期刊
BLOOD
卷 124, 期 4, 页码 511-518出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-03-566323
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资金
- Australasian Leukaemia and Lymphoma Group
- Novartis
- Leukaemia Foundation of Australia
- AR Clarkson Foundation
- Leukaemia Foundation of Australia/Cure Cancer Australia
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% vs5%, 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 http://www.clinicaltrials.gov as #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at http://www.clinicaltrials.gov as #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000614493. The TIDEL II trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000325404.
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