In:
International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 9 ( 2019-05-06), p. 2226-
Abstract:
A reduction in BCR-ABL1/ABL1IS transcript levels to 〈 10% after 3 months or 〈 1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values 〉 10% at 3 months but 〈 1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS 〈 10% at 3 months but 〉 1% at 6 months (event-free survival 68.2% vs. 32.7%; p 〈 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months 〉 10% but 〈 1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS 〈 10% at 3 months but 〉 1% at 6 months (75% vs. 18.2%; p 〈 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values 〈 1% at 6 months (p 〈 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.
Type of Medium:
Online Resource
ISSN:
1422-0067
DOI:
10.3390/ijms20092226
Language:
English
Publisher:
MDPI AG
Publication Date:
2019
detail.hit.zdb_id:
2019364-6
SSG:
12
