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Santini: Novartis: Honoraria; Otsuka: Consultancy; Celgene: Honoraria, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Finelli:Novartis: Consultancy, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Gaidano:Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Morphosys: Honoraria; Roche: Consultancy, Honoraria. Oliva:Celgene: Consultancy, Other: Royalties, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; La Jolla: Consultancy; Sanofi: Consultancy, Speakers Bureau. Cilloni:celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees.

Background.MDS may be characterized by hypocellular marrow, irrespective of their WHO classification or molecular characteristics. Their prognostic weight must still be completely evaluated. MDS with hypocellular marrow tend to be considered an aplastic anemia “overlap syndrome” or a pre-aplastic anemia stage. There are no strong specific therapy recommendations, and large studies analyzing the outcome of hypocellular MDS are lacking. While selective sensitivity to immunosuppressive therapy is suggested, evidence in this sense is controversial.

Angelucci: Novartis oncology, celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Finelli:Celgene: Research Funding; Celgene: Other: Speaker fees; Novartis: Other: Speaker fees. Oliva:Celgene: Consultancy, Honoraria, Speakers Bureau. Santini:Janssen: Consultancy, Honoraria; Onconova: Other: advisory board; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Other: advisory board; Astex: Other: advisory board; Novartis: Consultancy, Honoraria.

No relevant conflicts of interest to declare.

BACKGROUND: Iron overload from chronic transfusion therapy can be extremely toxic and most patients (pts) do not receive adequate iron chelation therapy (ICT) despite evidence of transfusional iron overload (IOL). Deferasirox (DFX) is the principal option currently available for ICT in the management of IOL due to transfusion dependent anemia, such as in MDS pts. The most common adverse events (AEs) are gastrointestinal disorders, skin rash, elevations in liver enzymes levels and non-progressive transient increases in serum creatinine also in MDS pts, most of whom are elderly with significant comorbidities and side effects of other concomitant therapies. In order to achieve effective ICT with minimal toxicity in individual pts, regular monitoring to assess IOL and adverse effects of DFX treatment is essential.

No relevant conflicts of interest to declare.

Introduction:Myelodysplastic syndromes (MDS) are a highly heterogeneous group of clonal disorders, with very different prognosis in given individuals, overall survival (OS) ranging from more than 10 years (y) for the more indolent conditions to only few months (m) for the forms approaching AML; beside of the well-established disease-related prognostic systems (classical IPSS or its revised form [IPSS-R], the prognostic implication of comorbidities is emerging as a relevant patient-related factor influencing clinical outcome. Aim of our study was to evaluate the clinical impact of comorbidities in a series of MDS patients whatever treated in a “real-life” setting.

Erythropoiesis stimulating agents (ESAs) have been demonstrated to reduce the transfusion requirements in International Prognostic Scoring System (IPSS) low/Int-1 risk MDS patients and response to ESAs is associated with an improved quality of life. Response to ESAs varies from 20 to 60% according to the different studies and an association between ESAs response and a better overall survival (OS), without any disease evolution to AML has been reported. Aim of our study is to analyze the real life use of ESAs in Italy and to assess which group of lower risk MDS patients can benefit more by this treatment.From 1999 to 30 Jun 2013, 2487 patients affected by MDS were included in the Network of the Italian MDS Registries. Morphological MDS diagnosis was confirmed. Among them, 1411 IPSS low/int-1 patients with follow-up data available were selected. Furthermore we excluded the following cases: 87 patients who were treated at any time by azacytidine (n=61) or lenalidomide (n=26), 95 patients with WHO 2002 diagnosis of CMML and aCML, 96 patients with incomplete data, 84 patients unhomogeneously treated with ESAs other than EPO alpha. We obtained a final data base of 1049 cases. OS and leukemic evolution (LE) according to EPO treatment were analyzed using the Kaplan-Meier product-limit survival curve estimates and log-rank tests.Median age was 74 years, 59% of the patients were male and 41 % female. WHO 2002 classification was as follows: 296 (28 %) Refractory Anemia, 347 (33 %) refractory cytopenia with multilineage dysplasia, 94 (9%) refractory anemia with ringed sideroblasts, 46 (4 %) Del 5q, 188 (18 %) refractory anemia with excess of blasts and 78 (7 %) MDS unclassifiable. Median hemoglobin level at baseline was 10.0 g/dL. One hundred and twenty patients (11%) were previously transfused with a Hb baseline level less than 8.0 g/dL; 448 not yet transfused patients (43%) presented a mild anaemia with Hb ranging from 8 to 10 g/dL and 481 patients (46%) had a Hb level higher than 10 g/dL. Patients classification according to IPSS was as follows: low 55% (n=575); int-1 45% (n=474). 335 (32%) out of 1049 patients received EPO alpha treatment while the remaining 714 patients (68%) were supported without any ESAs treatment.The rate of erythroid response to EPO therapy was 61%. Median duration of response was 82 weeks. The response rate to EPO was significantly higher in non transfused than in transfused patients: 69% versus 14% respectively (p value < 0.001).Only 52 out of 1049 patients showed a LE and a higher incidence of LE in EPO treated patients was not observed.Considering the whole group of patients, the OS of EPO treated patients was not statistically different from untreated ones. However EPO responders patients showed a better OS in comparison to both the non responders and non-EPO treated patients (p value < 0.05).When we stratified patients according to the basal hemoglobin level (lower than 8 g/dL, from 8 to 10 g/dL and higher than 10 g/dL) in patients with Hb ranging from 8 to 10 g/dL we observed a significant improvement in OS following successful EPO treatment (median survival: EPO vs. non-EPO 64 vs. 43 months respectively; p<0.001). The response to EPO favorably affected the OS of patients with Hb level 8-10 g/dL in comparison to either non treated or non-responding patients. At the opposite the OS improvement by EPO therapy was minimum and it did not reach statistical significancy in either transfusion dependent patients with basal Hb < 8 g/dL and in patients with Hb > 10 g/dL. Even if adverse events were not prospectively recorded in the Registry, no frequent thromboembolic events was reported in EPO group in comparison to non treated patients.Our survey can suffer from selection bias due to the limits typical of a voluntary-based registry, but it can be considered a good real life picture of EPO alpha therapy in lower risk Italian MDS patients. Our data confirm that EPOa treatment is globally safe and that patients who can benefit more are the mild anemic untransfused subjects, with baseline Hb level ranging from 8 to 10 g/dL.Santini: Celgene: Honoraria; Novartis: Honoraria; GSK: Honoraria; Janssen: Honoraria.

