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Current guidelines suggest that polycythemia vera (PV) patients maintain a strict hematocrit less than 45%. However, to date, little is known about the relationship between HCT control and PV- related symptom burden. In this study, PV patient data was analyzed from the CYTO PV trial (n = 224) and the MPN-SAF study cohort (n = 645). No significant differences in symptom burden were seen at the 6 and 12 month follow-up when evaluating prospective hematocrit control in the CYTO PV cohort. Patients in the MPN-SAF cohort with a worst item score of greater than 5/10 on the Myeloproliferative Neoplasm Symptom Total Symptom Score had a significantly lower mean hematocrit (p = .0376). These findings suggest a relationship between traditional aggressive therapy for PV and increased symptom burden with prolonged therapy. Thus, symptom burden should be considered when contemplating the choice of therapy in the second-line setting for PV.

Objectives This meta-analysis was performed to determine the effects of various cholesterol-lowering treatments on the risk of stroke and its relationship with the extent of cholesterol lowering. Background Statins reduce the incidence of stroke, and it has been proposed that such effect is independent of cholesterol lowering and is explained by alternative mechanisms. Methods We performed a meta-analysis of randomized trials of cholesterol-lowering treatments in cardiovascular disease reporting on stroke, involving 266,973 patients investigated and a cumulative 946,582 person-years of exposure, and a meta-regression analysis of the extent of stroke reduction as a function of changes in total cholesterol. Results The odds ratio (OR) for the incidence of stroke in actively treated groups versus controls was 0.88 (95% confidence interval: 0.83 to 0.94, p Conclusions Among cholesterol-lowering treatments, statins are the most effective at decreasing the risk of total stroke, but their benefit is proportional to the percent reduction of total cholesterol and low-density lipoprotein cholesterol. No lipid-lowering intervention was associated with a reduction of fatal stroke.

Despite significant progress in the prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) is a major public health problem. Statins showed consistent benefits on cardiovascular events, but scant data were available about their effects on SCD. This meta-analysis aimed to assess the effect of statins on SCD. Additional analyses were carried out to evaluate lipid reduction as a possible mediator of the effect. Randomized controlled trials from January 1966 to July 2006 were retrieved by searching the MEDLINE database. Inclusion criteria were outcome focusing on the incidence of SCD, statin treatment compared with placebo or no treatment, randomized design,or=100 patients enrolled, and follow-upor=6 months. Data were independently abstracted by 2 investigators using a standardized protocol. Ten randomized controlled trials enrolling a total of 22,275 patients were included in the meta-analysis. Risks of SCD were 3% in patients receiving statins and 3.8% in control patients. Statin treatment was associated with a significant 19% risk reduction for SCD (odds ratio 0.81, 95% confidence interval 0.71 to 0.93, p=0.003). In subgroup analysis, the benefit of statins was independent from the main characteristics of the studies and changes in patient lipid levels during the study. In conclusion, our results suggest that statins decrease the risk of SCD.

The adverse prognostic impact of metabolic syndrome (METS) in unselected populations and in patients with coronary heart disease has been previously shown. The aim of the current analysis was to evaluate the impact of METS on prognosis in chronic heart failure (HF).International Diabetes Federation criteria were used for the diagnosis of METS. Adjusted Cox regression models with all-cause and HF death as outcomes were fitted in 6648 patients enrolled in GISSI-HF trial with no missing values for the variables of interest.Risk of all-cause and HF death was significantly reduced in patients with METS compared to patients without METS (HR: 0.83, 95% CI: 0.72 to 0.95, p=0.005; HR: 0.76, 95% CI: 0.59 to 0.98, p=0.031; respectively). As compared with patients with no METS and no type 2 diabetes mellitus (DM), the risk of all-cause and HF death was significantly lower in patients with METS and no DM (HR: 0.76, 95% CI: 0.62 to 0.95, p=0.015; HR: 0.65, 95% CI: 0.42 to 0.99, p=0.046; respectively), whereas it was significantly increased in patients with DM and no METS (HR: 1.34, 95% CI: 1.21 to 1.48, p0.001; HR: 1.44, 95% CI: 1.21 to 1.72, p0.001; respectively). Patients with METS and DM showed no difference for risk of total and HF death compared with patients with no METS and no DM (HR: 1.03, 95% CI: 0.87 to 1.21, p=0.762; HR: 0.99; 95% CI: 0.73 to 1.35; p=0.963; respectively).METS is associated with reduced all-cause and HF mortality in patients with HF. HF patients with DM without METS are at the highest risk of mortality, whereas METS attenuates mortality risk in HF patients with DM.

