefan Faderl, Farhad Ravandi-Kashani, Srdan Verstovsek, Mary Beth Rios, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy. METHODS. In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment. RESULTS. The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74% versus 62%, and of undetectable BCR-ABL transcripts 38% versus 24%. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]-positivity ≤35%) at 6 months to 12 months and survival as well as progression-free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for ≥12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71% of patients on imatinib therapy; undetectable BCR-ABL transcripts documented at least twice were noted in 34%. CONCLUSIONS. Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments.

Original languageEnglish (US)
Pages (from-to)837-845
Number of pages9
JournalCancer
Volume112
Issue number4
DOIs
StatePublished - Feb 15 2008
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Disease-Free Survival
Incidence
Survival
Leukemia, Myeloid, Chronic Phase
Therapeutics
Philadelphia Chromosome
Imatinib Mesylate

Keywords

  • Chronic myelogenous leukemia
  • Response criteria
  • Response definitions outcome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia : Need for new response definitions? / Kantarjian, Hagop; O'Brien, Susan; Shan, Jianqin; Huang, Xuelin; Garcia-Manero, Guillermo; Faderl, Stefan; Ravandi-Kashani, Farhad; Verstovsek, Srdan; Rios, Mary Beth; Cortes, Jorge.

In: Cancer, Vol. 112, No. 4, 15.02.2008, p. 837-845.

Research output: Contribution to journalArticle

Kantarjian, H, O'Brien, S, Shan, J, Huang, X, Garcia-Manero, G, Faderl, S, Ravandi-Kashani, F, Verstovsek, S, Rios, MB & Cortes, J 2008, 'Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: Need for new response definitions?', Cancer, vol. 112, no. 4, pp. 837-845. https://doi.org/10.1002/cncr.23238
Kantarjian H, O'Brien S, Shan J, Huang X, Garcia-Manero G, Faderl S et al. Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: Need for new response definitions? Cancer. 2008 Feb 15;112(4):837-845. https://doi.org/10.1002/cncr.23238
Kantarjian, Hagop ; O'Brien, Susan ; Shan, Jianqin ; Huang, Xuelin ; Garcia-Manero, Guillermo ; Faderl, Stefan ; Ravandi-Kashani, Farhad ; Verstovsek, Srdan ; Rios, Mary Beth ; Cortes, Jorge. / Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia : Need for new response definitions?. In: Cancer. 2008 ; Vol. 112, No. 4. pp. 837-845.
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abstract = "BACKGROUND. Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy. METHODS. In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment. RESULTS. The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91{\%}; however, the incidence of CGCR at 48 months into therapy was only 78{\%}. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74{\%} versus 62{\%}, and of undetectable BCR-ABL transcripts 38{\%} versus 24{\%}. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]-positivity ≤35{\%}) at 6 months to 12 months and survival as well as progression-free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for ≥12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71{\%} of patients on imatinib therapy; undetectable BCR-ABL transcripts documented at least twice were noted in 34{\%}. CONCLUSIONS. Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments.",
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T2 - Need for new response definitions?

AU - Kantarjian, Hagop

AU - O'Brien, Susan

AU - Shan, Jianqin

AU - Huang, Xuelin

AU - Garcia-Manero, Guillermo

AU - Faderl, Stefan

AU - Ravandi-Kashani, Farhad

AU - Verstovsek, Srdan

AU - Rios, Mary Beth

AU - Cortes, Jorge

PY - 2008/2/15

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N2 - BACKGROUND. Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy. METHODS. In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment. RESULTS. The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74% versus 62%, and of undetectable BCR-ABL transcripts 38% versus 24%. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]-positivity ≤35%) at 6 months to 12 months and survival as well as progression-free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for ≥12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71% of patients on imatinib therapy; undetectable BCR-ABL transcripts documented at least twice were noted in 34%. CONCLUSIONS. Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments.

AB - BACKGROUND. Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy. METHODS. In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment. RESULTS. The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74% versus 62%, and of undetectable BCR-ABL transcripts 38% versus 24%. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]-positivity ≤35%) at 6 months to 12 months and survival as well as progression-free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for ≥12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71% of patients on imatinib therapy; undetectable BCR-ABL transcripts documented at least twice were noted in 34%. CONCLUSIONS. Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments.

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KW - Response criteria

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