ALBERT

Description: Retrospective studies could not proof a correlation of elevated platelet counts at diagnosis with thrombotic events. However, randomized and prospective clinical studies on platelet lowering therapies justify recommendations for the normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET). Furthermore, there is increasing evidence that leukocytosis is an important risk factor for arterial thrombosis, especially in WHO classified ET. Leukocytosis is even more pronounced in prefibrotic primary myelofibrosis (PMF) compared to WHO classified ET. Patient cohorts that were diagnosed prior to the WHO classification likely consist of a mixture of ET and prefibrotic PMF. Some authors suppose interplay between white blood cells (WBC) and platelets in patients with myeloproliferative diseases. The current study considers the Austrian cohort of a European registry, which was established to document the efficacy of the platelet-lowering therapeutic anagrelide in myeloproliferative neoplasms. Out of 845 patients, only those with a confirmed diagnosis of ET according to the PVSG classification until 2001 or according to the WHO classification thereafter were included in the analysis. Median follow up of the 620 included patients is 3.1 years (range 1.21-5.73 years), corresponding to 2428 patient years. 418 patients (67%) were females and the median age at study entry was 62 years (range 51-72 years). Thirty four patients (5.5%) experienced at least one major arterial or venous event until data analysis corresponding to 1.40 events per 100 patient years. The influence of platelet and WBC counts on thrombotic risk was assessed by correlating the first major thrombotic event with the median of all blood counts recorded during the course of the disease until an event or until end of observation. The median platelet counts until the first event occurred and until end of observation (in patients without an event) were 595.8 G/l (range 495.0-743.0 G/l) and 500.0 G/l (range 410.5-619.5 G/l), respectively, and thus were substantially different (p= 0.008). The median WBC counts until the first event occurred and until end of observation (in patients without an event) were statistically not different but might indicate a trend with 9.60 G/l (range 8.70-10.95 G/l) and 8.42 G/l (range 7.05-10.70 G/l), respectively (p=0.084). By using the calculated (Youden index) cut offs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of platelets (p= 0.008) as well as WBC counts (p= 0.011) above the cut offs until the time to a major event. Interestingly, in this analysis, the influence of higher platelet counts on major thrombotic events was more pronounced than that of higher WBC counts. The frequency of major events per 100 patient years was highest when both platelet and WBC counts ranged above the calculated cut offs and was substantially different from the frequency when both, platelet and WBC counts ranged below the cut offs (3.05 vs. 1.4, p

Description: Background Ropeginterferon alfa-2b (AOP2014/P1101) is a novel long-acting pegylated IFN-alpha-2b, composed of mainly one isoform, resulting in longer half-life and exposure time. Reduced dosing frequencies, better tolerability, improved compliance and more favorable long-term treatment outcomes in patients with polycythemia vera (PV) are expected. The drug has Orphan designation by EMA and FDA and is currently in the phase III stage of development. Study design Efficacy and safety data are being collected in the follow-up extension stage of the study (collecting the data of both Phase I and Phase II portions of the study), after the maximum tolerated dose (MTD) of ropeginterferon alfa-2b, administered subcutaneously every 14 to 28 days, has been defined earlier. Patients with confirmed diagnosis of PV, age ≥18 years, both naïve and cytoreductively pre-treated were eligible. After establishing the MTD, an extended cohort of 25 additional patients has been planned to be recruited. Complete hematological response (CR) is defined by hematocrit (Hct) 50% mutant allele burden. The present analysis was focused on long-term tolerability and safety in correlation with the dose of ropeginterferon alfa-2b in PV. Results Data on treatment