From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2V617F status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897.

Lifestyle, health and cardiovascular risk: the results of the study "RischioPrevenzione". The substantial agreement of the recommendations aimed to promote the so called "healthy lifestyle habits" dose not coincide to a rebut body of evidences on the transferability of the guidelines into daily conditions of care. The large cohort of ~12.000 patients included in a prospective-observational and experimental study conducted by a country-wide network of 860 Italian General Practitioners, provided the opportunity of testing the yield of the broad spectrum of life habits found across ages (55 years, sex, regions, on the prognosis for fatal and not fatal events). While documenting and quantifying over the relative short period of time of the study (~ 4 years) the highly significant advantage of each of the components (diet and physical exercise) of the habits, as well as their combination, the study could be the sum as specifically important for two more general reasons: a) it is the general practice based documentation of the public health importance of recommendations in an adult old population; b) the instruments developed and tested to qualify-quantify the risk profiles are specifically praticable in the busy setting of daily care.

Background In a previous metaanalysis on the approved treatments for pulmonary hypertension, we reported that all therapies caused small changes in 6-minute walk distance over a short period, with minimal effects on hemodynamics and no effect on survival. Since that last review, 10 new clinical trials with about 1,500 patients have been published, which has increased the statistical power of our observations. Methods A systematic review of all clinical trials in pulmonary arterial hypertension was done. Results The pooled effect of all treatments strategies (relative risk [95% CI], P ) now shows a significant reduction of 39% (2%-62%, P = .041) in all-cause mortality. The benefits were confined only to patients with advanced disease for 16 weeks, regardless of which class of drug is used. When considering the effects within each drug family, no class of drug produced a statistically significant reduction in all-cause mortality. The improved survival bore no relationship with the change in 6-minute walk, the primary end point in most of the trials. Conclusions The impact of vasodilators on long-term survival in pulmonary arterial hypertension remains uncertain. Future trials need to ( a ) adopt new trial designs that can better address clinical benefits, ( b ) use new end points that incorporate our best understanding of the disease rather than the ones that are easy to administer, and ( c ) include longer durations of study and other strategies to clarify if survival is affected.

This meta-analysis was performed to determine the effects of various cholesterol-lowering treatments on the risk of stroke and its relationship with the extent of cholesterol lowering.Statins reduce the incidence of stroke, and it has been proposed that such effect is independent of cholesterol lowering and is explained by alternative mechanisms.We performed a meta-analysis of randomized trials of cholesterol-lowering treatments in cardiovascular disease reporting on stroke, involving 266,973 patients investigated and a cumulative 946,582 person-years of exposure, and a meta-regression analysis of the extent of stroke reduction as a function of changes in total cholesterol.The odds ratio (OR) for the incidence of stroke in actively treated groups versus controls was 0.88 (95% confidence interval: 0.83 to 0.94, p0.001). No treatment affected fatal strokes. Whereas statins decreased the risk of total stroke significantly (OR: 0.85, 95% confidence interval: 0.78 to 0.92; p0.001), the benefit of nonstatin interventions was smaller and not statistically significant (diet OR: 0.92, fibrates OR: 0.98, other treatments OR: 0.81). We found a significant relationship between percent reduction of total (and low-density lipoprotein) cholesterol and percent reduction of total strokes (p = 0.0017), with each 1% reduction of total cholesterol predicting a 0.8% relative risk reduction of stroke. We found no significant association between stroke reduction and changes of high-density lipoprotein cholesterol levels, and inconsistent associations with reduction of triglycerides.Among cholesterol-lowering treatments, statins are the most effective at decreasing the risk of total stroke, but their benefit is proportional to the percent reduction of total cholesterol and low-density lipoprotein cholesterol. No lipid-lowering intervention was associated with a reduction of fatal stroke.

