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BACKGROUND: In Italy, as in many developed countries, a decline in blood component (BC) consumption, especially red blood cells (RBC), has been described, but not studied at a national level. We, therefore, designed a nationwide survey to determine the main features of BC recipients and obtain a picture of the clinical use of BC for the first time in Italy, in order to understand BC demands better and identify specific fields in which to apply Patient Blood Management (PBM). MATERIAL AND METHODS: A nationwide survey of all Italian Blood Establishments working as Hospital Blood Banks (HBB) was performed. Data were collected through an online report form recording information on the number and geographic area of the responding HBB, year of birth and sex of the BC recipients, and clinical indications for every unit of RBC, platelets and plasma transfused in a 24-hour period. RESULTS: On the survey date, 153/237 (64.5%) of the HBB returned 4,356 forms, reporting 7,523 transfusions. The median and mean ages of the recipients were 73 (range, 0–106) and 67.5 years, respectively; 33.0% were >80 years old and 64.9% >65 years old, with no relevant differences between males and females. Overall, 6,309 RBC units were transfused to 3,850 recipients, 66.7% of them for a medical indication and 32.4% for a surgical indication. The commonest medical indication was acquired, non-cancer-related anaemia and more than 30% of the transfusions occurred in the Emergency Department. Five hundred and sixty platelet transfusions were given to 520 recipients, 62.7% of them for prophylaxis and 28.6% for bleeding before or during an invasive procedure or surgery or for thrombocytopenia. One hundred and ninety-four patients received 654 units of plasma, 71.1% of which were for therapeutic purposes in bleeding patients. DISCUSSION: We collected a picture of blood transfusion epidemiology in Italy. The data suggest that future PBM plans should be focused on medical anaemia especially in the setting of Emergency Departments.

An observational prospective study was conducted by the CML Italian network to analyze the role of baseline patient characteristics and first line treatments on overall survival and CML-related mortality in 1206 newly diagnosed CML patients, 608 treated with imatinib (IMA) and 598 with 2nd generation tyrosine kinase inhibitors (2GTKI). IMA-treated patients were much older (median age 69 years, IQR 58-77) than the 2GTKI group (52, IQR 41-63) and had more comorbidities. Estimated 4-year overall survival of the entire cohort was 89% (95%CI 85.9-91.4). Overall, 73 patients (6.1%) died: 17 (2.8%) in the 2GTKI vs 56 (9.2%) in the IMA cohort (adjusted HR=0.50; 95% CI=0.26-0.94), but no differences were detected for CML-related mortality (10 (1.7%) vs 11 (1.8%) in the 2GTKIs vs IMA cohort (sHR=1.61; 0.52-4.96). The ELTS score was associated to CML mortality (high risk vs low, HR=9.67; 95%CI 2.94-31.74; p

Introduction Tyrosine kinase inhibitors (TKIs) have dramatically changed the outcome of chronic phase chronic myeloid leukemia patients (CP-CML),improving the long-term outcome; indeed, life expectancy is now very close to that of age matched individuals in the general population. Imatinib (IMA) the first generation TKI, increased the overall survival(OS)by more than 80%. Second-generation TKIs, (2gen TKIs) used in first line dasatinib and nilotinib, induced faster molecular responses, rapidly reducing the disease burden, but did not change the OS of CP-CML newly diagnosed patients. Most of the available data reported were extrapolated from sponsored clinical trials. The aim of this analysis is to detail and analyze the prognostic features influencing the OS in a large Italian CML cohort of patients prospectively enrolled in the GIMEMA CML Italian study. Methods Relevant clinical, demographic, biological and treatment-related information were web-based collected during a multicenter,observational Italian study that enrolled consecutive patients in each disease phase, at 68 Italian hematologic centers belonging to the GIMEMA network from January 2013 to June 2020. We analyzed prognostic factors influencing the OS by Kaplan Meier method and Cox multivariable models. Results A cohort of 1206 patients was prospectively analyzed, 608 of them received frontline IMA and 598 2genTKIs. Median age in the IMA cohort was 69 years (range 58-77) vs 52 years in the 2genTKIs cohort (range 41-63). The male/female ratio was 1.7 in the IMA group and 1.35 in the 2genTKIs cohort. Ninety-eight percent of patients were in CP. Results of molecular analysis of the BCR-ABL transcript at baseline showed: b2a2 in 33.1 % of patients and b3a2 in 59.9%, while an atypical transcript was found in 7%. The cytogenetic analysis at baseline showed major and minor additional aberrations in 5.7% and 1.6% of patients respectively. In the IMA cohort,according to the Sokal score, 27.7%, 57.3% and 15% of patients were stratified as low, intermediate and high risk, whereas according to the ELTS score 51.3%, 35.5% and 13.3%, of patients were classified as low, intermediate and high risk. In the 2genTKIs cohort, according to the Sokal score, 44.8%, 34.5% and 20.8%, were low, intermediate and high risk, respectively, whereas according to the ELTS score, 66.9%, 22% and 11% were assigned to the respective risk groups.The Charlson comorbidity index in the IMA cohort was 2-3 and 4-5 in 74% and 26% of patients respectively; in the 2genTKIs cohort the score was 2-3 in 89% and 4-5 only in 10% of patients. Overall, median follow-up of the whole population was 24.7 months (range 13.3-39.3).Seventy-three patients (6.1%) in the overall population died, the majority of them in the IMA cohort: 56 patients (9.2%), at median age of 80.5 years,11/608 (1.8%) due to CML-related causes. Conversely,in the 2genTKIs cohort only 17 patients (2.8%) died, at a median age of 62 years, 10/598 (1.7%) for CML-related causes. Estimated 60-months OS of the overall population was 86.4% (95% CI 81.3-90.2): 75.8% (95% CI 64.5-84) in the IMA cohort and 93.8% (95% CI 87.5-97) in the 2genTKIs group (p Conclusions In this first analysis of our study different clinical behaviors were observed among Italian hematologists, who prevalently prescribed IMA to older patients,with more comorbidities, as compared to 2genTKIs.These differences explain a better OS for patients treated with 2genTKIs vs IMA, however, the risk of death for CML related causes is quite similar between the two groups, all the differences being attributable to other causes of death.Prognostic baseline features associated to an increased OS confirmed that, in addition to age, the ELTS score and the comorbidities are the main clinical factors that independently influence the long-term OS Disclosures Pregno: Incyte-Italy,: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Novartis-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Pfizer-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports. Breccia:Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy. Castagnetti:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Galimberti:Novartis: Speakers Bureau; Incyte: Honoraria. Bocchia:CELGENE: Honoraria; Incyte: Honoraria. Abruzzese:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Levato:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rosti:Pfizer: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Di Raimondo:GILEAD, Incyte: Research Funding; Amgen, Takeda, Novartis: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Pane:Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau. Foà:Incyte: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Saglio:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Roche: Research Funding; Novartis: Research Funding; Ariad: Research Funding.

