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Type: Journal article
Title: Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline
Author: Branford, S.
Yeung, D.
Parker, W.
Roberts, N.
Purins, L.
Braley, J.
Altamura, H.
Yeoman, A.
Georgievski, J.
Jamison, B.
Phillis, S.
Donaldson, Z.
Leong, M.
Fletcher, L.
Seymour, J.
Grigg, A.
Ross, D.
Hughes, T.
Citation: Blood, 2014; 124(4):511-518
Publisher: American Society of Hematology
Issue Date: 2014
ISSN: 0006-4971
Statement of
Susan Branford, David T. Yeung, Wendy T. Parker, Nicola D. Roberts, Leanne Purins, Jodi A. Braley, Haley K. Altamura, Alexandra L. Yeoman, Jasmina Georgievski, Bronte A. Jamison, Stuart Phillis, Zoe Donaldson, Mary Leong, Linda Fletcher, John F. Seymour, Andrew P. Grigg, David M. Ross and Timothy P. Hughes
Abstract: In chronic myeloid leukemia (CML) patients, a breakpoint cluster region-Abelson (BCR-ABL1) value >10% at 3 months of therapy is statistically associated with poorer outcome, yet many of these patients still achieve satisfactory outcomes. We investigated 528 first-line imatinib-treated patients to determine whether patients with the poorest outcome can be better discriminated at 3 months. All outcomes were significantly superior for the 410 patients with BCR-ABL1 ≤10% at 3 months (P < .001). However, the poorest outcomes among the 95 evaluable patients with BCR-ABL1 >10% at 3 months were identified by the rate of BCR-ABL1 decline from baseline, assessed by estimating the number of days over which BCR-ABL1 halved. Patients with BCR-ABL1 halving time <76 days (n = 74) had significantly superior outcomes compared with patients whose BCR-ABL1 values did not halve by 76 days (n = 21; 4-year overall survival, 95% vs 58%, P = .0002; progression-free survival, 92% vs 63%, P = .008; failure-free survival, 59% vs 6%, P < .0001; and major molecular response, 54% vs 5%, P = .008). By multivariate analysis, the halving time was an independent predictor of outcome in this poor risk group. Our study highlighted that the rate of BCR-ABL1 decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The International Randomized IFN vs STI571 (IRIS) trial was registered at as #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at as #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at as #ACTRN12607000614493. The TIDEL II trial was registered at as #ACTRN12607000325404.
Keywords: Benzamides; Piperazines; Pyrimidines; Antineoplastic Agents; Fusion Proteins, bcr-abl; Remission Induction; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Rights: © 2014 by The American Society of Hematology
RMID: 0030018380
DOI: 10.1182/blood-2014-03-566323
Appears in Collections:Medicine publications

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