ALBERT

Description: Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.

Description: Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.

Description: Background: Life expectancy in Essential Thrombocythemia (ET) patients is superimposed to normal population. The main causes of death are thrombotic events and evolution into myelofibrotic phase or secondary myelodisplasia/acute leukemia. Approximately 50% to 65% of patients with ET carry activating mutations in the Janus kinase 2 gene (JAK2), and an additional 5% in the thrombopoietin receptor gene (MPL) whereas 10 to 20% of patients have mutated calreticulin gene (CALR). Non-mutated JAK2, CALR and MPL ET (triple negative-TN) are about 10%. Patients and methods : In this study we analysed the prognostic value of JAK2V617F, CALR and MPL mutational status on outcome and thrombotic risk in a retrospective cohort of 138 ET patients defined according to WHO criteria, diagnosed from 1974 to 2013 in a single Italian centre (Turin). JAK2V617F mutation was assessed by Quantitative Real–Time PCR on DNA from peripheral blood or bone marrow samples. JAK2 negative cases were then analyzed for CALR mutations by Gene Scan Analysis in combination with direct sequencing or MPL W515L/K by Allelic Discrimination Real-Time PCR assay. Overall survival (OS), cumulative incidence of myelofibrotic transformations (CI-MT) and thrombosis (CI-TB) were calculated from the date of diagnosis. The between-group comparison for OS was performed with the log-rank test, whereas for CI-MT and CI-TB we using the Gray’s test considering death as competing event and adjusting for presence of cardiovascular risk factors . Results: Among 138 ET patients, 103 (74.6%) carried the JAK2V617F mutation, 3 (2.2%) carried activating mutations of MPL exon 10, 16 (11.6%) carried mutations of CALR exon 9, and only 16 patients (11.6%) had none of these markers (TN). An high incidence of elevated haemoglobin levels and/or haematocrit (males 〉16.5 g/dl or 49% and females 〉16.0 g/dl or 48%) was significantly associated with JAK2 positivity [13 pts JAK2+ (14.77%) vs 0 pts JAK2- (Fisher test p=0.019)]. Similarly, the CI-TB, analysed with a competing-risk approach, was higher in patients with a JAK2 mutation [(5-year CI-TB: 23.7% JAK2, 0% CALR, 0% MPL, 12.5% TN; P

Description: Background In adults, ITP displays variable clinical presentation and different response to immune suppressive agents. The pathophysiological differences underlying these different behaviours are mostly unknown and a better knowledge of this biological heterogeneity might help identifying more targeted and rationale treatments for this disease. Purpose To identify immunogenetic features distinguishing ITP patients from controls and different subsets of ITP patients based on clinical presentation and treatment responsiveness. Several biological analyses were based on the model of autoimmune lymphoprolipherative syndrome (ALPS), a pediatric disease due to genetic defects decreasing function of the Fas death receptor that displays polyclonal lymphoproliferation, expansion of TCRαβ+ T cells double negative for CD4 and CD8 (DN T cells) and autoimmune manifestations frequently including thrombocytopenia. ALPS is mostly due to deleterious mutations of the Fas gene, but the +1239A〉C single nucleotide polymorphism (SNP) of the osteopontin gene (OPN) and several variations of the perforin gene (PRF1) can act as disease modifier. Finally, in the peripheral blood (PB) of ALPS, regulatory T cells (Treg), marginal zone B cells (MZB) and switched memory B cells (SNB) are decreased, whereas type 17 T helper cells (Th17) and production of IL-10 and IL-17 are increased. Patients and Methods Adult patients with ITP and matched controls were selected for the analyses and stratified in different clinical subsets according to the disease severity and responsiveness to therapy (asymptomatic, steroid or rituximab sensitive vs. steroid or rituximab refractory). Analyses included evaluation of Fas-mediated apoptosis, proportions of DN T cells in PB, mutation of OPN and PRF1, the percentage (%) of natural killer T cells (NKT), myeloid (mDC) and plasmacytoid dendritic cells (pDC), MZB, SMB, Treg, and Th17, intracellular production of IL-10 and IL12 in cultured mDC, intracellular and secreted IL-10 and IL-17 in cultured activated PBMC; finally, patients were evaluated for TCR monoclonality and, rituximab-untreated patients, also for BCR monoclonality. Results Analysis of Fas function and DN T cell expansion was assessed in 149 ITP patients and showed that they displayed higher frequency of defective Fas function than the controls (26/149, 17% vs. 5/100, 5%; P

