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Background Erythropoiesis‐stimulating agents effectively improve the hemoglobin levels in a fraction of anemic patients with myelodysplastic syndromes (MDS). Higher doses (HD) of recombinant human erythropoietin (rhEPO) have been proposed to overcome suboptimal response rates observed in MDS patients treated with lower “standard doses” (SD) of rhEPO. However, a direct comparison between the different doses of rhEPO is lacking. Methods A cohort of 104 MDS patients treated with HD was retrospectively compared to 208 patients treated with SD in a propensity score‐matched analysis to evaluate hematological improvement‐erythroid (HI‐E) rate induced by the different doses of rhEPO. The impact of rhEPO doses on survival and progression to leukemia was also investigated. Results Overall HI‐E rate was 52.6%. No difference was observed between different rhEPO doses (P = .28) in matched cohorts; in a subgroup analysis, transfusion‐dependent patients and patients with higher IPSS‐R score obtained a higher HI‐E rate with HD, although without significant impact on overall survival (OS). Achievement of HI‐E resulted in superior OS. At univariate analysis, a higher HI‐E rate was observed in transfusion‐independent patients (P, When compared in a propensity‐score matched analysis, standard doses of rhEPO showed similar effects to those of higher doses in anemic MDS patients. Achievement of favorable response with hematologic improvement in this clinical scenario is possible by reducing drug doses and costs.

Background: the Registro Italiano Trombocitemie (RIT) was activated mainly to evaluate the diagnosis and therapy appropriateness in the thrombocythemic patients with Ph-negative myeloproliferative neoplasm (MPN) observed in the adhering centers. Objective: to evaluate how the diagnostic and therapeutic approach changed in the RIT patients diagnosed with thrombocythemic MPN in the last two decades. Methods: the RIT centers registered by a web-based system during the years 2005-2014 their thrombocythemic MPN patients, and semesterly updated their follow-up data. For patients diagnosed before 2005, the data on diagnosis and prior follow-up were retrospectively collected. The diagnostic process and the initial treatment (started into the first year after diagnosis) were comparatively analyzed in the patients diagnosed before and after 2005. Results: the RIT centers registered 2629 patients. 2388 of them, object of this analysis, were diagnosed between1995 and 2014: 1098 (46%) in the decade 1995-2004 (Group I), and 1290 (54%) in the decade 2005-2014 (Group II). The diagnostic process in the patients of Group II and Group I included bone marrow biopsy (BMB, performed into 1 year and before any cytoreduction): 85% vs 80%, p The patients of Group II, as compared with those of Group I, showed a similar gender distribution (M/F ratio 0.61 vs 0.65, p 0.452), and had at diagnosis: a higher age (median 60 vs 57 years, p 60 years in 50% vs 45% of cases, p Moreover, they had: a lower platelet (PLT) count (median 737 vs 775 x 109/L, p 10 x 109/L in 28% vs 26% cases); a similar median levels of hematocrit (HCT %, in females 41.4 vs 41.0; in males 44.7 vs 44.6) and hemoglobin (Hb g/dL, in females 13.8 vs 13.6; in males 15.0 vs 14.9). The BMB, revised according to the WHO 2008 criteria, showed a not different distribution (p 0.21) of ET (64% vs 61%), ep-PMF (16% vs 17%), PMF (3% vs 2%), PV (4% vs 4%), and U-MPN (13% vs 16%. The JAK2 V617F mutation in patients of Group II (at diagnosis) and of Group I (after diagnosis) was found in 62% and in 58% of tested cases (p 0.054), respectively. The patients at high standard thrombotic risk were 58% vs 52%, p 0.004. In the patients of Group II and Group I the distribution of the treatment started into the first year was significantly different (p The treatment CYT ± AntiPLT was started in the patients at high standard thrombotic risk with a rate of 81% vs 80%, respectively, and in the patients at low standard thrombotic risk in 37% vs 43% of cases, respectively. The initial treatment CYT±AntiPLT was related, in multivariate analysis, both in patients of Group II and Group I, with older age (>60 and 40-60 vs 1000 and 700-1000 vs Conclusion: in the studied thrombocythemic MPN patients the real-life diagnostic approach was improved after 2005 not only due to the routine use of JAK2 tests, but also