as by July, 24, 2015, are covered by the current analysis. Baseline characteristics of the study cohort during short-term treatment were already presented earlier (Gisslinger et al, ASH 2013). The full analysis set and efficacy set were composed of 51 and 47 patients, respectively. Currently, the median reported treatment duration is 138 weeks, 33 patients completed their follow up for two years, 19 for three years. Starting with the week 10, Hct-level, platelet- and WBC-counts could be constantly maintained within normal range in the majority of patients. In a group of patients with the mean administered dose of 300 µg, n=11) group of 8 (73%) and 3 (27%) respectively. However, no statistical significance can be observed if correlation between the dose and response status was analyzed. 30 patients are still being treated in the study. Similarly, no association between the dose and occurrence of adverse events in the study could be observed. Complete molecular response as best individual response was observed more frequently in the high dose group 4 (36%) compared to 8 (23%) in the low dose group, while partial molecular responses were equally frequent in both dose groups (in 6/55% and 20/57%, respectively). 21 patients discontinued the study, 18 being treated with AOP2014 doses corresponding to low, and 3 to the high dose arms, corresponding to the drop-out rate of 50% and 27% in the respective arms. Interestingly, all discontinuations in the high dose group occurred within the first year of treatment (at weeks 16, 18 and 32), while the drop-outs in the low dose group (6 patients, 33%) discontinued the study after completion of their first year of treatment. Conclusions Efficacy and safety profile remain in line with expectations from other (pegylated) interferons. Overall response rate of 〉80% with cumulative CRs in 45-50%, accompanied by phlebotomy independence, normalization of hematological parameters and spleen size reduction in majority of patients have been observed. Significant and sustained JAK2 allelic burden decrease, starting from week 28 of treatment, was seen. No significant difference between the two mean dose levels regarding response rates or adverse events even during long-term treatment and observation could be observed. These finding are to be further verified in a larger prospective setting. Disclosures Gisslinger: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Janssen Cilag: Honoraria, Speakers Bureau. Buxhofer-Ausch:AOP Orphan: Research Funding. Thaler:AOP Orphan: Research Funding. Schlögl:AOP Orphan: Research Funding. Gastl:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Research Funding. Ban:AOP Orphan: Research Funding. Egle:AOP Orphan: Research Funding. Melchardt:AOP Orphan: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Willenbacher:COMET Center ONCOTYROL: Research Funding; AOP Orphan: Research Funding. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Zörer:AOP Orphan: Employment. Ammann-Mwathi:AOP Orphan: Employment. Kadlecova:AOP Orphan: Consultancy. Zagrijtschuk:AOP Orphan: Employment. Klade:AOP Orphan: Employment. Greil:Pfizer: Honoraria, Research Funding; GSK: Research Funding; Boehringer-Ingelheim: Honoraria; AOP Orphan: Research Funding; Celgene: Consultancy; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Amgen: Honoraria, Research Funding; Ratiopharm: Research Funding; Sanofi Aventis: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Roche, Celgene: Honoraria, Research Funding.

Description: Background In the recent International Prognostic Score for Thrombosis in essential thrombocythemia (IPSET-thrombosis), age and history of thrombosis were confirmed as independent risk factors for future thrombosis and the study also identified independent prothrombotic role for cardiovascular (CV) risk factors and JAK2 V617F mutation (Barbui et al. Blood 2012). Methods In the current study, we re-analyzed the original IPSET-thrombosis data in 1019 patients with WHO-defined ET in whom JAK2 mutational status was available, in order to quantify the individual contributions of JAK2 mutations and CV risk factors in conventionally-assigned low and high risk ET, as well as in age- versus thrombosis-defined high risk status. Results After a median follow-up of 6.8 and 5.0 years in conventionally-assigned low- and high-risk patients, respectively, the overall annual rate of total thrombosis (108 events) in conventionally-assigned low- and high-risk patients was 1.11%-pt/y (CI 0.81-1.52) and 2.46%-pt/y (CI 1.94-3.11) respectively (p=0.001), and the difference was mainly due to a higher frequency of arterial thrombosis in high-risk patients (p