Erythropoiesis stimulating agents (ESAs) have been demonstrated to reduce the transfusion requirements in International Prognostic Scoring System (IPSS) low/Int-1 risk MDS patients and response to ESAs is associated with an improved quality of life. Response to ESAs varies from 20 to 60% according to the different studies and an association between ESAs response and a better overall survival (OS), without any disease evolution to AML has been reported. Aim of our study is to analyze the real life use of ESAs in Italy and to assess which group of lower risk MDS patients can benefit more by this treatment.

Prognostic assessment has a crucial role in clinical evaluation of patients (pts) affected by myelodysplastic syndrome (MDS). Recently a Revised International Prognostic Scoring System (IPSS-R) has been developed (Greenberg et al, 2012) to improve the standard IPSS (Greenberg et al, 1997): it identifies five different prognostic categories mainly based on stratification of cytogenetic risk. Another prognostic score proposed in clinical practice is WPSS, based on transfusion dependency and WHO morphologic classification (Malcovati et al, 2005) subsequently modified (rWPSS) introducing level of hemoglobin in lieu of the previous not well defined variable of transfusion dependency (Malcovati et al, 2011).Aim of our study was to evaluate in a cohort of MDS pts enrolled in the Multiregional Italian MDS Registry the prognostic value of IPSS-R respect to IPSS and compare it with both WPSS and rWPSS.Among the 1918 MDS pts enrolled in the Multiregional Italian MDS Registry from 1999 to 2012 we excluded all the cases already included in the IWG-PM database that generated the IPSS-R. We thus obtained a cohort of 646 pts with complete follow up. We evaluated the prognostic power of IPSS-R respect to IPSS, WPSS and rWPSS respectively by Harrell's C statistics, analyzing as endpoints overall survival (OS), leukemic evolution (LE) and progression free survival (PFS). For LE we considered leukemic evolution as an event, while all the other causes of death were competing events. For PFS we consider either leukemic evolution or death for any causes as an event.Median age of MDS patients was 75 years (interquartile range: 69–80 years). 378 (59%) out of 646 pts were males. WHO classification was as follows: 33% RCMD, 10% RAEB-1, 9% RAEB-2, 6% CMML, 2% MDS-U, the remaining 40% were RARS, RA, isolated 5q deletion. Median follow up of censored pts was 17 months.According to IPSS score, 47% of pts were low risk, 39% Int-1, 10% Int-2 and 4% high risk. WPSS stratification was as follows: 31% were very low (VL) risk, 37% low (L), 19% intermediate (I), 11% high (H) and 2% very high (VH). By applying rWPSS stratification we obtained 30% VL, 35% L, 17% I, 15% H and 3% VH risk pts. IPSS-R risk stratification was as follows: 20% VL, 46% L, 20% I, 9% H and 5% VH risk pts.OS was analyzed according to the different scores by Kaplan-Meyer method. All prognostic systems allowed the identification of survival curves with significant differences among the different categories of risk stratification. IPSS-R application defined OS curves which better defined patients prognostic categories as shown in fig 1. In fact Harrel's C statistics demonstrated a better predictive value of the IPSS-R respect to IPSS, but also respect to WPSS and rWPSS (C=0,73; 0,63; 0,65; 0,64 respectively).Similar results have been obtained also considering time to LE (fig 2). Harrel's C statistics for LE was 0,84; 0,76; 0,78; 0,77 respectively in IPSS-R, IPSS, WPSS, rWPSS risk stratification groups.Moreover, we analyzed PFS outcomes (fig 3). Also in this case, IPSS-R showed the greatest prognostic power: Harrel's C statistics was 0,76; 0,67; 0,66; 0,69 respectively in IPSS-R, IPSS, WPSS, rWPSS risk stratification groups.In our hands, IPSS-R score demonstrated a better prognostic power respect to previously published prognostic systems (IPSS, WPSS, rWPSS). The cohort of MDS patients we employed to validate the new prognostic scoring system has a short follow up (17 months), due to the exclusion of cases already used to establish the IPSS-R system, and the majority of these are lower risk ones. We can conclude that a careful classification based on cytogenetic examination improve the prognostic power of the score. Thus, IPSS-R is confirmed to be a refined tool, easily applicable in real life and empowered respect to the currently used scores to define MDS patient prognosis.Saglio: Bristol-Myers Squibb: Consultancy, Speakers Bureau.

Abstract 1702