IntroductionTemporary ileostomy is a valuable aid in reducing the severity of complications related to rectal cancer surgery. However, it is still unclear what is the best timing of its closure in relation to the feasibility of an adjuvant treatment, especially considering patient-reported outcomes and health system costs. The aim of the study is to compare the results of an early versus late closure strategy in patients with indication to adjuvant chemotherapy after resection for rectal cancer.Methods and analysisThis is a prospective multicentre randomised trial, sponsored by Rete Oncologica Piemonte e Valle d’Aosta (Oncology Network of Piedmont and Aosta Valley-Italy). Patients undergone to rectal cancer surgery with temporary ileostomy, aged >18 years, without evidence of anastomotic leak and with indication to adjuvant chemotherapy will be enrolled in 28 Network centres. An early closure strategy (between 30 and 40 days from rectal surgery) will be compared with a late one (after the end of adjuvant therapy). Primary endpoint will be the compliance to adjuvant chemotherapy with and without ileostomy. Complications associated with stoma closure as well as quality of life, costs and oncological outcomes will be assessed as secondary endpoints.Ethics and disseminationThe trial will engage the Network professional teams in a common effort to improve the treatment of rectal cancer by ensuring the best results in relation to the most correct use of resources. It will take into consideration both the patients’ point of view (patient-reported outcome) and the health system perspective (costs analysis). The study has been approved by the Ethical Review Board of Città della Salute e della Scienza Hospital in Turin (Italy). The results of the study will be disseminated by the Network website, medical conferences and peer-reviewed scientific journals.Trial registration numberNCT04372992.

to assess at population level if healthcare administrative data can be suitable to identify variability and determinants of the prescribing rates for some diagnostic imaging procedures at high-risk of inappropriateness.population-based observational study.Piedmont Region (Northern Italy) adult population (20 years) in year 2013. The subjects included were 3,566,147, referring to 3,016 general practitioners (GPs), in 12 Local Health Authorities (LHAs).prescription rates of 4 diagnostic imaging procedures at high-risk of inappropriateness (vertebral and joint magnetic resonance - MR, vertebral computed tomography - CT, and bone densitometry). The following factors have been investigated: sociodemographic and clinical data of the subjects, prescribing GPs' characteristics, and organizational environment of the LHA for whom the GP is working. For each procedure, prescription rate determinants have been estimated by a logistic regression modelling of the probability of receiving at least one prescription during the year. Hierarchical data structure has been managed. The Intraclass Correlation Coefficient (ICC) and the Median Odds Ratio (MOR) were used as measures of variability due to GPs and LHAs.the degree of variability among LHAs and, within each LHA, among GPs was moderate (ICC for LHA: 0.009 and 0.004; ICC for GP: 0.015 and 0.014, respectively, for vertebral and joint MR). Prescribing probability was mainly explained by the demographic and clinical characteristics of the subjects. Most of the GPs' characteristics did not show any relevant association. Results suggest also a potential role of the private technology availability in the LHA where the GP is working.administrative healthcare data did not describe a relevant degree of variability in prescribing diagnostic imaging procedures in Piedmont Region, except for some GPs and LHAs with a different rate from the regional average. To explain differences in prescribing rates of some GPs or LHAs and to assess their appropriateness, outpatient databases should be enriched with clinical data (mainly, diagnosis or clinical suspicion) or different tools, such as clinical audit, should be used.