Description: Abstract 1730 Thrombosis is one of the main complications observed in patients with myeloproliferative neoplasm (MPN). The underlying mechanisms of thrombosis are not entirely clarified. The incidence of, and risk factors for, thrombosis appear to differ in distinct and accurately diagnosed sub-entities of MPN. Similar incidences have been reported for essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) diagnosed according to the WHO 2008 criteria. However, the two sub-entities differ in terms of their risk factor profiles (Carobbio et al, Blood 2011; Buxhofer-Ausch et al, Am J Haematol 2012). A gain of function in procoagulant pathways is believed to be the reason for an inherited hypercoagulable state (Anderson et al, Crit Care Clin 2011). There is strong evidence indicating that certain thrombophilic single nucleotide polymorphisms account for increased risk of thrombotic complications (Di Castelnuovo et al, Thromb Res 2000; Shimasaki et al, J Am Coll Cardiol 1998; Elbaz et al, Stroke 2000; Mollaki et al, J Thromb Haemost 2004). Data concerning the impact of an inherited risk in patients with underlying MPN are scarce (Shetty, Thromb Res 2011). We aimed to investigate the influence of three pre-selected thrombophilic single nucleotide polymorphisms (SNPs) on the risk of thrombosis in patients diagnosed with ET or prefibrotic PMF according to the WHO 2008 criteria. In 167 patients with a valid consensus diagnosis of ET (n= 105) or prefibrotic PMF (n= 62), the thrombophilic SNPs of NOS3 (Glu 298 Asp), F7 (10 nucleotide insertion-deletion) and FCGR2A (His 131 Arg) were determined by AS-PCR or sequencing. These variables and certain disease-specific and laboratory parameters were correlated with the incidence of major arterial and venous thrombosis by using Cox-regression analysis. The latter was performed in the entire population as well as separately for ET and prefibrotic PMF. The frequency of SNPs of F7, NOS3 and FCGR2A did not differ significantly in ET and prefibrotic PMF. Notably, the homo- or heterozygous insertion variant of F7 was found to be a significant (multivariate analysis) risk factor for total thrombosis and arterial thrombosis in the entire population (HR 3.06, p= 0.0082 and HR 3.94, p= 0.0007, respectively) as well as on separate analysis of those patients with ET (HR 5.94, p= 0.001 and HR 9,47, p= 0.00024, respectively). The homozygous 298 Asp NOS variant was significantly (univariate analysis) associated with total thrombosis in the entire population (HR 3.29, p= 0.0257) as well as on separate analysis of the ET cohort (HR 4.739, p= 0.0161). These significances were lost on multivariate analysis. No significant associations were established with any of the tested thrombophilic SNPs and the risk of thrombosis in the prefibrotic PMF cohort. Our data show that the risk of thrombosis in ET diagnosed according to WHO 2008 is increased many-fold by the inherited insertion polymorphism of F7. This is very interesting because, in patients without an underlying pathological condition, this polymorphism appears to protect the organism against thrombosis by reducing FVII activity (Humphries et al, Thromb Haemost 1996). Moreover, the different impact of thrombophilic SNPs in ET compared to prefibrotic PMF might provide further evidence of the presumed difference in risk profiles between these two sub-entities of MPN. These data emphasize the importance of considering the inherited as well as acquired hypercoagulable state in patients with MPN. Larger studies are needed to confirm these findings. If proven true, we would be able to more accurately define the risk of thrombosis in an individual patient and subsequently tailor treatment and anticoagulation strategies. Disclosures: No relevant conflicts of interest to declare.