Background: In clinical trials, statins reduce the incidence of strokes. It has been proposed that such effect is independent of cholesterol lowering and best explained by alternative mechanisms. We tested whether the effects of statins on stroke is qualitatively similar to that of other cholesterol-lowering interventions, and explained by cholesterol lowering. Methods: We reviewed the literature of randomized lipid-lowering trials reporting the stroke incidence, for a total of 176,974 patients investigated and a cumulative 627,117 patients/year exposure. Strokes incidence was related to treatments tested in the trials, and a meta-regression related the extent of stroke reduction as a function of the reduction in total cholesterol. Results: The odds ratio and 95% confidence interval (95% CI) for the total incidence of stroke in the actively-treated group compared with controls were 0.86 (0.81– 0.91, p Conclusions: Among lipid-lowering interventions, statins are effective in decreasing the risk of total stroke, but their benefit appears associated with the extent of reduction of blood cholesterol, and is in line with their greater cholesterol-lowering potency compared with non-statin interventions.

The GISSI-Prevenzione trial established the efficacy of n-3 polyunsaturated fatty acids (PUFAs) for reducing mortality in patients after recent myocardial infarction. The generalisability of such results to clinical practice could vary according to other individual patient characteristics. We analysed the GISSI-Prevenzione database to assess whether other major risk factors, comorbidities, dietary habits, or medications could interact with the efficacy of n-3 PUFA treatment to reduce total mortality. We found no evidence that concomitant disease states, habits, or interventions altered the therapeutic benefit of n-3 PUFA consumption in survivors of recent myocardial infarction.

The chronic constriction injury model is widely used in studying mechanisms of neuropathic pain. In this model neuropathic pain can be influenced by sympathetic interventions. It is assumed that similar mechanisms as in animals are responsible for pain arising from nerve entrapment syndromes in humans. The aim of the present study was to investigate if in patients with nerve entrapment nociceptive afferents can be modulated by adrenergic stimulation. Methods Twenty patients with pain due to a unilateral entrapment of the median nerve and 10 controls were included in the study. Spontaneous pain, mechanical and thermal evoked pain were assessed within the innervation territory of the lesioned nerve and the corresponding contralateral segment in patients and on the right hand side in healthy volunteers. The examinations were performed at baseline, during whole body cooling (sympathetic activation) and whole body warming (sympathetic inhibition), and after norepinephrine iontophoresis. Results All patients reported spontaneous pain. Mechanical allodynia, punctate hyperalgesia and cold allodynia was not found. According to side-to-side differences in heat pain thresholds, patients were separated in patients with ( n = 10) and without ( n = 10) heat hyperalgesia. Adrenergic stimulation did not induce or enhance spontaneous or mechanical evoked pain in any patient or control subject. However in patients with pre-existing heat hyperalgesia sympathetic stimulation aggravated heat hyperalgesia significantly. Further in these patients the decrease in heat pain thresholds observed after norepinephrine iontophoresis was significantly higher compared to patients without pre-existing heat hyperalgesia. Conclusion Sympathetic–afferent interaction does not play a major role in pain generation due to nerve entrapment. Nevertheless in a subgroup of patients nociceptive afferents show sensitivity to physiological and pharmacological sympathetic stimulation. This finding is important because it emphasises that despite there is no clinical detectable effect on pain sympathetic afferent interaction can be found.

Background Various innovative pharmacologic strategies for the treatment of patients with pulmonary hypertension have been tested in recent years. Neither their comparative efficacy on surrogate end points nor the overall impact on mortality have been formally reviewed. Methods We did a systematic overview of all randomized trials on the therapeutic yield of prostacyclin and analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors in patients with pulmonary hypertension searched in EMBASE, MEDLINE, and CINAHL databases from January 1985 to December 2005. Results Sixteen trials involving 1962 patients met the inclusion criteria. Up to 80% of the patients were in functional class III/IV with a median walking distance of 330 m at baseline. Overall, experimental treatments were associated with (1) a nonsignificant reduction in all-cause mortality (relative risk 0.70, 95% CI 0.41-1.22), (2) a minor but statistically significant improvement in exercise capacity of 42.8 m (95% CI 27.8-57.8), and (3) an improved dyspnea status by at least one functional class (relative risk 1.83, 95% CI 1.26-2.66). Changes in exercise capacity were not found to be predictive of a survival benefit. Conclusions Although confirming the limited benefits in clinical end points documented by each trial, the overview fails to support a significant survival advantage and does not support the predictive power of surrogate end points.

Background The promising development of perspectives in innovative therapeutic interventions in myelofibrosis (MF) makes the establishment of large collaborative networks ready to assure reliable comparability of cases and increasingly relevant data. This will provide assurance regarding efficiency and consistency in the development of clinical and epidemiological knowledge. We report here the results of the pilot phase of ERNEST, whose acronym defines its purpose: European Registry for Myeloproliferative Neoplasms: towards a better understanding of Epidemiology, Survival and Treatment. This project promoted by the European LeukemiaNet (ELN) collaboration is coordinated by the Fondazione Mario Negri Sud (Italy) and supported by an unrestricted educational grant by Novartis. Patients and Methods In order to test the feasibility of a prospective epidemiological outcome-oriented registry across centers, expected to vary in the characteristics of their populations and care practices, a retrospective analysis was implemented based on a strictly pre-defined protocol. Patients with Primary Myelofibrosis (PMF), Post- Essential Thrombocythemia Myelofibrosis (PET-MF) and Post- Polycythemia Vera Myelofibrosis (PPV-MF) which were diagnosed in the participant centers between January 2001 and December 2012, with available follow-up information, were eligible for inclusion. Chi-square test and Mann-Whitney test were used to compare data at presentation by diagnosis for categorical and continuous variables respectively. Standard time-to-event methods were used for data analysis, including log-rank test, Kaplan-Meier survival graphs, and Cox proportional hazards models to calculate hazard ratios along with 95% confidence intervals (CI). Multivariable analysis was performed adjusting for unbalanced and relevant prognostic covariates. Results From February 2013 to May 2014, we received data of 1209 evaluable patients from 13 centers in 5 European countries (Italy, Germany, Spain, United Kingdom, Sweden): 61% were PMF, 20% PET-MF and 19% PPV-MF (median age: 66 years). 23%, 37% and 40% of diagnosis were performed between 2001-2004, 2005-2008 and 2009-2012 respectively. Variability was found for the presence of constitutional symptoms (from 43% in PET-MF to 49% in PPV-MF); an excess of splenomegaly emerged in PPV-MF cohort (84% vs 74% and 75% in PMF and PET-MF respectively). Mean value + SD of Hb, WBC and PLT were: 13.9 + 16.5 g/dl, 17.4 + 30.8 109/l, 372 + 316 109/l respectively with higher levels of Hb and WBC in PPV-MF patients than PET-MF and PMF (p3, as compared with the reference category of patients with IPSS 0-1. As shown in Figure 1, an exploratory analysis documented different patterns of predictivity when the analysis was stratified according to the diagnosis subtypes. The determinants of the prognostic value of IPSS in PPV-MF vs PET-MF (and PMF, data not shown) would certainly deserve fully adjusted analysis in prospective well defined cohorts of patients. Conclusions The intensive quality control needed to assure the reliability, representativeness and the comparability of the data across international centers with expertise in this field confirms both the interest, but also the challenge of a cooperative epidemiological effort capable of representing a knowledge producing shared resource in the area of MF and other rare disease. Based also on the methodological and operational challenge resulting from this pilot study, a prospective study has been activated starting on September 2013. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract 221 Background and aim In vivo T cell depletion with either Antithymocyte Globulin (ATG) or Alemtuzumab (Alem) for GVHD prophylaxis is frequently included in reduced intensity conditioning (RIC). We recently reported the results of two Phase II studies performed by GITMO in high risk patients undergoing allogeneic stem cell transplantation (HSCT) using an unrelated donor (UD) after conditioning with either an ATG or Alem based RIC (Rambaldi et al.: Leukemia 2012). Since both these programs proved to be well tolerated and reasonably effective we compared them in a prospective randomized Phase II clinical trial (ClinicalTrial.gov Identifier: NCT00354120). Study design and Patients The composite primary end point was the efficacy (overall and event free survival) and the safety (infectious complications and GVHD) of the two conditioning regimens. In addition, the outcome of patients receiving an UD transplant was compared (by a time dependent analysis, correcting for time to transplant) to patients who were not randomized for the lack of a donor or any other reasons. From March 2005 to September 2008, 245 patients were registered into this study when the UD search was activated. Of these patients, 121 were randomized and 112 (AML n=27, NHL n=27, HD n=26, MDS n=14, B-CLL n=11, ALL n= 4, CML n= 2, and MF n= 1) underwent HSCT (median age 58 years, range 17–67). The 2 randomized groups were well balanced. All these patients were unfit for conventional transplants due to age (between 55 and 65 years for acute leukemias, myelodysplastic syndromes, chronic myeloid leukemia and myelofibrosis) or advanced disease (for Hodgkin and non-Hodgkin Lymphomas). A previous autologous transplant was performed in 49% of patients while 26% had received more than 3 courses of chemotherapy. Patients were randomized to the following RIC programs: program A, (Melphalan 30 mg/m2, Fludarabine 90 mg/m2, TBI 200cGy and Alem 80 mg) (n= 58) or program B, (Thiotepa 10 mg/Kg, Cyclophosphamide 100 mg/Kg, Melphalan 30 mg/m2 and ATG 7,5 mg/Kg) (n= 54). At transplant, 52 patients were in complete remission (CR), 38 patients were in partial remission (PR) while the remaining 22 patients had active disease. Of the 124 patients who were not randomized, 58 stopped the UD search because of death before randomization. Of the remaining 66 patients, 31 were transplanted with an alternative program and 35 were unable to proceed to HSCT. Results The median time of neutrophil and platelet engraftment was similar in the 2 study arms (18 vs. 16 days and 18 