Purpose This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous fistula, compared to TEM alone and TEM following LCRT, which forced us to stop the study.

Growing evidence points to an association between timing of food intake and obesity in humans, raising the question if when to eat matters as much as what and how much to eat. Based on the new definition of obesity as a chronobiological disease, an unusual or late meal timing represent a circadian chronodisruption, leading to metabolic impairments. Preliminary data from cross-sectional and experimental studies suggest that changes in meal timing can influence obesity and success of weight loss therapy, independently from total energy intake, dietary composition and estimated energy expenditure. A systematic review of observational and experimental studies in humans was conducted to explore the link between time of food ingestion, obesity and metabolic alterations. Results confirm that eating time is relevant for obesity and metabolism: observational and experimental studies found an association between meal timing, weight gain, hyperglycemia and diabetes mellitus with benefits deriving from an early intake of food in the day in a wide range of individuals. Herein clinical, future perspectives of chronoprevention and chronotherapy of obesity and type 2 diabetes are also provided. In conclusion, meal timing appears as a new potential target in weight control strategies, and therapeutic strategies should consider this contributor in the prevention of obesity.

This multicenter case series introduces an innovative ultrasonic implant site preparation (UISP) technique as an alternative to the use of traditional rotary instruments. A total of 3,579 implants were inserted in 1,885 subjects, and the sites were prepared using a specific ultrasonic device with a 1- to 3-year follow-up. No surgical complications related to the UISP protocol were reported for any of the implant sites. Seventy-eight implants (59 maxillary, 19 mandibular) failed within 5 months of insertion, for an overall osseointegration percentage of 97.82% (97.14% maxilla, 98.75% mandible). Three maxillary implants failed after 3 years of loading, with an overall implant survival rate of 97.74% (96.99% maxilla, 98.75% mandible).

Background. The outcome of relapsed/refractory diffuse large-B cell lymphoma (DLBCL) patients after first line chemoimmunotherapy is poor, and the choice of the best salvage treatment is challenging. Acisplatin-containing regimen (DHAP, cisplatin, high-dose citarabine, dexamethasone) is worldwide accepted as induction pre-stem cell transplantation (SCT). Bortezomib had proven activity in aggressive lymphomas. On these bases, the Fondazione Italiana Linfomi designed the FIL-VERAL12 trial, aimed at evaluating whether the addition of bortezomib to rituximab-DHAP (BR-DHAP) increases complete response rate (CR, according to Lugano 2007 criteria) prior SCT compared to standard R-DHAP. Methods. FIL-VERAL12 was a prospective, multicenter, two-arm randomized phase II trial (NCT01805557).The primary study endpoint wasCR after 4 courses of R-DHAP or BR-DHAP, assuming a 30% CR for the standard arm and a 50% CR in experimental arm. Inclusion criteria were: patients aged 18-65 years with relapsed/refractory DLBCL after first line chemoimmunotherapy, eligible to high-dose therapy. A centrally histological review and classification according to cell of origin profile was planned. Patients were stratified by relapsed or refractory and randomized 1:1 to receive: a) the standard salvage therapy R-DHAP every 28 days for 4 cycles and b) subcutaneous 1.5 mg/sqm bortezomib on days 1 and 4 of each 4-week cycle in addition to the same regimen. Restaging, mobilization and harvesting of peripheral stem cell were performed after the second course. Results. From January 2013 to November 2018, 114 patients were screened; 108 eligible patients were enrolled into the trial and randomized to receive R-DHAP or BR-DHAP (54 patients in each arm). Principal clinical characteristics were: median age 57 years (IQR: 48;62); stage III/IV 81 patients (75%); IPI risk >3 32 (30%). All patients received rituximab and anthracycline-based regimens as first line treatment. Considering the time at relapse, 52 patients (48%) were registered as relapsed (median time at relapse 10.8 months, IQR: 6.9;20.9) and 46 (43%) as refractory (0.9 months, IQR 0.52;1.3); in the remaining 10 patients the data is missing at the time of this analysis. 