Description: There is compelling evidence that white blood cell (WBC) counts impact the risk of thrombosis in patients with myeloproliferative neoplasms (MPN) (Barbui Blood 2013). Moreover, recent publications disclosed significant differences regarding certain disease characteristics and the course of disease in WHO 2008 (Tefferi Blood 2007) classified essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) (Kvasnicka Am J Hematol 2008; Barbui JCO 2011; Buxhofer-Ausch Am J Hematol 2012). Hence, patients cohorts classified prior to WHO 2008 may likely consist of a mix of patients with ET and prefibrotic PMF. We aimed to reproduce the influence of WBC counts on the thrombotic risk in patients under real-life conditions. Therefore we assessed data of 825 Austrian patients from a patient registry for anagrelide in ET that was initiated 2001 in Austria due to an official authorities demand and is now being maintained in several Central European countries. Efficacy of treatment was assessed by investigating the course of platelet counts and event free survival relating to the first minor or major thrombotic event. WBC counts from the first available time points were correlated with the first thrombotic event. The cut off for the WBC subgroup analysis was set at 8,5 G/l. Statistical analysis was performed using the open-source R statistical software package, version 3.0.2. Non-parametric two-sided 95% confidence intervals for medians were calculated. Survival probabilities were assessed by applying the Kaplan-Meier method. For the comparison of time to event between the leukocyte- specific subgroups the log-rank test was used. Median Follow up of the study cohort is 3,07 years. Platelet count at start of anagrelide was median 777 G/l (95% CI 757-803). After 12, 24 and 36 months patients presented with median platelet counts of 473, 457 and 438 G/l, respectively. Median WBC count at start of therapy was 9 G/l (95% CI 8,7-9,3) and after 12, 24 and 36 months 8,5 G/l, 9,2 G/l and 8,7G/l, respectively. Incidence of thrombotic events per 100 patient- years was 5,14 for all events and 1,65 for major events only. 102 patients experienced at least one minor or major thrombotic event (major events n=36). Median time to the first minor or major thrombotic event was 1,27 years. Probability of event free survival at 1 year is 94,4% and at 3 years 87,6%. Patients with a baseline WBC count of higher than 8,5 G/l exhibit a significantly shorter probability of event free survival than patients below the cut off (p= 0,007 for all thrombotic events; p= 0,026 for major events only). This data proof the efficacy of anagrelide in lowering platelet counts and reducing significantly the risk of thrombotic events in patients with ET. The significantly shorter event free survival of patients with a WBC count above 8,5 G/l confirms earlier studies for the first time in a real-life setting. This result emphasizes the separation of true ET from prefibrotic PMF by using the WHO 2008 classification. Moreover, further investigations are needed to assess, whether a correlation of certain platelet and leukocyte counts modifies the risk of thrombotic events in MPN. Disclosures Schloegl: AOP Orphan Pharmaceuticals AG: Research Funding.

Description: Abstract 457 Introduction- The 2008 World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (MPN) underscore the role of bone marrow (BM) morphology in distinguishing essential thrombocythemia (ET) from early, and at times prefibrotic, primary myelofibrosis (PMF) that clinically presents like ET. The value of such a distinction in predicting clinical outcome has been questioned by some investigators. Study Design- Clinician scientists and hematopathologists from seven international centers of excellence for ET convened to design a clinicopathologic database of patients locally diagnosed and treated as ET. Study eligibility criteria included availability of treatment-naïve BM specimens obtained within one year of diagnosis. All bone marrows subsequently underwent a central blinded re-review by the author of the pertinent WHO chapter (JT) who applied strict WHO guidelines to identify cases of early PMF that were spuriously diagnosed as ET. Results- Revision of the BM biopsies according to the WHO morphological criteria confirmed ET in 891 patients (81%). Diagnosis was revised to early, prefibrotic PMF in 180 patients (16%). The remaining 33 (3%) BM specimens were qualitatively inadequate for accurate classification or represented unclassified cases. i) At presentation, early PMF, as opposed to true ET, was characterized by higher leukocyte (p

