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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

Departments of Leukemia [H. M. K., J. C., S. O., S. F., D. T., F. G., M. B. R., J. S.], Bioimmunotherapy [M. T.], and Molecular Pathology [R. A.], M. D. Anderson Cancer Center, Houston, Texas 77030

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- 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) x 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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