Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia

Hagop M. Kantarjian, Moshe Talpaz, Jorge Cortes, Susan O'Brien, Stefan Faderl, Deborah Thomas, Francis Giles, Mary Beth Rios, Jianqin Shan, Ralph Arlinghaus

Research output: Contribution to journalArticle

Abstract

Purpose: The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. Experimental Design: One hundred eighty patients with Philadelphia chromosome (Ph)-positive chronic-phase CML after IFN-α failure, treated with imatinib mesylate, had 543 simultaneous cytogenetic and QC-PCR analyses at different times during their therapy. Results: The median QC-PCR values [ratio-percentage of (BCR-ABL/ABL transcripts) × 100] for cytogenetic response categories were: no response (Ph, >90%), 36%; minor response (Ph, 35-90%), 22%; partial response (Ph, 1-34%), 7.3%; complete response (Ph, 0%), 0.89%. There was good correlation between cytogenetic and QC-PCR studies (P < 0.001; r = 0.92) and good concordance between QC-PCR values (>10%, 2-10%, and <2%) and cytogenetic response categories (none, minor, partial, complete) with a concordance rate of 66%, and major discordance of only 10%. Of 170 samples in complete cytogenetic response, 21% still had QC-PCR values of >10%, and 53% had QC-PCR values of <1%. There was excellent concordance between blood and marrow QC-PCR values (r = 0.965; P < 0.01; concordance rate, 88%; major discordance, 0%). No patient in complete cytogenetic response regardless of QC-PCR value has yet relapsed. At a median follow-up time of 26 months, higher QC-PCR values within each cytogenetic category at 3, 6, and 9 months have not been associated with a higher occurrence cytogenetic relapse or disease progression. However, the significance of this may become different with longer follow-up. Conclusion: QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.

Original languageEnglish (US)
Pages (from-to)160-166
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number1 I
StatePublished - Jan 1 2003
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Cytogenetics
Polymerase Chain Reaction
Therapeutics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Imatinib Mesylate
Philadelphia Chromosome
Residual Neoplasm
Disease Progression
Research Design
Bone Marrow
Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia. / Kantarjian, Hagop M.; Talpaz, Moshe; Cortes, Jorge; O'Brien, Susan; Faderl, Stefan; Thomas, Deborah; Giles, Francis; Rios, Mary Beth; Shan, Jianqin; Arlinghaus, Ralph.

In: Clinical Cancer Research, Vol. 9, No. 1 I, 01.01.2003, p. 160-166.

Research output: Contribution to journalArticle

Kantarjian, HM, Talpaz, M, Cortes, J, O'Brien, S, Faderl, S, Thomas, D, Giles, F, Rios, MB, Shan, J & Arlinghaus, R 2003, 'Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia', Clinical Cancer Research, vol. 9, no. 1 I, pp. 160-166.
Kantarjian, Hagop M. ; Talpaz, Moshe ; Cortes, Jorge ; O'Brien, Susan ; Faderl, Stefan ; Thomas, Deborah ; Giles, Francis ; Rios, Mary Beth ; Shan, Jianqin ; Arlinghaus, Ralph. / Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 1 I. pp. 160-166.
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abstract = "Purpose: The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. Experimental Design: One hundred eighty patients with Philadelphia chromosome (Ph)-positive chronic-phase CML after IFN-α failure, treated with imatinib mesylate, had 543 simultaneous cytogenetic and QC-PCR analyses at different times during their therapy. Results: The median QC-PCR values [ratio-percentage of (BCR-ABL/ABL transcripts) × 100] for cytogenetic response categories were: no response (Ph, >90{\%}), 36{\%}; minor response (Ph, 35-90{\%}), 22{\%}; partial response (Ph, 1-34{\%}), 7.3{\%}; complete response (Ph, 0{\%}), 0.89{\%}. There was good correlation between cytogenetic and QC-PCR studies (P < 0.001; r = 0.92) and good concordance between QC-PCR values (>10{\%}, 2-10{\%}, and <2{\%}) and cytogenetic response categories (none, minor, partial, complete) with a concordance rate of 66{\%}, and major discordance of only 10{\%}. Of 170 samples in complete cytogenetic response, 21{\%} still had QC-PCR values of >10{\%}, and 53{\%} had QC-PCR values of <1{\%}. There was excellent concordance between blood and marrow QC-PCR values (r = 0.965; P < 0.01; concordance rate, 88{\%}; major discordance, 0{\%}). No patient in complete cytogenetic response regardless of QC-PCR value has yet relapsed. At a median follow-up time of 26 months, higher QC-PCR values within each cytogenetic category at 3, 6, and 9 months have not been associated with a higher occurrence cytogenetic relapse or disease progression. However, the significance of this may become different with longer follow-up. Conclusion: QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.",
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T1 - Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia

AU - Kantarjian, Hagop M.

AU - Talpaz, Moshe

AU - Cortes, Jorge

AU - O'Brien, Susan

AU - Faderl, Stefan

AU - Thomas, Deborah

AU - Giles, Francis

AU - Rios, Mary Beth

AU - Shan, Jianqin

AU - Arlinghaus, Ralph

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N2 - Purpose: The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. Experimental Design: One hundred eighty patients with Philadelphia chromosome (Ph)-positive chronic-phase CML after IFN-α failure, treated with imatinib mesylate, had 543 simultaneous cytogenetic and QC-PCR analyses at different times during their therapy. Results: The median QC-PCR values [ratio-percentage of (BCR-ABL/ABL transcripts) × 100] for cytogenetic response categories were: no response (Ph, >90%), 36%; minor response (Ph, 35-90%), 22%; partial response (Ph, 1-34%), 7.3%; complete response (Ph, 0%), 0.89%. There was good correlation between cytogenetic and QC-PCR studies (P < 0.001; r = 0.92) and good concordance between QC-PCR values (>10%, 2-10%, and <2%) and cytogenetic response categories (none, minor, partial, complete) with a concordance rate of 66%, and major discordance of only 10%. Of 170 samples in complete cytogenetic response, 21% still had QC-PCR values of >10%, and 53% had QC-PCR values of <1%. There was excellent concordance between blood and marrow QC-PCR values (r = 0.965; P < 0.01; concordance rate, 88%; major discordance, 0%). No patient in complete cytogenetic response regardless of QC-PCR value has yet relapsed. At a median follow-up time of 26 months, higher QC-PCR values within each cytogenetic category at 3, 6, and 9 months have not been associated with a higher occurrence cytogenetic relapse or disease progression. However, the significance of this may become different with longer follow-up. Conclusion: QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.

AB - Purpose: The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. Experimental Design: One hundred eighty patients with Philadelphia chromosome (Ph)-positive chronic-phase CML after IFN-α failure, treated with imatinib mesylate, had 543 simultaneous cytogenetic and QC-PCR analyses at different times during their therapy. Results: The median QC-PCR values [ratio-percentage of (BCR-ABL/ABL transcripts) × 100] for cytogenetic response categories were: no response (Ph, >90%), 36%; minor response (Ph, 35-90%), 22%; partial response (Ph, 1-34%), 7.3%; complete response (Ph, 0%), 0.89%. There was good correlation between cytogenetic and QC-PCR studies (P < 0.001; r = 0.92) and good concordance between QC-PCR values (>10%, 2-10%, and <2%) and cytogenetic response categories (none, minor, partial, complete) with a concordance rate of 66%, and major discordance of only 10%. Of 170 samples in complete cytogenetic response, 21% still had QC-PCR values of >10%, and 53% had QC-PCR values of <1%. There was excellent concordance between blood and marrow QC-PCR values (r = 0.965; P < 0.01; concordance rate, 88%; major discordance, 0%). No patient in complete cytogenetic response regardless of QC-PCR value has yet relapsed. At a median follow-up time of 26 months, higher QC-PCR values within each cytogenetic category at 3, 6, and 9 months have not been associated with a higher occurrence cytogenetic relapse or disease progression. However, the significance of this may become different with longer follow-up. Conclusion: QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.

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