Description: Background: Ropeginterferon alfa-2b (Ropeg) is a novel long-acting monopegylated IFN-alpha-2b. Due to reduced dosing frequencies, better tolerability and improved compliance, Ropeg may be a favorable treatment option for long-term therapy in patients with polycythemia vera (PV). Study design: PEGINVERA phase I/II (NCT: 2010-018768-18), a prospective, open-label, multicenter study, investigated the efficacy and safety of Ropeg for long-term treatment in 51 patients aged ≥18 years with a confirmed diagnosis of PV, regardless of prior cytoreductive therapy. Following ≥1 year of 2-weekly treatment, patients who responded well to Ropeg were permitted to switch to a 4-weekly dosing regimen. Results: Baseline characteristics of the study cohort and interim safety and efficacy data were presented previously (Gisslinger et al., Blood, 2015). Fifty-one patients were treated: Median exposure to Ropeg was approximately 5.1 years (61 months; range: 0 to 87 months). Patients were treated for a median of approximately 2 years (98.9 weeks; (Q1-Q3: 69.0 - 117.4 weeks) on the 2-weekly regimen and 4 years (207.1 weeks; Q1-Q3: 158.6 - 242.0 weeks) on the 4-weekly regimen. The best observed individual hematological response for patients in the efficacy analysis set (FAS) was a complete hematological response for 27/42 (64.3%) and a partial response for 14/42 (33.3%) patients. Patients required a median of 34 weeks (Q1-Q3: 10-96 weeks) treatment to achieve a complete hematological response, and 10 weeks (Q1-Q3: 10-20 weeks) to achieve any hematological response. Switch from 2 to 4-week dosing regimen had no apparent effect on maintenance of response. With respect to JAK-2 allele burden, the best observed individual molecular response was a complete response for 12/42 (28.6%) patients and a partial response for 19/42 (45.2%) patients. Lowest JAK-2 values relative to baseline are presented by patient in Figure 1. Patients required a median of 82 weeks (Q1-Q3: 44-115 weeks) treatment to achieve a complete molecular response and 34 weeks (Q1-Q3: 18-55 weeks) treatment to achieve any molecular response. Irrespective of dosing regimen, molecular responses tended to increase over time. Most patients reported at least one adverse reaction (AR) to treatment (409 ARs in 48/51 [94.1%]); however, the majority (296 in 44 [86.3%] patients) were mild; 102 (in 34 [66.7%] patients) were moderate and 11 (in 10 [19.6%] patients) were severe. The most frequently reported ARs (frequency 〉20%) were arthralgia, influenza-like illness and fatigue. Twelve serious treatment emergent adverse events (TEAE) reported by 8/51 patients (15.7%) were considered to be treatment related: 2 events of depression, 2 of positive anti-thyroid antibodies, and one each of acute stress disorder, increased antinuclear antibodies, arthralgia, atrial fibrillation, fatigue, influenza-like illness, pyrexia, and increased transaminases. 25 patients completed the trial. The majority of discontinuation due to TEAE (13/21 patients) occurred in the first year, when the recommended slow up-titration of Ropeg could not be applied because of the maximum-tolerated-dose design. After the first year, only 8 additional patients discontinued because of TEAE. Conclusions: The final results of this phase I/II study of Ropeg in patients with PV support the findings of the pivotal phase III clinical trial (Gisslinger et al., Blood 2015) with respect to safety and efficacy as determined by hematological, clinical and molecular parameters. In addition, these data provide evidence that treatment with Ropeginterferon alfa-2b for up to 7 years is efficacious, well-tolerated and disease-modifying at both the 2 week and 4 week maintenance treatment regimens. Disclosures Gisslinger: AOP Orphan Pharmaceuticals AG: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Shire: Consultancy, Honoraria. Kralovics:MyeloPro Diagnostics and Research GmbH: Equity Ownership. Krauth:BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Greil:MSD: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Sandoz: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zoerer:AOP Orphan Pharmaceuticals: Employment. Empson:AOP Orphan Pharmaceuticals: Employment. Grohmann-Izay:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment.