51 (47%) patients completed the planned 4 cycles of therapy; 57 did not, due to progressive disease in 20, adverse events in 2, unknown causes in 35 cases. Intermediate response after 2 courses was: CR 16 (15%), partial response (PR) 37 (34%), stable disease (SD) 16 (15%); 24 (22%) were in progression (PD) and 15 (14%) were not available for response. At the end of treatment, the pre-ASCT response was: : CR 30 (28%), PR 10 (9%), SD 13 (12%), PD 38 (35%), NA 17 (16%). According to arm of randomization, the primary end point was not met, with CR 30% for R-DHAP and 26% for BR-DHAP (Pr 0.667). 38 patients performed a consolidation SCT, autologous SCT in 38, allogeneic SCT in 4. The addition of bortezomib to standard R-DHAP did not impact the mobilization: only one patient was poor mobilizer and the median number of CD34+ collected was 6.9 x 10^6 cells CD34/kg (IQR: 4.8; 9.7), with no differences between the two arms. No toxic deaths were recorded into the trial. On 294 cycles with data available, haematological and extra-haematological toxicities were: grade 3-4 neutropenia in 152 of 294 courses (52%), g 3-4 thrombocytopenia in 209 (71%); g 3-4 febrile neutropenia in 4 (1%), g3-4 infection in 5 (2%), g3-4 neurotoxicity in 5 (2%); the incidence of adverse events were similar in the two arms. At a median follow-up of 9.8 months, 12-months PFS was: overall 48.8% (38.4-58.4), 44.6% (30.4-57.8) and 53.1% (37.9-66.1) for R-DHAP and BR-DHAP, respectively (log rank, p 0.464). At a median follow-up of 15.9 months, 12-months OS was: overall 69% (58.2-77.7), 62.7% (46.4-75.3) and 75.1% (59.6-85.4) for R-DHAP and BR-DHAP, respectively (log rank, p 0.628). Conclusions. In the FIL-VERAL12 phase II randomized trial, the addition of bortezomib to R-DHAP did not improve the outcome of relapsed/refractory DLBCL patients eligible to high-dose therapy plus SCT. This series of patients is mainly represented by true refractory patients after first line chemoimmunotherapy and the results underline the poor outcome of such patients. The treatment for these patients is still an unmet clinical need. The role of immunotherapies such as the integration of CAR-T therapy in this setting of patients should be investigated. Disclosures Chiappella: Teva: Speakers Bureau; Celgene: Other: advisory board, Speakers Bureau; Janssen: Other: advisory board, Speakers Bureau; Servier: Other: advisory board, Speakers Bureau; Roche: Speakers Bureau. Corradini:Amgen: Honoraria; Janssen: Honoraria, Other: Travel Costs; Servier: Honoraria; KiowaKirin: Honoraria; Sanofi: Honoraria; Gilead: Honoraria, Other: Travel Costs; Jazz Pharmaceutics: Honoraria; Kite: Honoraria; Novartis: Honoraria, Other: Travel Costs; Roche: Honoraria; Takeda: Honoraria, Other: Travel Costs; Daiichi Sankyo: Honoraria; Celgene: Honoraria, Other: Travel Costs; AbbVie: Consultancy, Honoraria, Other: Travel Costs; BMS: Other: Travel Costs. Liberati:Novartis: Other: Clinical trial support; Janssen: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Roche: Other: Clinical trial support; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Celgene: Honoraria, Other: Clinical trial support; Bristol-Myers Squibb: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Nassi:Merck: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Vitolo:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: the use of subcutaneous bortezomib is not registered in diffuse large B-cell lymphoma. Bortezomib was provided free by Janssen