Description: Introduction: Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by excessive red cell production and release of pro-inflammatory cytokines resulting in increased thrombotic risk, presence of systemic symptoms and reduced overall survival (OS). Abnormal body mass index (BMI) and comorbidities, as categorized by the Charlson Comorbidity Index (CCI), were found to influence treatment success and survival in several hematological malignancies, including myelofibrosis (MF). We evaluated the impact of CCI and BMI on the outcome of PV pts on the basis of real-world data. Methods: A network called "PV-NET" started in January 2019 including clinical/laboratory data of 2016 WHO-defined PV pts diagnosed and followed in 16 European Hematology Centers. Data cut-off was June 2019. OS was calculated from PV diagnosis to last contact or death (log-rank p). Cumulative incidences of events (thromboses, hemorrhages, infections, second neoplasia, and evolution into blast phase [BP] or MF) were conducted with Fine & Gray model with death as competing risk. Therapies were treated as time-to-event variables. Results: A total of 530 PV pts were collected. Median follow-up was 5.4 yrs (0.5-34) (total observation: 3633 pt-yrs). Main characteristics at diagnosis were: median age: 62.4 yrs (18.3-89.5); males: 53.4%; median (range) leukocyte/platelet count, x109/l: 9.8 (1.1-33)/448 (143-1386); median hemoglobin (g/dl)/hematocrit (%): 18.6/56 (males); 17.6/54.4 (females). Sixty-four (12.1%) and 34 (6.4%) pts had a thrombosis prior to or at diagnosis, respectively. At least one cardiovascular risk factor (CVRF) among smoke, diabetes, and hypertension was present in 343 pts (64.7%). Age-adjusted CCI was 0 (15.9%), 1 (18.9%), 2 (23.8%), and ≥3 (41.5%). Median BMI was 24 (17.4-37.3); 3.3%, 51.2%, 35.9% and 9.6% were underweight (BMI

Description: INTRODUCTION The incidence of secondary cancer (SC) in patients with myeloproliferative neoplasms (MPN) is high and comparable to that of thrombosis. However, the identification of patient subgroups that might be at increased susceptibility of developing SC has not been systematically addressed. We report here the results of an international case-control study (MPN-K) aimed at comparing the frequency of exposure to possible causes of SC in patients with classical MPN, polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). METHODS This European Leukaemia Network (ELN) study reports MPN patients from 28 sites of 5 European countries and Israel, diagnosed in the period from 2000 to 2016. Cases were MPN patients with concomitant diagnosis of a non-myeloid SC (n=15) or its presentation during the course of the disease (n=412). Controls were MPN patients cancer-free, matched to the paired case for sex, age (±5 years), date of MPN diagnosis (±5 years), and MPN disease duration (±6 years). A multivariable conditional logistic regression model was used to estimate the effect of selected variables on total SC risk and in different types of SC. RESULTS Among 1,259 MPN patients, there were 427 cases and 832 matched controls. Cases presented melanoma (n=20; 4.7%), non-melanoma skin cancer (n=69; 16.2% - basal/squamous cell carcinoma), non-skin solid cancer (n=290; 67.9%) including breast, ovary/uterus, colorectal, upper gastrointestinal, liver/pancreas, lung, prostate/urinary, other and lymphoproliferative diseases (n=48; 11.2%) including multiple myeloma, chronic lymphocytic leukemia, low and high grade B- and T-lymphoma. At diagnosis, there were slightly more patients with PV among SC cases (n= 152; 35.6%) than controls (n=256; 30.8%), while conversely there were slightly less ET patients among cases (n=196; 45.9%) than controls (n=426; 51.2%). Cases and controls presented similar proportion of MF diagnosis (n=79 cases, 18.5% and 150 controls, 18.0%). Driver mutations (JAK2 V617, EXON-12, CALR, MPL), non-driver mutations and abnormal karyotype were equally represented in cases and controls. Other variables such as cardiovascular risk factors, exposure to cancerogens, family history of cancer and chronic inflammatory diseases were reported with similar frequency in cases and controls. After MPN diagnosis, exposure to first and other lines of treatments until the index event, with Phlebotomy (n=193; 15.3%), Hydroxyurea (n=814; 64.7%), Anagrelide (n=14; 1.1%), Interferon (n=30; 2.4%), Pipobroman (n=8; 0.6%), Busulphan (n=13; 1.0%), Ruxolitinib (n=11; 0.9%), was similar in the two groups except for aspirin that was used less frequently (p=0.043) in cases (n=320; 74.9%) compared to controls (n=664; 79.9%). In particular, the lower use of aspirin was circumscribed to non-skin solid tumors. A multivariable analysis was carried out in all patients and stratified by different type of tumors (Table). In non-skin solid cancers, the time to exposure of the MPN disease 〉 5 years (OR=2.95; 95% CI 1.54-5.66, p=0.001) and the PV phenotype (OR=2.40, 95% CI 1.15-5.01, p=0.020) were more burdened by the incidence of events than the reference ET group. No difference in SC risk was found for MF patients compared to patients with ET. Interestingly, the independent protective role of aspirin retained its statistical significance only in non-skin SC. In non-melanoma skin cancer, multivariable analysis revealed that the presence of JAK2 mutation was less associated with SC (OR=0.32, 95% CI 0.13-0.81, p=0.016) and confirmed that exposure to HU and other cytotoxic agents was associated with a significantly higher risk of SC (OR=6.00, 95% CI 1.23-29.28, p=0.027 and OR=9.80, 95% CI 1.24-77.78, p=0.031, respectively). This finding was not seen in non-skin SC and in lymphoma. CONCLUSION The considered clinical and biological features, at MPN diagnosis, were not different in cases with SC and controls. During the course of the disease, three factors significantly and independently affected the risk of SC in these MPN patients: 1) patients with PV had a 77% higher risk than those with ET, 2) patients with MPN duration of more than 5 years had a twice higher risk than those with lower duration, 3) for the first time, we documented that in non-skin solid cancers, aspirin treatment reduced SC risk of 38%. Exposure to HU and other cytoreductive drugs was confirmed as a risk factor for non-melanoma skin cancer. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Marchetti:Gilead: Consultancy; takeda: Speakers Bureau; amgen: Speakers Bureau; janssen: Speakers Bureau. Griesshammer:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.

