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Ruxolitinib is approved for polycythemia vera (PV) patients after failure to previous cytoreductive therapy, based on durable results observed in phase 3 trials. We report a multicenter retrospective study demonstrating the efficacy and safety of ruxolitinib in real-life setting. Eighty-three patients were evaluated. Median follow-up was 24.5 months (IQR 14.0-29.3). At a 3-month response assessment, ruxolitinib provided significant benefit in reducing hematocrit (HCT) level (p 0.001), phlebotomy requirement (p 0.001), leucocytes (p = 0.044), and disease-related symptoms (p 0.001). The exposure-adjusted rates (per 100 patient-years) of infectious complications, thromboembolic events, and secondary malignancies were 6.9, 3, and 3.7, respectively. Non-melanoma skin cancers (NMSC) were the most frequent (40%) SM type. Lymphoproliferative disorders were not detected. Five (6%) patients permanently discontinued ruxolitinib treatment and four (5%) evolved in myelofibrosis (MF), but none in acute leukemia. The rate of MF evolution per 100 patient-years of exposure was 2.8. In our experience, ruxolitinib confirmed its efficacy and safety outside of clinical trials.

Limited information is available on the impact of the COVID-19 pandemic on the management of chronic myeloid leukaemia (CML). The Campus CML network collected retrospective information on 8665 CML patients followed at 46 centres throughout Italy during the pandemic between February 2020 and January 2021. Within this cohort, we recorded 217 SARS-CoV-2-positive patients (2·5%). Most patients (57%) were diagnosed as having SARS-CoV-2 infection during the second peak of the pandemic (September 2020 to January 2021). The majority (35%) was aged between 50 and 65years with a male prevalence (73%). Fifty-six percent of patients presented concomitant comorbidities. The median time from CML diagnosis to SARS-CoV-2 infection was six years (three months to 18years). Twenty-one patients (9·6%) required hospitalization without the need of respiratory assistance, 18 (8·2%) were hospitalized for respiratory assistance, 8 (3·6%) were admitted to an intensive care unit, while 170 (78%) were only quarantined. Twenty-three percent of patients discontinued tyrosine kinase inhibitor (TKI) therapy during the infection. Twelve patients died due to COVID-19 with a mortality rate of 5·5% in the positive cohort and of 0·13% in the whole cohort. We could also document sequelae caused by the SARS-CoV-2 infection and an impact of the pandemic on the overall management of CML patients.

A limited amount of data has been published in chronic-phase chronic myeloid leukemia (CP-CML) patients aged75 years treated frontline with second-generation tyrosine kinase inhibitors.To address this issue in a clinical 'real-life' setting, we retrospectively analyzed 45 CP-CML patients (pts) followed in 20 Italian Centers and treated frontline with dasatinib (DAS).Median age was 78.4 years (range 75-89.2 years). DAS starting dose was 100 mg QD in 35 pts (77.7%), 80 mg QD in 1 pts (2.2%) and 50 mg QD in 9 pts (20.1%), respectively. The median follow-up was 42.6 months (IQR 20.4 - 63.3).Grade 3 and 4 side effects, both hematological and non-hematological, were detected in 6 (13.3%) and 12 (26.6%) pts, respectively. Pleural effusions of all grades occurred in 13 pts (28.8%) after a median period of DAS exposure of 14.7 months (IQR 3.0 - 33.1). The rates of DAS dose reduction and permanent drug discontinuation were 53.3% and 20.0%, respectively. As the best response, 42/45 patients (93.3%) achieved a complete cytogenetic response (CCyR), 35/45 (77.7%) a major molecular response (MMR) and 24/45 (53.3%) a deep molecular response (both MR 4.0 and MR 4.5). Only 1 patient (2.2%) progressed to the blast phase after 13 months of therapy; 8 deaths were observed (1 CML-related and 7 CML-unrelated). Cumulative event-free survival and overall survival at 36 months were 64.7% (95%, CI 49.4 - 80.0) and 82.3% (95%, CI 70.3-94.3), respectively.These findings, although evaluated in a limited and selected cohort of patients, suggest that DAS might be effective in older patients (aged75 years) affected by CP-CML with acceptable toxicity.

Few data are available on the treatment with DFX in patients with transfusion dependent Ph- Myeloproliferative Neoplasms in fibrotic phase. Here we report 48MPNpatients and iron overload treated with DFX. Starting DFX dose was 20 mg/Kg in 23 patients, 15 mg/Kg in 20 patientsand 10 mg/Kg in 5 patients. After a median treatment of 27.6 months, 5 patients achieved ferritin500 ng/ml, 11 1000 ng/ml and 3 a reduction50% of basal ferritin with a global response rate of 41%. As to hematological improvement, 9/47 patients (19.1%) showed a persistent rise of Hb1.5 g/dl, with disappearance of transfusion requirement in 6 cases. The median OS from DFX initiation in patients with chelation response was 61.0 months compared to 15.8 months in patients without chelation efficacy. Treatment with DFX is feasible and effective in MPN with iron overload and a hematological improvement can occur in a sizeable rate of patients.

Introduction Treatment of chronic phase (CP) chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) proved to be almost equally effective in young and elderly patients. Three TKIs, imatinib (IM), dasatinib (DAS) and nilotinib (NIL), are approved for frontline therapy in Italy. Choice of frontline TKI is based on a combined evaluation of patient's characteristics and expectations, with age usually playing a prominent role. However, to date, few data are available on patterns of TKI selection in very elderly patients. Aim To analyse the use of frontline TKI therapy in a large and unselected cohort of very elderly CP-CML patients Methods We retrospectively evaluated 332 patients aged ≥75 year diagnosed from 1/2012 to 12/2019 at 36 Hematology Centres participating at the "Campus CML" project. Results Clinical features at diagnosis for the whole cohort and according to frontline TKI are reported in Table 1. As to frontline TKI, 285 patients (85.8%) received IM and 47 (14.2%) a 2G-TKI (DAS n=28, 59.5%; NIL n=19, 40.5%). Of the 285 IM-treated patients, 192 (67.3%) started with standard dose (400 mg/day) and 93 (32.7%) with a reduced dose (300 mg/day n=64, 22.5%; Following widespread introduction of generic IM in Italy in early 2018, patients were divided in 2 groups: among 238 patients diagnosed from 2012 to 2017, 198 (83.1%) received IM and 40 (16.9%) a 2G-TKI, while patients diagnosed in 2018-2019 were treated with IM in 87/94 (92.5%) cases and with a 2G-TKI in 7 (7.5%) cases only (p=0.028). Conclusions IM remains the frontline drug of choice in very elderly CML patients, and this trend seems to increase after the introduction of the generic formulation. However, 2G-TKI are used in a small but sizeable group of patients, without a clear correlation with baseline CML features, thus probably reflecting a physician's evaluation of patient's fitness and/or expectation. Efficacy and safety of initial reduced TKIs doses in the setting of very elderly patients warrant further analyses. Figure 1 Figure 1. Disclosures Latagliata: Novartis: Honoraria; BMS Cellgene: Honoraria; Pfizer: Honoraria. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Elena: CELGENE: Other: funding for meeting participation; PFIZER: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Iurlo: Novartis: Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; InCyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Abruzzese: Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Breccia: Bristol Myers Squibb/Celgene: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria; Novartis: Honoraria.

