期刊
EBIOMEDICINE
卷 31, 期 -, 页码 174-181出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2018.04.018
关键词
Chronic myelomonocytic leukemia; Hypomethylating agents; Somatic mutations; Prognosis
资金
- French Ministry of Health [PHRC MAD-06]
- Janssen Inc. [2008-000470-21, NCT01251627]
Somatic ulations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing. Overall response rate (ORR) was 52%, including complete response (CR) in 28 patients (17%). In multivariate analysis, ASXL 1 mutations predicted a lower ORR (Odds Ratio [OR] = 0.85, p = 0.037), whereas TET2(mut)/A5XL1(wt) genotype predicted a higher CR rate (OR = 1.18, p = 0.011) independently of clinical parameters. With a median follow-up of 36.7 months, overall survival (OS) was 23.0 months. In multivariate analysis, RUNXImut (Hazard Ratio [HR] = 2.00, p = .011), CRCmut (HR = 1.90, p = 0.03) genotypes and higher WBC (log(10) (WBC) HR = 2.30, p = .005) independently predicted worse OS while the TET2(mut)/ASXL1(wt) predicted better OS (HR = 0.60, p = 0.05). CMML-specific scores Cl SS and GUM had limited predictive power. Our results stress the need for robust biomarkers of HMA activity in CMML and for novel treatment strategies in patients with myeloproliferative features and RUNX I mutations. (C) 2018 Published by Elsevier B.V.
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