Description: Introduction Malignancy can be heralded by unprovoked venous thromboembolism (VTE) but also by arterial thrombosis. To date it is unknown whether this association is present also in myeloproliferative neoplasms (MPN), in which arterial thrombosis is more frequent that venous thrombosis and solid tumors are reported with an increased frequency. The MPN-K nested case-control study addressed the impact of cytoreductive drugs on the risk of developing second cancer in MPN patients (Barbui T et al, Leukemia 2019); here we re-examined the study database to evaluate the frequency and type of vascular complications in MPN patients with second cancer excluding leukemia and to establish whether arterial and venous thrombosis during follow-up after diagnosis of MPN could predict the occurrence of a second cancer. Patients and methods Cases were patients with second cancer diagnosed concurrently or subsequent to the diagnosis of MPN. Controls were MPN patients without second cancer. For each case with second cancer, up to 3 cancer-free controls were matched by each center for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. Each set consisting of one case and their matched-controls had a similar observational period (from MPN diagnosis until the index date of diagnosis for the second cancer). The study included 647 cases with second cancer (carcinoma, non-melanoma-skin cancers, hematological secondary cancer and melanoma). The most frequent category was carcinoma (n=426, 65.8%). Cases were comparable with the 1,234 matched controls for demographics, type of MPN, and exposure to potential confounders such as mutational profile, abnormal karyotype and cardiovascular risk factors. The thrombotic events of interest were ischemic stroke, transient ischemic attacks, acute coronary syndromes, peripheral arterial thrombosis, deep venous thrombosis (including thrombosis of cerebral and splanchnic veins) and pulmonary embolism. Thrombosis had to be concurrent with or in the 2 years before MPN diagnosis or occurring after MPN diagnosis. The cumulative incidence of either arterial or venous thrombosis from MPN diagnosis was estimated by the Kaplan-Meier method and was compared between cases and controls using the log-rank test. A conditional logistic regression model estimated the Odds Ratio (OR) with 95% Confidence Interval (CI) of second cancer associated with the occurrence of thrombosis before/at diagnosis of MPN and during follow-up. Other covariates were patient age, cardiovascular risk factors, the JAK2V617F mutation, and treatment during follow-up. Results Approximately 20% of either MPN cases or controls had thrombosis before MPN or at diagnosis (19.8% vs. 21.1%, respectively, p=0.462). After a median observation time from diagnosis of MPN to an index date of 4.5 years (interquartile range 1.5-8.2) in cases and 3.7 years (interquartile range 1.5-7.5) in controls, cases showed a percentage of thrombosis higher than in controls (75/647, 11.6% vs. 100/1234, 8.1%, respectively, p=0.013). Approximately one-third of thrombosis preceding cancer occurred in the 12 months before the diagnosis of second cancer (22/75, 29.3%). The excess of thrombosis in cases was due to a higher frequency of arterial thrombosis (6.2% vs. 3.7%, p=0.015), whereas no significant difference was found for venous thrombosis (5.4% vs. 4.3%, p=0.277). While the cumulative incidence of venous thrombosis over time was similar among cases and controls (p=0.864), the cumulative incidence of arterial thrombosis was higher in cases with second cancer (p=0.006) (Figure 1). The excess of arterial thrombosis after MPN diagnosis was limited to cases with carcinoma (6.8% vs 3.9%, p=0.027). In a multivariable model, arterial thrombosis during the follow-up was confirmed to be an independent predictor factor for carcinoma, with an odds ratio of 1.97 (95%CI 1.14-3.41, p=0.015). Conclusions. These findings reveal an association of arterial thrombosis with subsequent second cancer (namely carcinoma) in MPN patients. A possible biological plausibility for this link may be related to an underlying common pathogenic mechanism such as an aberrant inflammatory response consistently found in MPN. This observation may have practical implications and suggests careful clinical surveillance for early diagnosis of second cancer in MPN patients with arterial thrombosis during the follow-up. Disclosures Palandri: Novartis: Consultancy, Honoraria. Iurlo:Novartis: Other: Speaker Honoraria; Incyte: Other: Speaker Honoraria; Pfizer: Other: Speaker Honoraria. Bonifacio:Incyte: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Rumi:novartis: Honoraria, Research Funding. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Lunghi:Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Benevolo:Novartis Pharmaceuticals: Consultancy. McMullin:Italopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; Daiko Sanyo: Membership on an entity's Board of Directors or advisory committees. Griesshammer:Novartis: Consultancy, Honoraria, Speakers Bureau. Vannucchi:CTI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Rambaldi:Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau.