Background Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML). However, the first months of therapy are crucial, as optimal response is defined as the achievement of molecular milestones at 3, 6 and 12 months (mo.) and as many toxicities, also causing a TKI switch, are more frequent in the 1st year. Methods To evaluate achievement of early molecular response (MR) and incidence of events leading to a TKI change during the 1st year of therapy, we retrospectively studied 1650 CP-CML patients diagnosed from 2012 and 2019 at 31 Hematology Centres and treated with frontline imatinib (IM) or second-generation (2G) TKIs dasatinib or nilotinib. Optimal MR at 3, 6 and 12 mo. were assessed according to 2020 ELN recommendations. Results Frontline TKI was IM in 926 (56.1%) and 2G-TKIs in 724 (43.9%) cases: the main clinical features at diagnosis of the entire cohort and according to frontline treatment is reported in the Table 1. Commonest comorbidities were arterial hypertension (38.7%), previous neoplasm (13.6%), diabetes (11.3%), peripheral vascular diseases (7.8%), COPD (7.5%) and ischemic heart disease (6.8%). IM-treated patients were older (p Optimal MR was achieved at 3 mo. by 1186/1430 (82.9%), at 6 mo. by 1025/1352 (75.8%) and at 12 mo. by 826/1264 patients (65.3%), respectively. Total number of patients discontinuing TKI in the 1st year was 321/1650 (19.4%), being higher with IM (237/926, 25.5%) than 2G-TKIs (84/724, 11.6%) (p0.001), hematologic toxicity (1.7%, 2.0% IM vs 1.4% 2G-TKIs, p=0.25) and progression (1.0%, 1.2% IM vs 0.8% 2G-TKIs, p=0.56). Cumulative incidence of discontinuation at 3, 6 and 12 mo. were 5.6%, 10.7% and 19.3%, respectively; values for IM and 2G-TKIs at the three timepoints were 8.1%, 15.0%, 25.5% and 2.5%, 5.3%, 11.5% (p Conclusions This real-world study on over 1600 CML patients shows that almost 20% discontinue frontline TKI during the 1st year, mostly for primary resistance or toxicity. Discontinuation rates are higher with IM compared to 2G-TKIs, mostly at 3 mo. and are probably due to a lower attainment of early MR. The impact of older age, higher risks and heavier burden of comorbidities in IM patients should be considered and need deeper investigation. Figure 1 Figure 1. Disclosures Elena: GILEAD: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; CELGENE: Other: funding for meeting participation. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: InCyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Iurlo: Pfizer: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Novartis: Honoraria. Latagliata: Novartis: Honoraria; Pfizer: Honoraria; BMS Cellgene: Honoraria.

Introduction : therapy of chronic phase (CP) chronic myeloid leukemia (CML) is based on tyrosine kinase inhibitors (TKIs) in virtually all patients. Three TKIs are approved for first-line therapy in Italy: imatinib and two second-generation (2G) TKIs, dasatinib and nilotinib. Choice of the front-line TKI is based on a combined evaluation of patient's and disease characteristics, age, risk, comorbidities and concomitant medications. Treating physician's preference and, in some cases, economic considerations, particularly after the advent of generic imatinib, may play a role in TKI selection. However, to date, few data are available on TKI use in a whole nation and on the possible drivers of treatment choice. Aim of the present work was to analyse the use of front-line TKI therapy in a large, unselected cohort of Italian CP-CML patients, correlating patient's features to drug choice. Methods: in the framework of the national Campus CML program, we retrospectively evaluated 1422 patients with CP-CML diagnosed from 2012 and 2019 in 21 haematologic Centres, mostly in academic and/or tertiary hospitals, widespread through the entire Italian territory and treated frontline with imatinib, dasatinib or nilotinib. Results: median age at diagnosis was 59.9 years [interquartile range (IQR) 47.1 - 71.7], with 317 (22.3%) patients under 45 years, 552 (38.8%) between 45 and 65 years and 553 (38.9%) older than 65 years; 821 (57.7%) patients were males. Among 1364 evaluable patients, CML risk according to Sokal score was low in 540 (39.6%), intermediate in 610 (44.7%) and high in 214 (15.7%) patients respectively; the number at low, intermediate or high risk according to the novel ELTS score among 1325 evaluable patients was 759 (57.3%), 402 (30.3%) and 164 (12.4%) respectively. Considering comorbidities, 1003 (70.6%) patients had at least one active disease at the time of CML diagnosis, the most common being hypertension (n=547, 38.5%), previous neoplasms (n=185, 13.0%), diabetes (n=150, 10.6%), chronic bronchopulmonary diseases (n=114, 8.0%), acute myocardial infarction (n=95, 6.7%), previous stroke (n=36, 2.5%) and other vascular diseases (n=98, 6.9%). Among 1335 evaluable patients, 813 (60.9%) were taking at least one concomitant medication, with 280 (21.0%) taking 3-5 drugs and 140 (10.5%) taking 6+ drugs at time of TKI start. As to the frontline therapy, 794 (55.8%) received imatinib and 628 (44.2%) were treated with 2G-TKIs, (226 dasatinib and 402 nilotinib) respectively. According to age, 2G-TKIs were chosen for majority of patients aged 100,000/mm3 vs 38.2% if WBC 10 g/dl; p=0.001) and bigger spleen (65.1% if spleen >5 cm vs 44.8% if spleen 1-5 cm vs 37.3% if spleen not palpable; p5 drugs, respectively (p 45 years, intermediate or high Sokal risk, presence of some comorbidities (2nd neoplasia and stroke) and number of concomitant medications. Conclusions: preliminary results of this observational study on almost 1500 patients show that around 55% of newly diagnosed Italian CP-CML patients receive imatinib as front-line therapy, and that the use of 2G-TKI is prevalent in the younger patients and in those with no concomitant clinical conditions. The counterintuitive finding of imatinib prevalence as frontline treatment in high risk patients might be explained by the older age of these patients. Introduction of the generic formulation in 2018 seems to have fostered the use of imatinib. Figure Disclosures Breccia: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Saglio:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Ariad: Research Funding; Roche: Research Funding.