SummaryCurrent data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 “Fondazione Italiana Linfomi” (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs. Data for VTE occurrence were retrieved from study databases and pharmacovigilance reports. Our analysis includes 1717 patients from 12 prospective phase II and III trials, including newly diagnosed NHL. We observed 53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The cumulative incidences for „all-grade” or grade ≥3 VTEs were 2.9% (95% CI: 2.1–3.8) and 1.1% (95% CI: 0.6–1.6), respectively. KS categories were positively associated with the risk of VTE of any grade, and with severe events (i. e. grade ≥3; Gray’s test p-values = 0.048 and 0.012, respectively). Among NHL patients, those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any grade) VTE (HR: 3.42, 95% CI: 1.32–8.84, p-value = 0.011). Our study indicates that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of VTE events and 3) DLBCL histotype is an independent risk factor for VTE incidence, for which preventative interventions could be considered.Supplementary Material to this article is available at www.thrombosis-online.com.

Background: The advent of Tyrosine Kinase Inhibitors (TKI) totally changed the outcome of patients affected by Chronic Myeloid Leukemia (CML). Most of informations about the clinical characteristics of CML patients are based on data derived from clinical trials, that often exclude patients not fitting with strict inclusion criteria. In real life may be important to know the characteristics of the entire CML patients' population and this is better reflected by registries studies including all consecutive patients. Aim: To provide a robust and updated information on clinical, hematologic characteristics and treatment response in non-selected Italian patients with CML in each phase of the disease. Methods:We retrospectively and prospectively recorder in a web-based database clinical, hematological, cytogenetic and biological informations about all new diagnosis of CML patients referred to Italian Hematology Centers of the GIMEMA Study Group from January 2012 to June 2016. Results:Our study covered 1051 patients newly diagnosed with CML and treated between January 2012 and June 2016 in 66 Italian centers. Median age at diagnosis was 59 years (range 47-71) and 60.8% were males. At diagnosis among 908 patients 899 (99%) patients were in chronic phase, 7 (0.8%) patients in accelerate phase and 2 (0.2%) in blastic crisis. Among 1051 patients, 148 (14%), 351 (33%), 318 (30.3%) were high, intermediate and low risk by Sokal with 234 (22.2%) missing; 54 (5%), 418 (40%), 342 (32.5%) high, intermediate and low risk by EURO with 237 (22.6%) missing; 55 (5%) and 797 (76%) high and low risk by EUTOS with 199 (18.9%) missing; 96 (9%), 208 (20%), 533 (51%) high, intermediate and low risk by ELTS with 214 (20.4%) missing, respectively. The median follow-up was 36 months and 36 patients died (10 CML related). At cytogenetic analysis, there were 887 available informations: 809 (77%) without additional cytogenetic aberrations (ACA), 49 (5%) with major route and 29 (2.8%) with minor route ACA respectively. BCR-ABL transcripts among 873 data available were: b2a2 in 303 (34.7%), b3a2 in 493 (56.5%), b2a2+b3a2 in 61 (7%), e1a2 in 12 (1.4%), e19a2 in 2 (0.2%) b3a2+e1a2 in 2 (0.2%) patients respectively. ECOG performance status among 801 patients was 0, 1, or ≥ 2 in 585 (73%), 181 (22.6%) and 35 (4.4%) cases respectively. According to co-morbidity and excluding CML diagnosis as parameter, among 995 cases the Charlson comorbidity index, was 0, 1, 2 or ≥3 in 771 (73.4%), 115 (11%), 60 (5.7%) and 49 (4.7%) patients respectively; among 556 patients cardiovascular, lung, metabolic and oncologic diseases were observed in 283 (24%), 108 (10.3%), 77 (7.3%) and 88 (8.4%) patients respectively. Five hundred-ten (48.5%) and 541 (51.4%) patients were treated in first-line with imatinib (IMA) and with II generation TKI (IIGen-TKI) respectively. Three hundred twenty-one (30%) cases were pretreated with hydroxyurea. Molecular responses data at 3th month were available in 728 patients and of these 102 (14.01%) obtained at least Major Molecular Response IS (MR) MR3, 29 (3.98%) MR4, 27 (3.71%) MR4.5, 13 (1.79%) MR5 and 11 (1.5%) undetectable BCR-ABL1transcript, respectively. At 6thmonth, among 731 data available, at least 292 patients (39,57%) obtained MR3, 90 (12,19%) MR4, 75(10.16%) MR4.5, 35 (4.74%) MR5 and 29 (3.97%) undetectable BCR-ABL1transcript, respectively. At 12thmonth among 709 molecular responses available, 425 patients (59.94%) achieved at least MR3, 203 (28,63%) MR4, 171 (24.12%) MR4.5, 90 (12.69%) MR5 and 78 (11%) undetectable BCR-ABL1transcript, respectively. As showed in table 1, the IIGen-TKI were able to obtain a higher, earlier and deeper molecular response at 3th, 6thand 12thmonth than IMA. Data analysis about responses at 24thmonth are ongoing. Overall survival at 5 years was 93.4% (95% IC 90.1-95.6). Conclusions:Our preliminary results of this observational epidemiologic study suggest that collection of clinical data of CML patients treated out of strictly clinical trials represent an essential tool for long/term treatment, able to observe setting strategies based on the clinical characteristics, the degree of response obtained, and the toxicity related to the therapy in overall CML population. We are planning to continue to analyze all these endpoints to estimate the response and toxicity according to ELN guidelines, and feasibility of treatment sequence in a cohort of patients treated in real-life. Disclosures Castagnetti: Pfizer: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Breccia:BMS: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Pane:AMGEN: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau.

Survival rates for elderly Hodgkin Lymphoma (HL) have not improved substantially in recent years, mainly because of a lack of prospective randomized studies, due to difficulties in enrolling patients. Between 2002 and 2006, 54 untreated HL patients, aged between 65 and 80 years and considered 'non-frail' according to a comprehensive geriatric evaluation, were enrolled into a phase III randomized trial to compare a reduced-intensity regimen (vinblastine, cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone, bleomycin; VEPEMB) with standard ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Primary endpoint was progression-free survival (PFS). Seventeen patients were in early stage (I-IIA), while 37 were advanced stage. Median age was 72 years and median follow-up was 76 months. Five-year PFS rates were 48% vs. 70% [adjusted Hazard ratio (HR) = 2·19, 95% confidence interval (CI) = 0·94-5·10, P = 0·068] and 5-year overall survival (OS) rates were 63% vs. 77% (adjusted HR = 1·67, 95% CI = 0·69-4·03, P = 0·254) for VEPEMB compared to ABVD. Overall treatment-related mortality was 4%. World Health Organization grade 4 cardiac and lung toxicity occurred in four patients treated with ABVD versus no cases in the VEPEMB arm. Standard ABVD regimen resulted in better PFS and OS than the VEPEMB, although the differences were not statistically significant. The low toxicity of both treatments was probably attributable to stringent selection of patients based on a Comprehensive Geriatric Assessment that excluded frail patients.