Description: Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

Description: Current treatment strategies in the classical Philadelphia- negative myeloproliferative diseases are challenged by the compelling evidence of the important role of white blood cell (WBC) counts for the risk of thrombosis (Barbui Blood 2013). Moreover, recent publications disclosed significant differences in regards of certain disease characteristics, vascular risk profiles and prognosis between WHO 2008 (Tefferi Blood 2007) classified essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) (Kvasnicka Am J Hematol 2008; Barbui JCO 2011; Buxhofer-Ausch Am J Hematol 2012). Hence, patients cohorts classified prior to WHO 2008 may likely consist of a mix of patients with ET and prefibrotic PMF. A recent analysis of the prior to WHO 2008 classified UK-PT1 cohort demonstrated, that not blood counts at diagnosis but enhanced longitudinal WBC counts measured during the course of the disease correlate with the risk of vascular complications in ET (Campbell Blood 2012). The current study aimed to correlate longitudinal blood counts with thromboembolic events in patients from our institution, all reclassified according to WHO 2008 as prefibrotic PMF. In 76 patients with a valid consensus diagnosis of prefibrotic PMF longitudinal blood counts including hemoglobin levels, WBC counts and platelet counts were collected retrospectively from the patient’s records (most patients were followed every 3-4 months). Subsequently, these parameters along with certain disease specific and laboratory parameters were correlated with the incidence of major arterial or venous thrombosis after diagnosis by applying Cox-regression analyses. While overtime-platelet counts (mean 553.14±287.04) were significantly lower than baseline platelet counts (mean 806.61±372.51), WBC counts did not change over time (baseline mean 10.60±4.11; over-time mean 10.64±9.2). By correlating 1644 longitudinal blood counts with major venous and/ or arterial thromboembolic events after diagnosis neither a significant correlation of overtime- platelet counts with total thrombosis (p= 0.347) nor with arterial thrombosis (p= 0.516) was seen. In contrast, there was a clear statistical trend for correlation of over-time WBC counts with total thrombosis (p= 0.072) and- even more pronounced- with arterial thrombosis (p= 0.057). Comparison of these data to a cohort of 111 patients with WHO 2008 diagnosed ET will be presented. In conclusion our data presume an important role of over-time WBC counts on vascular events in patients with prefibrotic PMF. Apparently our current treatment strategies are not sufficient enough to lower WBC counts over- time. Appropriate medication for lowering WBC counts has to be implemented in future treatment concepts. Studies on larger, WHO 2008 diagnosed patient cohorts are needed to confirm and extend this important findings. Disclosures: Thiele: AOP Orphan Pharmaceuticals, Incyte, Novartis, Shire, Sanofi: Consultancy; Novartis, Shire: Research Funding; AOP Orphan Pharmaceuticals, Incyte, Novartis, Shire, Sanofi: Honoraria. Gisslinger:AOP Orphan Pharmaceuticals: Advisory Board Meeting Other, Honoraria; Novartis: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria; Sanofi-Aventis: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria; Shire: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria; Celgene: Advisory Board Meeting Other, Honoraria; Janssen: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria.

Description: Diagnosis of essential thrombocythemia (ET) has been updated in the last World Health Organization (WHO) classification. We developed a prognostic model to predict survival at diagnosis, named IPSET (International Prognostic Score for ET), studying patients with WHO-defined ET. Age 60 years or older, leukocyte count ≥ 11 × 109/L, and prior thrombosis significantly affected survival, by multivariable Cox regression. On the basis of the hazard ratio, we assigned 2 points to age and 1 each to leukocyte count and thrombosis. So, the IPSET model allocated 867 patients into 3 risk categories with significantly different survival: low (sum of points = 0; median survival not reached), intermediate (sum = 1-2; median survival 24.5 years), and high (sum = 3-4, median survival 13.8 years). The IPSET model was further validated in 2 independent cohorts including 132 WHO-defined ET and 234 Polycythemia Vera Study Group–defined ET patients. The IPSET model was able to predict the occurrence of thrombosis, and not to predict post-ET myelofibrosis. In conclusion, IPSET, based on age ≥ 60 years, leukocyte count ≥ 11 × 109/L, and history of thrombosis allows prognostic assessment of WHO-defined ET and the validation process makes IPSET applicable in all patients phenotypically appearing as ET.