Description: Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2–dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).

Description: Background Polycythemia vera (PV) is a myeloproliferative neoplasm. Life expectancy of PV patients is reduced compared with general population; the course of disease is mainly marked out by thrombosis, with an incidence of about 18 x 1000 person-years and accounting for 45% of all deaths, but also by evolution to myelofibrosis (pPV-MF) and to acute myeloid leukemia (AML), both occurring with an incidence of 5 x 1000 person-years and accounting for 13% of deaths. Recently, in a large study published by IWG-MRT (Tefferi et al, Leukemia 2013) authors developed a widely applicable prognostic model, outlining three different prognostic risk groups based on age (age ≥67 years, 5 points; age 57–66 years, 2 points), leukocyte count (≥15 x109/l, 1 point) and venous thrombosis (1 point) as risk factors. Patients and Methods The aim of this study was to test this prognostic score on a retrospective consecutive series of 204 World Health Organization-defined PV patients, diagnosed from 1974 to 2013 in a single centre in Turin (Italy). We evaluated overall survival (OS) from diagnosis to death by the Kaplan Meyer method and Hazard Ratios were estimated with the Cox Models. The cumulative incidence of death due to leukemic transformation or evolution in myelofibrosis was estimated by the method proposed by Gooley et al, accounting for competing events. Results Clinical characteristics at diagnosis were: median age 65 years (31% under 57 years), 104 (51%) were male, constitutional symptoms and palpable splenomegaly were observed in 42 (21%) and 36 (18%) patients, respectively. Twenty-one (10%) patients showed leucocytosis (≥15 x 109/L) whereas thrombocytosis (≥450 x 109/L) was present in 77 (38%) patients. Fifty-three patients had previous thrombotic events (40 arterious and 13 venous). As expected, approximately 94% of the patients were positive for JAK2 mutations (V617F or exon12) analysis, performed at diagnosis or during the course of disease if PV was diagnosed before 2005. At a median follow-up of 93 months we observed 27 (13%) deaths, 26 (13%) myelofibrotic transformations and 7 (3%) leukemic evolution. The incidence of post diagnosis arterial vs venous thrombosis and major haemorrhage were 15%, 11% and 9% respectively The overall survival at 10 years was 85.3% (95%CI:77.6-90.5) and the cumulative incidence of death due to leukemic transformation or evolution in myelofibrosis adjusted for competitive risk event was 9.8% (95%IC: 4.5-15.0). According to the IWG-MRT score, patients were subdivided into three groups: low-risk (0 points), intermediate-risk (1 or 2 points) and high-risk (≥3 points) patients. The prognostic model showed a good discrimination between high-risk (n= 91; 10-year survival 68.3%; vs low-risk HR 8.48; 95%CI: 1.94-37.16), intermediate-risk (n= 49; 10-year survival 94.7%; vs low-risk HR 3.23; 95%CI: 0.62-16.68) and low-risk (n= 42; 10-year survival 100%) patient groups (fig1). The C-statistic was 0.751. Of note, in our analysis age was the prognostic factor at highest impact on OS (fig2); when we consider the older age as a only prognostic factor the discrimination between risk group was similar to those defined by IWG-MRT. The C-statistic was 0.748. We did not analyse the impact of leucocytosis and venous thrombosis in younger patients (at low risk according to IWG-MRT score) due to low number of events in our cohort. Conclusion The IWG-MRT prognostic score was confirmed as a good predictor of survival and prognosis in a retrospective cohort of consecutive PV patients. Moreover older age resulted as the prognostic factor at highest impact on OS. Disclosures: No relevant conflicts of interest to declare.