vs. 18 days, respectively) but graft failure and graft rejection occurred most likely in arm A (9 vs. 1, p 0.036) and a better full donor chimerism in peripheral blood CD4+ cells was observed in arm B (93% vs. 68%, p 0.052). Of the 24 patients who had to be treated with DLI, 15 belonged to arm A and 9 to arm B (p 0.476). At day +100 the incidence of acute GVHD (> grade II) was slightly higher in the ATG arm (37% vs. 26%, p 0.224) but a higher incidence of late occurring acute GVHD occurred in the Alem arm, most likely because of DLI (5/6 patients, all with GVHD > grade III). The incidence of chronic GVHD was similar (40% and 41%) in both treatment arms. The immunologic reconstitution (time to CD4+ cells > 100/mcl) was slower in arm A (174 vs. 113 days, p 0.058) but no significant difference was observed in the incidence of viral, bacterial or fungal infections. A similar incidence of CMV disease (10% vs. 6% in arm A and B, respectively) and PTLD (5% in A vs. 11% in B) was observed. With a median follow up of 15 months (range 1–39), at 2 years, the non-relapse mortality (NRM) (36% vs. 35%) and the relapse rate (34% vs. 25%, p 0.294) do not differ in the 2 arms. Similarly, despite a trend for a better outcome for patients randomized to arm B, no significant difference was observed in terms of EFS (29% vs. 41%, p 0.295) and OS (36% vs. 52%, p 0,206) (Figure 1). By a multivariable model for the prediction of OS, a significant decrease of the risk of death was associated with the incidence of acute (p= 0.02) and chronic GVHD (p Conclusion A better engraftment and immune reconstitution as well as a trend for a lower relapse rate was observed in patients receiving an ATG based RIC. GVHD confirms its protective role on the risk of death confirming that an accurate dosing of in vivo T cell depleting agents is crucial for the long term clinical outcome after HSCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 746 Background The clinical benefit of high dose chemotherapy programs in patients with diffuse large B cell lymphomas (DLBCL) with unfavorable presentation (IPI>2) is still matter of debate and several prospective randomized clinical trials have been conducted to address this point. Patients and study design In year 2005 the cooperative study group GITIL launched a multicenter phase III trial (R-HDS 0305, Clinical Trials.gov.number NCT00355199) in DLBCL patients without CNS involvement and the following inclusion criteria: age between 18–60 years, stage > II B-bulk with ECOG-PS=0-3 and age adjusted IPI (aaIPI) 2–3 or age 61–65 years with ECOG-PS = 0–2 and IPI >3. The control group received 8 courses of the conventional R-CHOP-14 chemotherapy program, followed by IFRT, in patients who achieved at least a partial response (PR) after 4 cycles. Cases refractory to R-CHOP-14 could be rescued by R-HDS. The experimental arm (R-HDS) included: 3 courses of doxorubicin-containing chemotherapy (APO), followed by high-dose cyclophosphamide (CTX) 7 g/sqm, Ara-C (2g/sqm every 12 hours for 6 days), etoposide 2 g/sqm plus cisplatin 100 mg/sqm. After R-HDS chemotherapy, a mitoxantrone-melphalan (60 and 180 mg/sqm, respectively) or BEAM conditioning regimen with autologous stem cell transplantation (ASCT) + IFRT, as above. Rituximab (375 mg/sqm) was given for a total of 6 doses, twice after CTX and Ara-C based cycles, as in vivo purging before CD 34+ cells harvest, and twice after ASCT (Tarella C. et al Leukemia 21:1802–1811, 2007). The primary end-point of the study was to test an increase of 2-year Event Free Survival (EFS) from 50% in the R-CHOP arm to 65% in the intensified R-HDS arm. Secondary end-points were Disease Free Survival (DFS), Overall Survival (OS) and toxicity. Results From June 2005 to June 2011, 248 patients were enrolled in the study (R-CHOP-14=127; R-HDS=121) and 241 were evaluable as to completeness of information. The median age was 51 years (range, 18–65), 32 subjects (13.3%) had> 60 years and the M/F ratio was 1.39. Clinical features were as follows: advanced Ann Arbor clinical stage (93%), BM infiltration (22%), bulky disease (69%), elevated LDH (87%), elevated beta 2-microglobulin (60%), poor ECOG-PS (61%), B-symptoms (57%), ≥2 extranodal sites (71%), IPI 2 (51%) and IPI >3 (49%). The two arms were well balanced for all these features. No significant difference could be detected in the response rates of patients treated with R-CHOP and R-HDS that in detail, were the following: complete response (CR, 76% vs. 76%), partial response (PR, 4.7% vs. 7.9%), progressive disease (PD, 15% vs. 8.8%), stable disease (SD, 1.6% vs. 0.9%), treatment discontinuation for any reason (0 vs. 1.8%), early death (ED, 2.4% vs. 4.4%). On the contrary, the relapse rate was higher in the R-CHOP vs. the R-HDS arm (14% vs. 4.6%, p= 0.025). After a median follow-up of 27.7 months (range 0.3 – 52.5) the 2-year DFS of patients treated with R-CHOP or R-HDS is 83% vs. 93% (p=0.07) while the EFS is 68% vs. 73% (p= 0.345) (Figure 1 and 2). Similarly, with the current follow up, no significant difference could be detected in OS (77% vs. 80%, p= 0.398). The OS was better for patients with IPI 2 in comparison to those with IPI >3 (84% vs. 73%; p= 0.04), but without any significant difference according to treatment arm. Although the rate of death in remission (2% in both arms) was similar, the overall toxicity of the R-HDS arm was higher in terms of hematologic toxicity (CTC G>2) (p Conclusion In DLBCL patients with unfavorable presentation a conventional R-CHOP and a more intensive R-HDS chemotherapy achieved the same excellent rate of response. Despite a trend for a better DFS observed in patients treated with R-HDS, the EFS (primary endpoint of the study) and the OS are not different. A longer follow-up is needed in order to definitively rule out the role of intensified R-HDS program as first line treatment for poor-prognosis DLBCL patients. Disclosures: Tarella: Hoffmann-La Roche: Consultancy, Honoraria. Gianni:Hoffmann-La Roche: Consultancy, Honoraria. Pizzolo:Hoffmann-La Roche: Consultancy, Honoraria. Rambaldi:Hoffmann-La Roche: Consultancy, Honoraria.