Purpose To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

Introduction Azacytidine(AZA) is the current standard of care for patients with high-risk myelodysplastic syndrome (MDS) in Europe. AZA has shown a survival advantage when compared with conventional therapies and has also shown activity in IPSS lower-risk patients. However, about 40% of patients do not respond and most patients show a loss of response within 2 years. Treatment options for MDS patients who progressed while on, failed to respond to, or became intolerant tohypomethylatingagents are scarce and it has been shown that overall survival (OS) is extremely short. Objectives of this study were to describe in a cohort of real life MDS patients treated with AZA, the reasons to discontinue treatment, and to evaluate their clinical outcomes. Methods We present here the results of a real life study from a large group ofnon selectedpatients recorded in the MDS registry of FondazioneItalianaSindromiMielodisplastiche(FISM). Only patients treated with AZA from January 2009 to June 2014 were considered for the analysis. All types of conventional published schedules of AZA were allowed. The primary end point was the evaluation of OS from start of AZA treatment to the date of death from any cause. Secondary end points were clinical response, cause of discontinuation, salvage treatments and OS from discontinuation of the drug. Results Between January 2009 to June 2014 1799 newly diagnosed MDS patients were enrolled , and 420 received AZA; 271 patients received AZA as 1st line treatment, 115 patients as 2nd line treatment, 34 as a line ≥3rd. Median age was 73 years (IQR: 67-77); 261 patients (62%) were male. WHO diagnosis was RA or RARS (n=27, 6%), RCMD with or without RS (n=62, 15%) AREB-1 (n=126, 30%), AREB 2 (n=190, 45%), other subtypes (n=15, 4%). At start of AZA therapy IPSS score was low in 11 (3%), int-1 in 80 (19%), int-2 in 143 (34%), high in 54 patients (13%), and not available in 132 patients (31%). Forty-three (47%) low and int-1 risk MDS patients had a transfusion-dependent anemia. Patients received a median of 7 courses of treatment (range 3-12). Twenty-four patients (6%) received concomitant erythropoietin therapy. OS at 1 year from beginning of AZA therapy was 73% for the whole cohort (420 pts)(95%CI: 0.69-0.78), and median OS was 23 months, 25 months for patients with IPSS lower-risk MDS and 21 months for those with IPSS higher risk MDS (log-rank test: 0.72). OS after discontinuation of AZA was 8 months. Clinical response was reported according to IWG criteria only in 288/420 patients (69%); 94 patients (33%) achieved a hematological response, that was complete in 35 patients (12%) and partial in 59 (20%), 78 patients (27%) had stable disease while 116 (40%) patients did not respond. Response was achieved after a median of 6 cycles (IQR: 4-11), in both lower and higher risk MDS patients. After a median follow up of 16 months (IQR:7-35) in 97 patients (23%) AZA therapy was still ongoing and in 323 has been discontinued (77%). Interruption of treatment was due to loss of response/worsening of hematological parameters in 24 patients who achieved complete or partial response (7%) and in 20 patients with stable disease (6%). AML evolution was the cause for interruption in 105 cases (32%), death in 28 (9%), toxicity or poor compliance in only 26 (8%), while clinical decision of the treating hematologist determined interruption in 22 cases (7%). In additional 98 patients AZA was discontinued early for reasons not reported by the treating physician (30%). Of the 323 patients who discontinued AZA 10 (3%) were managed with intensive AML-like chemotherapy, 17 (5%) underwent an allogeneic HSCT, 18 (6%) received low-dose chemotherapy, 42 (14%) other treatments and 236 patients (73%) received only transfusions and other supportive therapy. Conclusions Our data confirm that AZA therapy is effective for MDS patients, both with higher and lower IPSS risk disease. Response rate is consistent with what previously reported and median OS is 23 months. The interesting observation is that at 16 months, 77% of patients had discontinued treatment, either for progression or loss of response (45% of cases) and only in 8% of cases for reported toxicity. As there are few treatment options after AZA interruption, it is important to establish the reasons other than progression yielding to a stop in therapy, in order to avoid too early discontinuation and loss of survival advantage. Disclosures Finelli: Celgene: Research Funding; Celgene: Other: Speaker fees; Novartis: Other: Speaker fees. Angelucci:Novartis oncology, celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Santini:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Astex: Consultancy; Amgen: Consultancy; Onconova: Consultancy.

Background Little information is available regarding the effect of conventional radiotherapy on glioma-related seizures. Methods In this retrospective study, we analyzed the seizure response and outcome following conventional radiotherapy in a cohort of 43 patients with glioma (33 grade II, 10 grade III) and medically intractable epilepsy. Results At 3 months after radiotherapy, seizure reduction was significant (≥ 50% reduction of frequency compared with baseline) in 31/43 patients (72%) of the whole series and in 25/33 patients (76%) with grade II gliomas, whereas at 12 months seizure reduction was significant in 26/34 (76%) and in 19/25 (76%) patients, respectively. Seizure reduction was observed more often among patients displaying an objective tumor response on MRI, but patients with no change on MRI also had a significant seizure reduction. Seizure freedom (Engel class I) was achieved at 12 months in 32% of all patients and in 38% of patients with grade II tumors. Timing of radiotherapy and duration of seizures prior to radiotherapy were significantly associated with seizure reduction. Conclusions This study showed that a high proportion of patients with medically intractable epilepsy from diffuse gliomas derive a significant and durable benefit from radiotherapy in terms of epilepsy control and that this positive effect is not strictly associated with tumor shrinkage as shown on MRI. Radiotherapy at tumor progression seems as effective as early radiotherapy after surgery. Prospective studies must confirm and better characterize the response to radiotherapy.

