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Type: Journal article
Title: BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria
Author: Branford, S.
Seymour, J.
Grigg, A.
Arthur, C.
Rudzki, Z.
Lynch, K.
Hughes, T.
Citation: Clinical Cancer Research, 2007; 13(23):7080-7085
Publisher: Amer Assoc Cancer Research
Issue Date: 2007
ISSN: 1078-0432
Statement of
Susan Branford, John F. Seymour, Andrew Grigg, Chris Arthur, Zbigniew Rudzki, Kevin Lynch and Timothy Hughes
Abstract: Purpose: In the first years of imatinib treatment, BCR-ABL remained detectable in all but a small minority of patients with chronic myeloid leukemia. We determined whether BCR-ABL continues to decline with longer imatinib exposure and the incidence and consequence of undetectable BCR-ABL. Experimental Design: BCR-ABL levels were measured in a subset of 53 imatinib-treated IRIS trial patients for up to 7 years (29 first-line, 24 second-line). Levels were deemed undetectable using strict PCR sensitivity criteria. Results: By 18 months, the majority achieved a 3-log reduction [major molecular response (MMR)]. BCR-ABL continued to decline but at a slower rate (median time to 4-log reduction and undetectable BCR-ABL of 45 and 66 months for first-line). The probability of undetectable BCR-ABL increased considerably from 36 to 81 months of first-line imatinib {7% [95% confidence interval (95% CI), 0-17%] versus 52% (95% CI, 32-72%)}. Undetectable BCR-ABL was achieved in 18 of 53 patients and none of these 18 lost MMR after a median follow-up of 33 months. Conversely, MMR was lost in 6 of 22 (27%) patients with sustained detectable BCR-ABL and was associated with BCR-ABL mutations in 3 of 6. Loss of MMR was recently defined as suboptimal imatinib response. There was no difference in the probability of achieving molecular responses between first- and second-line patients but first-line had a significantly higher probability of maintaining MMR [P = 0.03; 96% (95% CI, 88-100%) versus 71% (95% CI, 48-93%)]. Conclusions: With prolonged therapy, BCR-ABL continued to decline in most patients and undetectable BCR-ABL was no longer a rare event. Loss of MMR was only observed in patients with sustained detectable BCR-ABL.
Keywords: chronic myeloid leukemia; imatinib; BCR-ABL; major molecular response; real-time quantitative PCR
Rights: © 2007 American Association for Cancer Research.
RMID: 0020073838
DOI: 10.1158/1078-0432.CCR-07-0844
Appears in Collections:Medicine publications

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