Aim of this study is to explore the role of different treatments on the development of secondary malignancies (SMs) in a large cohort of essential thrombocythemia (ET) patients. We report the experience of a regional cooperative group in a real‐life cohort of 1026 patients with ET. We divided our population into five different groups: group 0, no treatment; group 1, hydroxyurea (HU); group 2, alkylating agents (ALK); group 3, ALK + HU sequentially or in combination; and group 4, anagrelide (ANA) and/or α‐interferon (IFN) only. Patients from groups 1, 2, and 3 could also have been treated either with ANA and/or IFN in their medical history, considering these drugs not to have an additional cytotoxic potential. In all, 63 of the 1026 patients (6%) developed 64 SM during the follow‐up, after a median time of 50 months (range: 2–158) from diagnosis. In univariate analysis, a statistically significant difference was found only for gender (P = 0.035) and age (P = 0.0001). In multivariate analysis, a statistically significant difference was maintained for both gender and age (gender HR1.7 [CI 95% 1.037–2.818] P = 0.035; age HR 4.190 [CI 95% 2.308–7.607] P = 0.0001). The impact of different treatments on SMs development was not statistically significant. In our series of 1026 ET patients, diagnosed and followed during a 30‐year period, the different therapies administered, comprising HU and ALK, do not appear to have impacted on the development of SM. A similar rate of SMs was observed also in untreated patients. The only two variables which showed a statistical significance were male gender and age >60 years.

To evaluate the prognosis of patients with Essential Thrombocythemia (ET) in the first decade of the century we assessed retrospectively the thrombosis free survival (TFS) and the overall survival (OS) of the patients diagnosed from 01/01/2000 to 31/12/2009 and collected in the database of our group. The diagnosis of ET was performed with PVSG, WHO 2001 or WHO 2008 criteria, according to the period of the first observation. The whole population of 757 patients was then divided in two groups: the first (group I) with the diagnosis performed between 01/01/2000 to 31/12/2005 (334 patients) with a median follow-up of 111,9 months, the second (group II) diagnosed between 01/01/2006 to 31/12/2009 (385 patients) with a median follow-up of 58,2 months. The main clinical features of the two groups of patients are reported in the Table 1. No difference was observed between the two groups as to age, gender, platelet and WBC count, Hb level, Cardio-Vascular Risk Factors (CVRF), spleen enlargement and occurrence of previous thrombotic events. The frequency of the JAK-2 V617F mutation resulted significantly different (49.1% vs 68.4%) but in the group I the search of the mutation was never performed at the diagnosis. The TFS and OS were calculated from the date of diagnosis to the date of any appropriate event or to the date of last follow-up with Kaplan-Meier product limit method; the comparison of proportions and median values was computed with the Chi-squared and the Mann-Withney tests, as indicated. No significant difference emerged neither for TFS (p= 0,09, HR 1,42, 95% C.I. 0.89-2.30) nor for OS (p= 0,15, HR 1,34, 95% C.I. 0,87-2,06). We also considered the type of treatment used in the two groups to assess the potential link between the therapy and TFS or OS. No difference emerged between the two groups as to anti-aggregating treatment (mainly ASA), equally utilized in both groups [287/369, 77,8%, and 330/383, 78,3%, respectively (p = 0,95)]. As for the cyto-reductive therapy, Hydroxyurea was used in 74.8% vs 67.9% (p= 0.60) and alkylating agents in 1.9% vs 2.1% (p= 0.85), whereas Anagrelide was used in 10,6% vs 3,9% (p= 0,001) and Interferon in 9,5% vs 5,2% (p= 0,037), respectively. This more frequent use of Anagrelide and Interferon in the first group (2000-2005) did not modify TFS and OS of the patients. In conclusion, no improvement was observed in the prognosis of ET patients in the recent years: thus, new efforts to identify patients at risk and the introduction of new drugs as JAK-2 inhibitors are warranted to improve the prognosis of these patients. Table Table. Disclosures Breccia: Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Honoraria; Ariad: Honoraria. Cimino:Celgene: Honoraria; Bristol-Mayer: Honoraria. Lo Coco:Pfizer: Consultancy; Baxalta: Consultancy; Novartis: Consultancy; Lundbeck: Honoraria, Speakers Bureau; Teva: Consultancy, Honoraria, Speakers Bureau. Latagliata:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria.

Dasatinib (DAS) has been licensed for the frontline treatment in chronic myeloid leukemia (CML). However, very few data are available regarding its efficacy and toxicity in elderly patients with CML outside clinical trials. To address this issue, we set out a "real-life" cohort of 65 chronic phase CML patients older than 65 years (median age 75.1 years) treated frontline with DAS in 26 Italian centers from June 2012 to June 2015, focusing our attention on toxicity and efficacy data. One third of patients (20/65: 30.7%) had 3 or more comorbidities and required concomitant therapies; according to Sokal classification, 3 patients (4.6%) were low risk, 39 (60.0%) intermediate risk, and 20 (30.8%) high risk, whereas 3 (4.6%) were not classifiable. DAS starting dose was 100 mg once a day in 54 patients (83.0%), whereas 11 patients (17.0%) received less than 100 mg/day. Grade 3/4 hematologic and extrahematologic toxicities were reported in 8 (12.3%) and 12 (18.5%) patients, respectively. Overall, 10 patients (15.4%) permanently discontinued DAS because of toxicities. Pleural effusions (all WHO grades) occurred in 12 patients (18.5%) and in 5 of them occurred during the first 3 months. DAS treatment induced in 60/65 patients (92.3%) a complete cytogenetic response and in 50/65 (76.9%) also a major molecular response. These findings show that DAS might play an important role in the frontline treatment of CML patients >65 years old, proving efficacy and having a favorable safety profile also in elderly subjects with comorbidities.

