Characteristics of Long-Term Survival in Patients With Myelodysplastic Syndrome Treated With 5-Azacyditine: Results From the Hellenic 5-Azacytidine Registry.

BACKGROUND: Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible treatment goal. PATIENTS AND METHODS: We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, on the basis of their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the third quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. The study included 626 patients, 157 in the Q3 group and 63 in the P90 group. RESULTS: Categorization per the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), and World Health Organization-based prognostic scoring system (WPSS) was found to predict long-term survival, while multivariate analysis revealed that response to 5-azacytidine was the strongest predictor of long-term survival. Nevertheless, patients with hematologic improvement (HI) and stable disease (SD) were equally distributed in the groups of short- and long-term survival. CONCLUSION: SD should not be considered a poor treatment response and should not be grouped with failure, while HI offers similar prognosis to SD and thus should not be grouped with complete and partial remission. Patients with SD should continue treatment with 5-azacytidine.

Bone marrow PARP1 mRNA levels predict response to treatment with 5-azacytidine in patients with myelodysplastic syndrome.

Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that participates in the DNA repair of malignant cells, with various consequences on their survival. We have recently shown that PARP1 mRNA levels in the bone marrow of patients with myelodysplastic syndrome (MDS) are correlated to prognosis. To evaluate PARP1 as a biomarker of response to 5-azacytidine in patients with MDS, we measured PARP1 mRNA levels by a quantitative real-time PCR in diagnostic bone marrow samples of 77 patients with MDS treated with 5-azacytidine. Patients with higher PARP1 mRNA levels had a better response to 5-azacytidine per the IWG criteria (p = 0.006) and a longer median survival after 5-azacytidine initiation (p = 0.033). Multivariate analysis revealed that PARP1 mRNA level was the only factor affecting response to treatment and survival after treatment with 5-azacytidine. A next-generation sequencing for 40 genes of interest in MDS and quantification of the methylation levels of the PARP1 promoter were also carried out in a subset of samples (16 and 18 samples respectively). It is the first time that a single, easily measurable biomarker shows a clear correlation with response to treatment and survival in a patient population consisting of previously untreated patients with MDS homogeneously treated with 5-azacytidine. The fact that PARP1 is also a treatment target in several malignancies underscores the importance of our finding for the potential use of PARP1 inhibitors in MDS.

Association of eating frequency with body fatness in pre- and postmenopausal women.

OBJECTIVE: To examine associations between eating frequency (EF) and body fatness in pre- and postmenopausal women, after excluding potential low-energy reporters. RESEARCH METHODS AND PROCEDURES: In this cross-sectional study of 220 free-living women, 64 pre- and 50 postmenopausal non-low-energy-reporting women were further analyzed (age, 24 to 74 years; BMI, 18.5 to 38.6 kg/m2). Anthropometric and body composition measurements (DXA) were performed in all study participants. EF, energy, and macronutrient intake were assessed by 3-day food record. Physical activity level and energy expenditure were assessed by self-reported questionnaire. RESULTS: No association between EF and adiposity indices was detected in premenopausal women. In contrast, EF was positively correlated with percentage body fat in postmenopausal women (r = 0.30, p = 0.03). EF was positively correlated with total energy intake in both groups and with total energy expenditure in premenopausal women only (r = 0.34, p = 0.02). Multivariate analysis revealed that, in postmenopausal women, EF was a significant predictor of body fatness (standardized beta = 0.41, p = 0.01). DISCUSSION: Frequent eating was not found to be related to adiposity in premenopausal women, but it was associated with increased body fat in postmenopausal women. Possible explanations could be that the frequent eating is not associated with a physically active lifestyle in postmenopausal women or that frequent eating predisposes women after menopause to a higher energy intake by increasing food stimuli and rendering it more difficult for them to control energy balance.