This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Branford, S. Articles by Hughes, T. Search for Related Content PubMed PubMed Citation Articles by Branford, S. Articles by Hughes, T.

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

Authors' Affiliations: ¹ Institute of Medical and Veterinary Science, Adelaide, Australia; ² Peter MacCallum Cancer Centre and University of Melbourne; ³ Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia; ⁴ Royal North Shore Hospital, Sydney, Australia; and ⁵ Novartis Pharmaceuticals Australia Pty Ltd., North Ryde, New South Wales

Requests for reprints: Susan Branford, Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000, Australia. Phone: 61-8-8222-3899; Fax: 61-8-8222-3146; E-mail: susan.branford{at}imvs.sa.gov.au.

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.

This article has been cited by other articles:

				D. M. Ross, D. B. Watkins, T. P. Hughes, and S. Branford Reverse Transcription with Random Pentadecamer Primers Improves the Detection Limit of a Quantitative PCR Assay for BCR-ABL Transcripts in Chronic Myeloid Leukemia: Implications for Defining Sensitivity in Minimal Residual Disease Clin. Chem., September 1, 2008; 54(9): 1568 - 1571. [Abstract] [Full Text] [PDF]

				J. E. Cortes Imatinib Therapy for Chronic Myeloid Leukemia: Where Do We Go Now? J. Clin. Oncol., July 10, 2008; 26(20): 3308 - 3309. [Full Text] [PDF]

				D. K. Hiwase, V. Saunders, D. Hewett, A. Frede, S. Zrim, P. Dang, L. Eadie, L. B. To, J. Melo, S. Kumar, et al. Dasatinib Cellular Uptake and Efflux in Chronic Myeloid Leukemia Cells: Therapeutic Implications Clin. Cancer Res., June 15, 2008; 14(12): 3881 - 3888. [Abstract] [Full Text] [PDF]

				G. Saglio, F. Pane, and G. Martinelli State-of-the-art Monitoring for Patients with Chronic Myeloid Leukemia ASCO Educational Book, January 1, 2008; 2008(1): 313 - 317. [Abstract] [Full Text] [PDF]