INTRODUCTION: Essential Thrombocytemia (ET) is the most common of the myeloproliferative neoplasms, vascular complications contribute mostly to both morbidity and mortality. The ability to identify thrombotic risk of the individual patient is necessary for a correct therapeutic management. Traditionally, risk stratification for thrombosis in ET pts was based on the respective absence and/or presence of either age >60 years or history of thrombosis. Recently, the IPSET score (International Prognostic Score Of Thrombosis for ET) was developed to better predict the occurrence of thrombotic events in ET patients. Risk factors included in the new score were: age, cardiovascular risk factors, previous thrombosis, presence of JAK 2 V617F mutation. AIM: to evaluate the validity of IPSET-thrombosis score in a cohort of ET patients from "Gruppo Laziale for Myeloproliferative Ph negative Neoplasms" in predicting thrombosis incidence. METHODS: from January 1978 to December 2011 we observed 1249 ET patients, median follow up was 105 months (range 12.1-417.7). We were able to retrospectively evaluate all the IPSET risk factors in 680 ET patients and estimated the clinical implication of the IPSET-thrombosis score system. According to the score 27.3 %, 19.1% and 53.5% of pts were stratified in low, intermediate and high risk group respectively. RESULTS: median age at the time of diagnosis was 61.8 yrs (range 19.9 -94; 64% females), median hemoglobin was 14 g/dl (range 6-20); median leukocyte count was 8.8 x 109/L (range 1,2-57); median platelets count was 812x 109/L (range 108-3582). We observed, during a median follow-up of 200 months, 82 thrombotic events (total incidence 17,89 %). According IPSET-thrombosis risk, in our ET population was documented a statistically different thrombosis free survival (TFS) (Gray test 0.1316): 85%, 78%, 77% in low,intermediate and high risk group respectively. During all the observation period the intermediate and high risk group showed a similar probability of thrombotic events. CONCLUSIONS: in our retrospective study the IPSET score was able to differentiate the rate of thrombosis events in low-risk (0-1 risk factors) from that of intermediate (>= 2 risk factors) and high risk (>= 3 risk factors) ET pts. Unfortunately the intermediate and high risk groups show a similar incidence of thrombotic events during the whole observation period. We were not able to verify the clinical benefit resulting from the different treatment strategies. Because treatment options in ET pts are tailored according to thrombotic risk, and since we have specified therapeutic indications for patients with low and high risk, it is necessary to validate the score IPSET in a large prospective, long term study to discriminate a true "intermediate" subset of patients for which there are no currently defined therapeutic guidelines. Disclosures No relevant conflicts of interest to declare.

The protective effect of higher platelet count at diagnosis of Essential Thrombocythemia (ET) was reported in some papers (Carobbio A. 2011, Palandri F. 2012, Montanaro M., 2014). As at our knowledge, there is no study specifically addressing this point; in this retrospective analysis we have examined 1201 ET patients (pts) followed in 11 Hematological centers of our region from 1/1978 to 12/2010. The diagnosis of ET was made with PVSG, WHO 2001 and WHO 2008 criteria, respectively, according to the period of 1st observation. The main features of our cohort were as follows: median age 62,9 yrs (19-96), male/female 435/766 (36.2%/63.8%), median WBC count 8,8 x 106/L (1.2-57.7), median Hb level 14.0 g/dl (6.0-20.5), median platelet count 813 x 106/L (457-3582), JAK-2V617F mutation in 498/834 performed pts (59,7 %) with a median allele burden of 19.6% (0.2-99.9%), spleen enlargement in 226 pts (18.7%), previous thrombosis in 17.9% of pts (arterial 14.1%, venous 3.8%). The median follow-up of the entire cohort was 7.75 yrs. Thrombosis-free survival curves were plotted according to Kaplan-Meier method and independent risk factors were identified with the Cox proportional-hazards method. At the multivariate analysis, negative prognostic factors for TFS resulted: previous thrombotic events (p= 0.012), age ≥60 yrs (p= 0.008) and spleen enlargement (p= 0.039): on the contrary, platelet count ≥ 944.109/L resulted a protective factor for TFS [p= 0.031 with an HR 0,57 (C.I. 95% 0,35-0,95)]. Receiver operating characteristic (ROC) analyses based on thrombotic events during follow-up were used to identify the baseline platelet count of 944 x 109/L as the best threshold for predicting thrombotic events. Thrombotic events according to this cutoff were 40/384 (10.3%) in pts with platelet count ≥ 944 x 109/L and 109/817 (13.3%) in pts with platelet count < 944 x 109/L. The sites of thrombosis are reported in the table. A comparison of the main features in these two populations showed that pts with PLT count < 944 x 109/L were older (median age 60.4 yrs vs 57.1 yrs, p= 0.016), had a lower median WBC count (8.8 x 109/L vs 10.6 x 109/L, p< 0.0001), an higher median Hb level (14.1 g/dL vs 13.6 g/dL, p< 0.0001) and an higher rate of JAK-2V617F mutation (67.2% vs 41.6%, p< 0.0001); no differences were observed between the two groups as to thrombotic events before diagnosis, spleen enlargement and cardiovascular risk factor (p=NS). As to the treatment, both groups resulted equally treated with anti-aggregant agents (84,6% vs 87,4%, p= 0,76) while in pts with platelet count Disclosures No relevant conflicts of interest to declare.