Background Metabolic syndrome (MS) is associated with late-onset diabetes. However, diagnostic criteria for individual components of MS are based on categorical/arbitrary cut points and, therefore, do not exploit the information yield of each factor. We aimed to generate a diagnostic score for MS (MS-Score), aimed at predicting diabetes by giving appropriate weight to the individual components of MS. Methods Of 11 323 patients with prior myocardial infarction and followed up for 3.5 years in the GISSI-Prevenzione study, 3855 subjects with diabetes at baseline or missing information for relevant variables were excluded. A Cox proportional hazards model including age, sex, glycemia, high-density lipoprotein cholesterol, triglycerides, hypertension, and body mass index was fitted to create a diagnostic score. A cutoff point of 28 of the score was the best compromise between sensitivity and specificity for MS diagnosis (MS-Score). The prognostic performance of the MS-Score was compared with that of the diagnostic criteria of MS, as defined by National Cholesterol Education Program Adult Treatment Panel III (MS-ATP). Results Of 7468 patients, 940 developed diabetes. The risk of getting diabetes significantly and progressively increased in the quintiles of the score reaching >6-fold higher risk in the last one. The predictive capability of MS-Score was significantly higher than that of the MS-ATP (AUC = 0.650 vs 0.587, sensitivity 67% vs 52%, specificity 63% vs 66%, P = .0002). The MS-Score, but not the MS-ATP, was significantly associated with mortality. Conclusion MS-Score improves the prediction of diabetes development by using the full informative content of individual components for diagnosis of MS.