Background Recent studies show that the risk of VTE in NHL pts is similar to that observed in high risk solid tumors (i.e. pancreatic, ovarian cancer). VTE in NHL occurs in most cases within three months from diagnosis and can have substantial impact on treatment delivery and outcome as well as on quality of life. However few data are available on potential predictors. Aims To better clarify the epidemiology of early (within six months from treatment start) VTE in NHL we conducted a pooled data analysis of 12 clinical trials from FIL. Our analysis included basic demographic features, lymphoma-related characteristics as well the Khorana score (based on histology, BMI, platelets WBC and HB counts) which is extensively used in solid tumors to predict VTE risk. Patients and methods From Jan. 2010 to Dec. 2014, all pts with B-cell NHL enrolled in prospective clinical trials from FIL for frontline treatment were included. For 9 studies study period included the entire trial population was included. The analyses were conducted based on CRFs as well as pharmacovigilance reports. VTE definition and grading was stated according to standard criteria of toxicity (CTCAE V4.0). Cumulative incidence of VTE from the study enrollment was estimated using the method described by Gooley et al. accounting for death from any causes as a competing risk. The Fine & Gray survival model was used to identify predictors of VTE among NHL pts. Factors predicting the grade of VTE were investigated using an ordinal logistic regression model. This pooled data analysis was approved by local IRB. Results Overall, 1,717 patients belonging to 12 studies were evaluated. Eight were phase I/II or II (25% of pts) and 4 phase III (75% of pts). M/F ratio was 1.41, Median age was 57, (IQ range (IQR) 49-66). Histologies were: DLCL-B 34%, FL 41%, MCL 18%, other 6%. Median BMI was 25 (IQR 22-28). Median Hb, WBC and platelets counts were 13g/dl) (IQR 11.5-14.2), 7.1*10^9/l (IQR 5.6-10.3), 224*10^9/l (IQR 169-298), respectively. 1189 pts were evaluable Khorana score: 58% low risk, 30% intermediate risk, 12% were high risk. Human erythropoetin support was given to 9% of patients. All pts received Rituximab. Planned therapeutic programs included ASCT in 27% of pts, conventional chemotherapy in 67% a conventional chemotherapy plus lenalidomide in 6%. Overall 59 any grade VTE episodes occurred in 51 pts (2.9%), including 21 grade III-IV VTE (18 pts). None was fatal. Median time from study enrolment to VTE was 63 days (IQR: 35-110). Considering death as a competitive event the 6 months cumulative incidence of VTE was 2,2% in low risk Khorana score, 4.5% (95%IC: 2.3-6.7) in intermediate and 6.6% (95%IC: 2.4-10.8) in high risk (p = 0.012) (figure 1). Khorana score was predictive also for grade III-IV events as they were 0,7% (95% CI:0.1-1.4) in low risk and 2.0% (95% CI:0.8-3.3) in intermediate-high risk (p = 0.048). The results were similar also after excluding lenalidomide containing studies. The Fine and Gray multivariate analyses, adjusted for age and stage, showed that Khorana score (intermediate risk adjHR = 1.96; 95%IC: 0.84-4.56 and high risk adjHR = 3.81; 95%IC: 1.51-9.58) and DLCL-B histotype (adjHR = 2.58; 95% CI: 1.01-6.55) were independently associated to an increased risk of VTE. Moreover an ordinal logistical regression model indicated that the increase of one point in the Khorana score resulted in an increased risk of VTE (OR = 1.85; 95% CI: 1.23-2.79). Download : Download high-res image (130KB) Download : Download full-size image Fig. 1 . Conclusions Our results suggest that DLCL-B histotype and Khorana score are predictors of VTE in NHL. The latter might become a simple and effective tool to assess the risk of VTE in NHL. Prospective validation including also patients not eligible for clinical trials is needed.

BACKGROUND: Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone. DESIGN AND METHODS: In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1-21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months. RESULTS: The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35-68%) and 8 of 33 patients (24%; 95% CI, 13-41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5-19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%). CONCLUSIONS: These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. (clinicaltrials.gov identifier: NCT00786851).