To predict leukemic transformation (LT), we evaluated easily detectable diagnostic parameters in 338 patients with primary myelofibrosis (PMF) followed in the Latium region (Italy) between 1981 and 2010. Forty patients (11.8%) progressed to leukemia, with a resulting 10-year leukemia-free survival (LFS) rates of 72%. Hb (

A retrospective analysis on chronic lymphocytic leukemia (CLL) patients ≤55 years observed at a single institution was performed with the purpose of characterizing the clinical features and outcome of young CLL and of identifying patients with different prognostic features. Over the period from 1984 to 1994, 1,011 CLL patients (204 [20%] ≤55 years of age and 807 [80%] >55 years of age) were observed. At diagnosis, younger and older patients displayed a similar distribution of clinical features, except for a significantly higher male/female ratio in younger patients (2.85 v 1.29;P < .0001). Both groups showed an elevated rate of second primary cancers (8.3% v 10.7%), whereas the occurrence of Richter’s syndrome was significantly higher in younger patients (5.9% v 1.2%; P < .00001). Younger and older patients showed a similar overall median survival probability (10 years) but were characterized by a different distribution of causes of deaths: CLL unrelated deaths and second primary malignancies predominated in the older age group, whereas the direct effects of leukemia were prevalent in the younger age group. Although younger and older patients displayed a similar survival, the evaluation of the relative survival rates showed that the disease had a greater adverse effect on the expected survival probability of the younger population. Multivariate analysis showed that for young CLL patients only dynamic parameters, such as lymphocyte doubling time and other signs of active disease, were the independent factors that significantly influenced survival probability (P = .00001). A prolonged clinico-hematologic follow-up allowed us to identify two subsets of young CLL patients with a different prognostic outcome: a group of patients (40%) with long-lasting stable disease without treatment and an actuarial survival probability of 94% at 12 years from diagnosis and another group (60%) with progressive disease and a median survival probability of 5 years after therapy. For the latter patients, the therapeutic effect of innovative therapies with curative intents needs to be investigated in prospective, comparative clinical trials.

Background Dasatinib has been recently licensed for first line treatment of patients with chronic myeloid leukemia (CML). However, very few data are available as to toxicity and efficacy of dasatinib in unselected elderly CML patients. Aim To address this issue, we revised a “real-life” cohort of 43 CML patients in chronic phase aged > 65 years treated with frontline dasatinib in 19 Italian Centers from 6/2012 to 6/2014 focusing on toxicity and efficacy data. Methods The main clinical features of the patients at diagnosis were as follows: M/F 20/23 (46.5%/53.5%), median age 75.2 years [interquartile range (IQR) 70.3 – 79.8), median Hb 12.5 g/dl (IQR 11.0 – 13.7), median WBC 57.7 x 109/l (IQR 29.5 – 100.0), median PLTS 466 x 109/l (IQR 249 – 758). According to Sokal risk classification, 3 patients (6.9%) were low risk, 26 (60.4%) intermediate risk, 10 (23.2%) high risk while 4 (9.5%) were not classificable. 20/43 patients (46.5%) had ≥ 2 comorbidities requiring concomitant therapies: according to ECOG scale, performance status at baseline was 0 – 1 in 36 patients (83.7%) and 2 in 7 patients (16.3%). Results Median interval from diagnosis to dasatinib start was 23 days (IQR 14 – 32). Dasatinib starting dose was 140 mg/day in 1 patient (2.3%), 100 mg/day in 33 patients (76.7%) and < 100 mg/day in 9 patients (21.0%), respectively. After a median period of treatment of 9.7 months (IQR 4.3 – 17.5) all patients were evaluable for toxicity; on the whole, grade 3 – 4 hematological and extra-hematological toxicities were reported in 4 (9.3%) and 6 (13.9%) patients, respectively. Overall, 7 patients (16.2%) permanently discontinued dasatinib due to toxicity (2 patients in the first 3-month period of treatment and 5 beyond that period). Pleural effusions of all WHO grades occurred in 7 patients (16.2%): in 2 of them the pleural effusion occurred during the first 3-month period of treatment. As to treatment efficacy, 6 patients were considered too early to be evaluated (< 3 months of treatment) and 37 were evaluable for cumulative response; on the whole, 33/37 patients (89.1%) achieved complete cytogenetic response (CCyR) and 23/37 (62.1%) also a major molecular response (MMolR). Response to treatment at different time-points is shown on | | 3rd month | 6th month | 12th month | | ------------------------------------------------------ | -------------------- | --------------------- | --------------------- | | Not evaluable: Too early Not performed | 11 6 5 | 13 11 2 | 19 19 0 | | Evaluable | 32 | 30 | 24 | | Discontinuation | 2 (6.2%) | 4 (13.3%) | 6 (25%) | | Less than CCyR | 6 (18,7%) | 2 (6.7%) | | | CCyR only | 17 (53.1%) | 5 (16.6%) | 4 (16.6%) | | MMolR | 7 (21.9%) | 19 (63.3%) | 14 (58.4%) | Table. Conclusions Present data shows that dasatinib could have a major role in the treatment of unselected patients aged > 65 years; indeed, dasatinib seems very effective and has a favourable safety profile also in elderly subjects with comorbidities. Disclosures Latagliata: Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Shire: Consultancy. Gugliotta: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Breccia: novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy.

Background Deferasirox (DFX) is an oral iron chelator widely employed to reduce iron overload in patients with myelodysplastic syndromes; in this subset, an unexpected hematological improvement (HI) has been reported in about 20% of cases by several groups. At present, only few case reports showed a similar HI in patients with Ph- Myeloproliferative Neoplasms (MPN) and transfusional requirement receiving DFX treatment. Aim To address the incidence of HI during DFX treatment in MPN patients, we revised all patients with MPN and iron overload secondary to transfusional requirement enrolled in the database of our regional cooperative group who received a treatment with deferasirox. Methods Twenty-eight patients [M/F 22/6, median age at diagnosis 68.8 years, interquartile range (IQR) 63.2 – 74.3] were reported in the database. Of them, 25 had a primary Myelofibrosis, 2 a post Essential Thrombocythemia myelofibrotic phase (MP) and 1 a post Polycythemia Vera MP. An HI was considered as a rise in Hb values ≥ 1.5 g/dl and/or a reduction in the transfusional requirement ≥ 50% lasting at least 3 months. Results Treatment with DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1 – 43.1) and from transfusion requirement of 10.0 months (IR 5.7 – 15.9). Median Hb and ferritin values at baseline were 7.8 g/dl (IQR 7.2 – 8.4) and 1,415 ng/ml (IQR 1,168 – 1768), respectively. Starting DFX dose was 1,500 mg/day in 13 patients, 1,250 mg/day in 5 patients, 1,000 mg/day in 9 patients and 3 months) rise of Hb levels > 1.5 g/dl, with disappearance of transfusional requirement in 4 cases and reduction ≥ 50% in the remaining 2 cases. The main clinical features of these 6 patients at DFX initiation and at HI are reported in the Table. Table 1.GenderAge (yrs)Months from diagnosisMonths from transfusionsHb (g/dl)Ferritin (ng/ml)Hb at HI (g/dl)Ferritin at HI (ng/ml)Months to HI# 1M68.7101.545.28.21,59010.127218# 2M67.513.313.28.7130911.265912# 3M77.29.86.08.017909.6168212# 4F76.721.715.39.1121410.5104112# 5M71.86.94.66.8264110.884924# 6M67.179.46.78.070610.05006 The HI was achieved together with a reduction of ferritin levels in 4 cases, while it was independent by ferritin response in the remaining 2 cases. To identify factors predicting the achievement of HI, many features at baseline (age, gender, Hb and ferritin levels, interval from diagnosis to DFX treatment) were compared between patients obtaining or not HI: however, none of them showed a significant role. Conclusions Treatment with DFX is feasible and effective in MPN with iron overload. Moreover, it is worth of note and deserves further biological and clinical insights that also in this setting an hematological improvement can occur in a sizeable rate of patients. Disclosures Latagliata: Novartis: Consultancy; Bristol Myers-Squibb: Consultancy; Celgene: Consultancy; Shire: Consultancy. Breccia:Celgene: Consultancy; BMS: Consultancy; novartis: Consultancy.

Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by trilinear marrow expansion and an increased susceptibility to thrombo-embolic complications. Data of 623 patients (pts) followed in 11 Hematological centers of our region from 1978 to December 2010 were collected in our database. The diagnosis was made according to PVSG criteria, WHO 2001 and 2008 criteria, respectively, based on the year of diagnosis. The main epidemiological and clinical features of all pts are reported in table. Of 623 pts, 161( 25,8%) died, 87 (13,9%) were lost to follow up and 375 (73,1%) were alive at the time of evaluation. The median follow up was 8.5 years. The thrombotic events during follow-up were 107 (17,2% of 622 evaluable pts): the arterious events were 67 (10.8%), the venous were 40 (6,4 %). The rate of thrombosis (patients/year) was 1,71 %. At the univariate analysis, the risk factors for thrombosis-free survival (TFS) at diagnosis that resulted statistically significant were: age (> 60 yrs, p= 0,036), WBC (> 10.2 x 109/L, p= 0,034), previous thrombosis (p< 0,0001). The presence of cardiovascular risk factors, Hb (>18.2 g/dL), PLT count (either > 457 x 109/L or >1000 x 109/L), JAK2V617F allele burden > 59.15% and spleen enlargement, did not reach the cut-off value of significance. At multivariate analysis with the Cox proportional hazards model method, age (> 60 yrs, p= 0,049) previous thrombotic events (p< 0.0001) and platelet count < 457 x 106/L (p= 0.019) maintained an independent prognostic value (p< 0,05), while WBC count (> 10.2 x 109/L, p =0,065) did not. The risk factors significant for overall survival (OS) at univariate analysis were: age > 60 yrs (p 10.2 x 109/L (p< 0,0001), previous thrombosis (p< 0,0001). diabetes (p= 0,0008), platelet count< 457 x 109/L (p= 0.013) and spleen enlargement (p= 0.02); Hb level < 18,2 gr% showed only a trend of significance (p= 0.056), while allele burden of JAK2 > 59.15% and the presence of at least 1 CV risk factor did not reach the cut-off value of significance. At multivariate analysis, age (p< 0,0001), WBC count > 10.2 x 109/L (p< 0,0001), previous thrombosis (p= 0,0004), diabetes (p= 0.0035) and Hb level < 18,2 gr% (p= 0.0078) maintained their independent prognostic value on OS; in contrast platelet count < 457 x 109/L and spleen enlargement lost their prognostic significance. In conclusion our retrospective analysis of a large series of PV confirm the prognostic value of age and previous thrombosis on TFS and OS, while seems to exclude any impact of spleen enlargement and high Hb level. Interesting, PLT count and Hb below median value resulted as independent risk factors for TFS and OS, respectively. Table CARACTERISTICS Evaluable N. VALUE Number of patients 623 Age years: median, (range) 63 (21 - 91) Gender, F/M : number, (%) 289 (46,4) / 334 (53,6) WBC x 109/L: median, (range) 582 10,2 (3.5-37.6) Hb g/dL: median, (range) 580 18,2 (10,5-24,8) Htc ; median, range (%) 581 56 (36-78) Plt x 109/L: median, (range) 587 457 (169-1790) JAK2 V617F : mutated / performed, (%) 386 364/386 (94,3%) JAK2 V617F quantitative (%): median, (range) 252 59,15 (0,3-99,9) Splenomegaly: number, (%) 588 247/588 (42 %) Epatomegaly: number, (%) 606 167/606 (27,5%) Disclosures Breccia: novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy.

Background: MPNs including Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), are clonal hematopoietic diseases in which the discovery of molecular driver mutations (JAK2, CALR, MPL) has deeply modified diagnostic approach in recent years. To date available data on epidemiology of MPNs and perspective analysis are rare. Our aim is to study the incidence of MPN Ph negative in a specific region of Italy named Latium and its variability across five years. Moreover we prospectively report the general features of our population. Method: We present here the prospective epidemiologic analysis of 1116 adult patients affected by MPNs (PV=289, ET=550, PMF=209) diagnosed according to 2008 WHO criteria, from January 2011 to December 2015 in 15 hematological Centers (5 academic and 10 community-based Hospitals) in Latium. A total of 289 PV, 550 ET and 209PMF were identified. The overall incidence rate of 289PV was 1.0/105 in 2011 and 2012, 1.1/105 in 2013, 0.9/105 in 2014 and 2015. The overall incidence rate of 550ET was 2.0/105 in 2011, 2.4/105 in 2012, 2.2/105 in 2013, 1.8/105 in 2014 and 1,2/105 in 2015 and the overall incidence rate of 209PMF was 0.7/105 in 2011 and 2012, 1.0/105 in 2013, 0.7/105 in 2014 and 0.5/105 in 2015. We have observed also 63 cases of MPNu (36M/32F) and the incidence rate was 0.3/105 in 2011 and 2012, 0.14/105 in 2013, 0.24/105 in 2014 and 0.22/105 in 2015. Baseline features of PV, ET and PMF patients are summarized in table 1. We have also analyzed the presence of comorbidities including obesity, arhythmia and neoplasia observed at the diagnosis in 1.6, 6.2 and 4% of all population, respectively; thirty-five percent of 1116 pts presented other comorbidities such as diabetes, inflammatory bowel disease, renal and liver failure. As thrombotic risk factors we considered diabetes, dislipidemia, smoke, essential hypertension and thrombophilia observed in 11,8, 16,2, 13,2, 51,7 and 3% of total pts, respectively. Conclusions: We confirm in our prospective observational protocol the overall incidence of MPN Ph negative, previously reported in the literature and the major incidence of male gender in PV and PMF, female in of ET. The annual incidence from 2011-2015 in Latium is remained substantially the same during the observation period. The decreasing trend observed in 2015 is probably due to the different update of some Centers that was done in October 2015 not including patients diagnosed in the last two months. Disclosures Latagliata: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria. Breccia:Pfizer: Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria. Cimino:Celgene: Honoraria; Bristol-Mayer: Honoraria.

Background Deferasirox (DFX) is an oral iron chelator widely employed in the treatment of iron overload during thalassemic syndromes and myelodysplastic syndromes. Aim At present, very few data are available on the treatment with DFX in patients with Ph- Myeloproliferative Neoplasms(MPN) and transfusional requirement. Methods To address this issue, we report here on 41 patients (M 31; F 10) with MPN and iron overload secondary to transfusional requirement enrolled in the database of our regional cooperative group who received a treatment with DFX. Of them, 36 had a primary Myelofibrosis, 4 a post Essential Thrombocythemia myelofibrotic phase and 1 a post Polycythemia Vera myelofibrotic phase. Results According to IPSS classification, 8 patients (19.5%) resulted low/intermediate-1 risk, 14 (34.1%) intermediate-2 risk and 19 (46.4%) high-risk. The main features of the patients at diagnosis and at baseline of DFX treatment are reported in the Table. Treatment with DFX was started after a median interval from diagnosis of 13.3 months [interquartile range (IR) 7.3 - 41.1] and from start of transfusion dependence of 11.5 months (IR 5.8 - 20.2), with a median of 27 packed red cells units received (IR 18 - 37). The starting DFX dose was 20 mg/Kg in 16 patients (39.1%), 15 mg/Kg in 20 patients (48.8%) and 10 mg/Kg in 5 patient (12.1%). All patients were evaluable for toxicity:extra-hematological toxicity of all WHO grades was reported in 20/41 patients (48.8%) and consisted of gastro-intestinal symptoms in 7 patients, transient renal impairment in 10 patients and skin reactions in 3 patients: however, only 3 patients (7.3%) needed a permanent discontinuation for toxicity. Thirty-nine out 41 patients were evaluable for response (> 6 months of treatment). As to chelation efficacy, after a median treatment period of 15.4 months (IR 8.1 - 22.3), 4 patients achieved ferritin levels < 500 ng/ml, 10 patients ferritin levels < 1,000 ng/ml and 2 patients presented a reduction > 50% of basal ferritin but with levels > 1,000 ng/ml, with a global response rate of 16 out 39 patients (41.0%): among the remaining 23 patients, 2 discontinued for early toxicity, 20 did not have any ferritin reduction and 1 had an early unrelated death (< 6 months of treatment). As to hematological improvement, 7/39 patients (17.9%) showed an unexpected and persistent rise of Hb levels > 1.5 g/dl, with disappearance of transfusional requirement in 5 cases. The median overall survival of the whole cohort from DFX initiation was 20.7 months (95% CI 16.0 - 25.3): the median overall survival from DFX initiation in patients with chelation response was 46.9 months (95% CI 10.7 - 83.0) compared to 14.0 months (95% CI 5.6 - 22.3) in patients without chelation efficacy (p=0.002). Conclusions Treatment with DFX is feasible and effective in MPN with iron overload. Moreover, also in this setting an hematological improvement can occur in a sizeable rate of patients. Disclosures Breccia: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Latagliata:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria.

Abstract 5062 Thrombotic events occurring before or at diagnosis of Essential Thrombocythemia (ET) are a worldwide recognized prognostic factor for the incidence of thrombosis during the follow-up of ET patients: however, these previous thrombotic events have been considered on the whole in the vast majority of studies, without further characterization. Among 1063 ET patients collected in the retrospective database of the “Gruppo Laziale SMPC Ph-”, we revised 186 cases with a previous thrombosis and a known data of occurrence, to evaluate the role of the interval from previous thrombotic episode and the diagnosis of ET. In 95 patients (51. 1%) previous thrombotic event occurred < 24 months before diagnosis of ET (group A) while in 91 patients (48. 9%) thrombosis occurred ≥ 24 months before diagnosis of ET (group B). Clinical features of patients at diagnosis are shown in the Table: GROUP A GROUP B p Gender (M/F) 40/55 42/49 0.636 Median age (yrs) (Interquartile range) (IR) 64.1 (52.7–71.8) 70.9 (61.0 – 78.0) 0.001 Hb median (g/dl) (IR) 13.9 (12.5 – 14.7) 14.2 (13.0 – 15.2) 0.136 PLT median (x 109/l) (IR) 800 (669 – 1066) 778 (652 – 926) 0.453 WBC median (x 109/l) (IR) 9.2 (7.8 – 11.3) 8.6 (7.1 – 10.8) 0.121 Median interval diagnosis – CHT (mos) (IR) 0.9 (0 – 7.0) 1.7 (0.4 – 5.6) 0.194 *CV risk factors (n°/%): 0.454 0 20 (21.0) 17 (18.6) 1 42 (44.2) 44 (48.3) ≥ 2 33 (34.8) 30 (33.1) Type of previous thrombosis (n°/%): 0.873 Arterial 78 (82.1) 67 (73.6) Venous 17 (17.9) 24 (26.4) * Cardiovascular (CV) risk factors at diagnosis were considered the presence of arterial hypertension, diabetes, smoking attitude, and hypercholesterolemia. In the group A, 9 out 95 patients (9. 4%) reported thrombotic episodes (5 arterial and 4 venous) during follow-up compared to 23 out 91 patients (25. 2%) (13 arterial and 10 venous) in the group B (p=0. 004). Consequently, patients of group B had a significantly higher cumulative risk of thrombosis compared to patients of group A (p=0. 0029, CI95% 1. 5 – 6. 1, RR 3. 04). In addition, it is worth of note that there was no difference in the cumulative risk of thrombosis between the patients of group A and the 877 patients without previous thrombotic events (p=0. 303, CI95% 0. 64 – 3. 21, RR 1. 24) In conclusion, the prognostic role of a previous thrombotic event in ET patients seems to be related not to the occurrence per se of the event but mainly to the interval between the event and the diagnosis of ET. Disclosures: Tafuri: Sigma Tau Pharmaceuticals: Research Funding.