Abstract 1750 The Myeloproliferative Disorder-Research Consortium (MPD-RC) designed the first US prospective phase II study of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary myelofibrosis (PMF) or MF secondary to essential thrombocythemia (ET-MF) or polycythemia vera (PV-MF). Between May 2007 and March 2011, 66 patients were entered into the MPD-RC 101 study. Thirty-two patients received an allogeneic HSCT from a related and 34 patients from an unrelated donor. In the two groups diagnoses were: PMF: 44%, 74%; ET-MF: 47%, 12% and PV-MF: 9%, 15%, respectively. A reduced intensity regimen with fludarabine/melphalan (FluMel) ± ATG was used. Of 66 patients, 63 were at intermediate/high risk according to Lille score system and 3 patients were at low risk but had thrombocytopenia. Recipients of related and unrelated HSCT were comparable with respect to age (median: 54 vs 55 years), gender (M/F 19/13 vs 19/15), Lille score intermediate (63% vs 68%) or high risk (28% vs 32%) and time from diagnosis to transplant (median, range: 16, 1–247 vs 20, 2–341 months). At the time of transplant, 66% and 82% of patients in the related and unrelated cohorts had splenomegaly and 19% and 15% had previous splenectomy. Jak-2 V617F mutation was present in 38% and 50% and an abnormal karyotype was detected in 56% and 59% of patients with known status, respectively. Bone marrow stem cells were utilized in 19% of related and 9% of unrelated transplants, while in the remaining cases patients received peripheral blood stem cell (PBSC) grafts. Donor compatibility was assessed by molecular typing for HLA A, B, C, DRB1 and DQB1 antigens; inclusion criteria allowed enrollment with maximum 1 antigen mismatched donor. Thirty of 32 transplants (94%) in the related cohort and 25/36 (74%) in the unrelated cohort were fully matched. In transplants from related donor, engraftment of neutrophils and platelets occurred in 31/32 patients, One patient in this group experienced a secondary graft failure. In contrast, among patients in the unrelated group only 26/34 (76%) patients engrafted and of these 4 had a secondary graft failure post transplant. Median time to neutrophils > 0.5 × 109/L and platelets >20 × 109/L engraftment was: day 22 and day 28 in the related, and day 18 and day 28 in the unrelated cohort, respectively. Acute GVHD grade II-IV was observed in 37% related (grade III-IV: 12%) and in 42% unrelated transplants (grade III-IV: 21%). Based on the International Working Group criteria, in patients who were followed for at least 6 months there were 7 CR, 8 PR, and 11 CI among the 28 patients in the related group, and 5 CR, 1 PR, and 5 CI among the 16 patients in the unrelated group. After a median follow-up for survivors of 24 months, 25 patients (78%) in the related group are alive, 6 patients (18%) died for causes related to transplant (GVHD n=3, cardiac toxicity n=1, renal failure n=1, secondary cancer n=1) and 1 (3%) for progression of disease. In the unrelated group, 15 patients (44%) are alive at 12 months follow-up for survivors, 18 patients (53%) died for causes related to transplant and 1 patient (3%) due to relapse. Median survival time has not been reached in the related transplant group and is 7 months in the unrelated group (hazard ratio 4.2, 95% CI: 1.7–10.1, p Disclosures: No relevant conflicts of interest to declare.