Background. Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D (vitD) supplementation improves outcome remain controversial. Design. Studies evaluating the prognostic role of vitD and vitD receptor (VDR) in cancer patients and trials evaluating the efficacy of vitD administration on patient outcome were identified by a search of MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library through June 2010. Results. Twenty-five studies were included. A negative prognostic role for low serum vitD level was observed in five cohort studies including patients with breast cancer (one study), colon cancer (two studies), prostate cancer (one study), and melanoma (one study), but not in two studies on non-small cell lung cancer and one study on breast cancer. Three of four studies showed that VDR+ tumors carry a better prognosis than VDR− tumors, whereas VDR polymorphisms were significantly associated with prognosis in five of 10 studies. A significant interaction between serum vitD level and VDR polymorphism was observed in one study. Three randomized trials involving advanced prostate cancer patients explored the prognostic role of vitD supplementation. A meta-analysis of these trials showed no effect on survival (pooled risk ratio, 1.07; 95% confidence interval, CI, 0.93–1.23), with strong heterogeneity among studies. Conclusion. Hypovitaminosis D seems to be associated with a worse prognosis in some cancers, but vitD supplementation failed to demonstrate a benefit in prostate cancer patients. The currently available evidence is insufficient to recommend vitD supplementation in cancer patients in clinical practice.

e17059 Background: The role of CT for RMSGM is palliative only. In this abstract we report multivariate analysis of clinical characteristcs impact on survival. Methods: We enrolled 108 pts. Five pt...

Background and rationale. Recent studies show that the risk of VTE in NHL pts is similar to that observed in high risk solid tumors (i.e. pancreatic, ovarian cancer). VTE in NHL occurs in most cases within three months from diagnosis and can have substantial impact on treatment delivery and outcome as well as on quality of life. However few data are available on potential predictors. To better clarify the epidemiology of early (within six months from treatment start) VTE in NHL we conducted a pooled data analysis of 12 clinical trials from FIL. Our analysis included basic demographic features, lymphoma-related characteristics as well the Khorana score (based on histology, BMI, platelets WBC and HB counts) which is extensively used in solid tumors to predict VTE risk. Patients and methods. From Jan. 2010 to Dec. 2014, all pts with B-cell NHL enrolled in prospective clinical trials from FIL for frontline treatment were included. For 9 studies study period included the entire trial population was included. The analyses were conducted based on CRFs as well as pharmacovigilance reports. VTE definition and grading was stated according to standard criteria of toxicity (CTCAE V4.0). Cumulative incidence of VTE from the study enrollment was estimated using the method described by Gooley et al. accounting for death from any causes as a competing risk. The Fine & Gray survival model was used to identify predictors of VTE among NHL pts. Factors predicting the grade of VTE were investigated using an ordinal logistic regression model. This pooled data analysis was approved by local IRB. Results. Overall,1717 patients belonging to 12 studies were evaluated. Eight were phase I/II or II (25% of pts) and 4 phase III (75% of pts). M/F ratio was 1.41, Median age was 57, (IQ range (IQR) 49-66). Histologies were: DLCL-B 34%, FL 41%, MCL 18%, other 6%. Median BMI was 25 (IQR 22-28). Median Hb, WBC and platelets counts were 13g/dl) (IQR 11.5-14.2), 7,1*10^9/l (IQR 5.6-10.3), 224*10^9/l (IQR 169-298), respectively. 1189 pts were evaluable Khorana score: 58% low risk, 30% intermediate risk, 12% were high risk. Human erytropoetin support was given to 9% of patients. All pts received Rituximab. Planned therapeutic programs included ASCT in 27% of pts, conventional chemotherapy in 67% a conventional chemotherapy plus lenalidomide in 6%. Overall 59 any grade VTE episodes occurred in 51 pts (2.9%), including 21 grade III-IV VTE (18 pts). None was fatal. Median time from study enrolment to VTE was 63 days (IQR: 35-110). Considering death as a competitive event the 6 months cumulative incidence of VTE was 2,2% in low risk Khorana score, 4.5% (95%IC: 2.3-6.7) in intermediate and 6.6% (95%IC: 2.4-10.8) in high risk (p=0.012) (figure 1). Khorana score was predictive also for grade III-IV events as they were 0,7% (95%IC:0.1-1.4) in low risk and 2.0% (95%IC:0.8-3.3) in intermediate-high risk (p=0.048). The result were similar also after excluding lenalidomide containing studies. The Fine and Gray multivariate analyses, adjusted for age and stage, showed that Khorana score (intermediate risk adjHR=1.96; 95%IC: 0.84-4.56 and high risk adjHR=3.81; 95%IC: 1.51-9.58) and DLCL-B histotype (adjHR=2.58; 95%IC: 1.01-6.55) were independently associated to an increased risk of VTE. Moreover an ordinal logistical regression model indicated that the increase of one point in the Khorana score resulted in an increased risk of VTE (OR=1.85; 95%CI: 1.23-2.79). Conclusions: our results suggest that DLCL-B hystotype and Khorana score are predictors of VTE in NHL. The latter might become a simple and effective tool to assess the risk of VTE in NHL. Prospective validation including also patients not eligible for clinical trials is needed. Figure 1. Figure 1. Disclosures Off Label Use: This is a metaanalysis on 12 prospective trials which employed several different experimental agents. All experimental agent will be disclosed to the audience. Luminari:Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees.