期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 176, 期 4, 页码 609-617出版社
WILEY
DOI: 10.1111/bjh.14463
关键词
decitabine; methylation; fetal haemoglobin; myelodysplastic syndrome; biomarker
类别
资金
- DFG [SFB 992]
- Wilhelm-Sander-Stiftung [1999.032.2]
- EORTC Leukemia Group
- German Cancer Aid [DKH 110461]
Although azanucleoside DNA-hypomethylating agents (HMAs) are routinely used for the treatment of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), very few outcome predictors have been established. Expression of the -like globin gene locus is tightly regulated by DNA methylation, is HMA-sensitive invitro, and fetal haemoglobin (HbF) expression is under study as a potential biomarker for response of MDS patients to azacitidine. We determined HbF expression in 16 MDS and 36 AML patients receiving decitabine (DAC). Pre-treatment HbF was already elevated (>10% of total haemoglobin) in 7/16 and 12/36 patients, and HbF was induced by DAC in 81%/54% of MDS/AML patients, respectively. Elevated pre-treatment HbF was associated with longer median overall survival (OS): 266 vs. 86months for MDS (hazard ratio [HR] 856, 95% confidence interval [CI] 174-4249, P=0008, with similarly longer progression-free and AML-free survival), and 100 vs. 29months OS for AML (HR 301, 95% CI 126-722, P=0014). In a multivariate analysis, the prognostic value of HbF was retained. Time-dependent Cox models revealed that the prognostic value of treatment-induced HbF induction was inferior to that of pre-treatment HbF. In conclusion, we provide first evidence for invivo HbF induction by DAC in MDS/AML, and demonstrate prognostic value of elevated pre-treatment HbF, warranting prospective, randomized studies.
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