due to the higher rate of BMB done (85% vs 80%). The appropriateness of the cytoreductive treatment (CYT±AntiPLT started into one year from diagnosis) remained high in patients at high standard thrombotic risk (over 80% of cases were treated). Concomitantly, the inappropriate use of the cytoreductive drugs in patients at low standard thrombotic risk appreciably decreased (from 43% to 37% of cases). Moreover, it has to be remarked that the therapeutic approach was significantly influenced not only by older age and prior thrombosis, but also by thrombocytosis (PLT count >700 x 109/L), disease-related symptoms, and inconstantly by leukocytosis and CVRFs. Table Table. Disclosures Gugliotta: SHIRE Co.: Honoraria. Gugliotta:Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Introduction: Erythropoietic stimulating agents (ESAs) have not yet received FDA nor EMA approval to treat anemia of myelodysplastic syndromes (MDS), but ESAs are in use in this clinical setting since more than 25 years. Early studies, using various but usually "standard" doses of recombinant EPO (rEPO) (30-40.000 IU weekly), showed a disappointing overall response-rate of no more than 15-25%. In recent years most studies reported a response rate of more than 50%, provided MDS patients were selected according to favorable clinical variables determined during the years ( ie low transfusion requirement, absence of blasts, endogenous EPO levels < 500). Higher response rates with respect to early studies are probably due to higher, not weight-adjusted doses of rEPO (60-80.000 UI weekly). Nevertheless, a direct comparison between the two different schedules of rEPO treatment is still lacking, and the superiority of the so called higher doses of rEPO to standards regimens is inferred only by results of meta-analysis comparing studies performed at different times with various schedules and heterogenous cohorts of MDS patients. Objectives: We aimed at clarifying whether the erythroid response rate differed in patients exposed to higher doses versus standard doses of rEPO. Methods: Within the framework of the Italian Network of regional MDS registries established by Fondazione Italiana Sindromi Mielodisplastiche (FISM) a cohort of 103 MDS patients (pts) with anemia treated with higher doses of rEPO (40.000 IU twice a week, H) for at least 3 months within 6 months from diagnosis were identified; a second cohort of 206 pts, similar for clinical parameters known to influence response to rEPO (i.e. Hb concentrations at the time of starting treatment, IPSS score, transfusion-dependency, endogenous Epo levels at diagnosis and time of treatment from diagnosis) and treated with standard doses (40.000 IU weekly, S) were compared to the first cohort. Univariate and multivariate analysis were performed as appropriate in order to identify factors influencing clinical response to treatment. Results : Characteristics of subjects were: median Hb pre-treatment 8.9 g/dL in H cohort and 9.1 g/dL in S cohort, IPSS score Intermediate-2/high in 5% of H cohort and 8% of S cohort, transfusion-dependency in 25% of H cohort and 26% of S cohort, median EPO at diagnosis 79 IU in H cohort and 69 IU in S cohort. According to IWG 2006 criteria, after 3 months of rEPO treatment the overall erythroid response-rate among all the pts in the two cohorts was 53% (163 out of 309 pts). No difference in erythroid response-rate was found between MDS pts treated with higher doses (49 (48%) responders out of 103 cases) when compared to cases treated with standard doses (114 (55%) responders out of 206 pts, p= 0.23). As expected, IPSS score, transfusion-dependency and EPO serum levels at diagnosis were statistically associated with response. In particular, at multivariate analysis, significantly lower response-rates to rEPO were associated with transfusion-dependency (yes vs no, OR= 0.59 (95%CI: 0.44-0.79, p500 vs Conclusions : Our data, although derived by a retrospective analysis, seem to indicate that standard doses of rEPO are at least as effective as higher-doses for correcting anemia in MDS patients; in this clinical scenario, a standard-doses rEPO treatment allows for a consistent reduction of costs without precluding to achieve a durable erythroid response to rEPO. Prospective, randomized studies addressing this point are necessary to definitely address this topic. Disclosures 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.