Abstract 3854 Increasing age is a well-recognised risk factor for thrombotic events in patients with Essential Thrombocythemia (ET): however, few data exist on the role of other clinical and biological features in different age groups. To address this issue, we analysed retrospectively 1090 ET patients (M/F 403/687, median age 63 years, IR 17 – 96) diagnosed at 11 Hematological Institutions in the Lazio region from 1980 to 2010 and with a median period of follow-up of 84 months (IR 1 – 371). Based on the commonly adopted age threshold, 480 patients (44 %) were < 60 years (Group A) and 610 (56 %) were ≥ 60 years (Group B). Clinical and biological features as well as cardiovascular risk factors analyzed for the impact on the thrombotic risk in the two age groups are reported in the Table.Group A < 60 yearsGroup B ≥ 60 yearsPutative risk factorsRisk ratio (95% CI)P valueRisk ratio (95% CI)P valueM/F167/3132.68 (1.03–6.94)0.0029236/3741.12 (0.17–2.59)0.73WBC median (range) x 109/l8.9 (4.29–22.35)0.387 (0.149–1,004)0.06458.9 (1.2–57.7)0.79 (0.41–1.47)0.445PLTS median (range) x 109/l837 (451–3582)0.37 (0.258–1.70)0.66802 (450–3104)0.52 (0.28–0.99)0.0052Hb median, g/dL (range)14.1 (6.0–18.4)0.86 (0.33–2.24)0.76914.0 (7.0–17.8)0.87 (0.45–1.67)0.674*JAK-2 mutational status: wild type/mutated (%)53.2/46.81.57 (0.50–4.87)0.4434.1/65.90.498 (0.17–1.48)0.209Previous thrombotic events: n° (%)· All events72 (15)2.18 (0.59–7.96)0.12149 (24.4)3.01 (1.38–6.57)0.0004· within 24 months from diagnosis48 (10)1.43 (0.19–10.4)0.7464 (10.5)0.506 (0.18–1.39)0.189· within 60 months from diagnosis60 (12.5)NA0.5191 (14.9)0.323 (0.11–0.95)0.023Cardiovascular risk factors: Y/N %○ Arterial hypertension41.7/58.31.68(0.64–4.36)0.2880.7/19.30.96 (0.36–2.57)0.935○ Diabetes10.2/89.81.11 (0.23–5.15)0.8925.0/75.01.09 (0.38–3.11)0.86○ Smoking attitude45.6/54.42.78 (1.01–7.65)0.06758.3/41.71.04 (0.35–3.09)0.94○ Hyperlipidemia31.0/69.03.11(0.917–10.592)0.03951.6/48.42.31 (0.70–7.55)0.203 In Group A, 39 patients (8.1%) had at least one thrombotic event during follow-up; there were 20 (51.3%) arterial thrombosis and 19 (48.7%) venous thrombosis. In Group B, 63 patients (10.3%) had at least one thrombotic event during follow-up; there were 38 (69.4%) arterial thromboses and 25 (39.6%) venous thromboses. In group A univariate analysis for thrombosis-free survival performed by Kaplan-Meier method, disclosed a significant impact of male gender (p=0.0029, CI 1.03–6.94, HR 2.68), > 2 cardiovascular risk factors (p=0.0002, CI 1.87 – 190, HR 18.94) and isolated hyperlipidemia (p=0.039, CI 0.917 – 10.59, HR 3.11), while previous thrombotic events had no significant impact (p=0.27). By contrast, the presence of a previous thrombotic event was the only feature with a significant impact on thrombotic risk in Group B (p=0.0004, CI 1.38 – 6.55, HR 3.01). WBC and PLTS values at different cut-off levels as well as JAK-2 mutational status did not have any impact on thrombosis in either age groups. However, in group B, we observed a trend (p=0.052, CI 0.28–0.99, HR 0.52) towards a protective effect of higher PLTS values (> 800 × 109/l). In conclusion, our data seem to reinforce the need of a different thrombotic risk assessment in distinct age groups: in particular, younger patients could benefit from early recognition and treatment of well-known cardiovascular risk factors. Disclosures: No relevant conflicts of interest to declare.

The treatment of multiple myeloma (MM), a B-cell neoplasm characterized by a clonal expansion of plasma cell in the bone marrow, remains unsuccessful in a significant proportion of patients. The majority of MM patients fail to achieve a complete response (CR) with standard therapy. Bortezomib is a new drug that has been shown to induce a complete response (CR) in 10% of pre-treated patients and continues to show benefit in relapsing/refractory myeloma treatment. We report a case of 72 year-old women with IgAl and IgGK MM who resulted refractory to two different line therapies. Patient was diagnosed with MM in March 2005 following the admission to our clinic for bone pain and weight loss. Laboratory blood tests were: total protein 9,4 gr/dl; IgAl and IgGK monoclonal spike (IgG: 917; IgA: 2990, IgM