Elevated fetal haemoglobin is a predictor of better outcome in MDS/AML patients receiving 5-aza-2'-deoxycytidine (Decitabine)
| Autor: | Pierre W. Wijermans, Gabriele Ihorst, Rainer Claus, Stefan Suciu, Ljudmila Bogatyreva, Philipp N. Sander, Emmanuel Bissé, Michael Lübbert, Heiko Becker |
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| Rok vydání: | 2016 |
| Předmět: |
Oncology
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Antimetabolites Antineoplastic Azacitidine Decitabine Disease-Free Survival 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Internal medicine Fetal hemoglobin medicine Humans Survival analysis Fetal Hemoglobin Aged Aged 80 and over Proportional hazards model business.industry Myelodysplastic syndromes Hazard ratio Hematology DNA Methylation Middle Aged medicine.disease Prognosis Survival Analysis Leukemia Myeloid Acute 030220 oncology & carcinogenesis Myelodysplastic Syndromes Biomarker (medicine) Female business Biomarkers 030215 immunology medicine.drug |
| Zdroj: | British journal of haematology. 176(4) |
| ISSN: | 1365-2141 |
| Popis: | 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 β-like globin gene locus is tightly regulated by DNA methylation, is HMA-sensitive in vitro, 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 (>1·0% 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): 26·6 vs. 8·6 months for MDS (hazard ratio [HR] 8·56, 95% confidence interval [CI] 1·74-42·49, P = 0·008, with similarly longer progression-free and AML-free survival), and 10·0 vs. 2·9 months OS for AML (HR 3·01, 95% CI 1·26-7·22, P = 0·014). 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 in vivo HbF induction by DAC in MDS/AML, and demonstrate prognostic value of elevated pre-treatment HbF, warranting prospective, randomized studies. |
| Databáze: | OpenAIRE |
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