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

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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.

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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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kantarjian, H. M., Talpaz, M., Cortes, J., O'Brien, S., Faderl, S., Thomas, D., Giles, F., Rios, M. B., 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, 9(1 I), 160-166.