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Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.Methods: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for >= 6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP).Results: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year fol low-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP.Conclusion: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.

Background Ruxolitinib (Ruxo), an orally bioavailable and selective inhibitor of JAK1 and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea (HU) might improve hematological response. Aims: To evaluate the efficacy and safety of Ruxo and HU combination. Methods This observational multicenter study, conducted from April 2012 to April 2017, enrolled 20 adult patients with a confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (PPV-MF), or post-essential thrombocythemia (PET-MF) with hyperproliferative manifestations of the disease not controlled by Ruxo therapy. All patients we enrolled into the study had received Ruxo at a starting dose based on baseline platelet count. Patients were included into the study when Ruxo proved to be unable to reduce WBC and/or platelet count to within normal range (WBC Results The addition of HU was started after a median time of ruxolitinib monotherapy of 6.5 months (range 1-49.6 months): 17 patients (85%) started HU treatment due to lack of WBC control, whereas the remaining 3 patients (15%) started for the lack of platelet control. While on Ruxo monotherapy, ten patients (50%) needed a dose reduction due to hematological toxicity and three patients temporarily discontinued Ruxo due to severe thrombocytopenia (15%). After 14.5 months (range 2-195) median time of combination therapy in 8 patients the Ruxo daily doses increased (mean increase = 5.1 mg BID), in 9 the dose was unchanged despite the addition of HU, and only in three cases the ruxolitinib dose had to be reduced (mean reduction = 3.4 mg BID). Overall, the mean daily dose of Ruxo administered to the whole cohort of patients increased by 1.8 mg BID (P=.013), and only one patient had to discontinue Ruxo, due to severe thrombocytopenia. Non-hematological adverse events were not observed. Among the 17 patients who started combination therapy to control WBC count, 14 (82.3%) obtained a WBC response, whereas, among the three patients who started HU in association with Ruxo in order to reduce platelets count, two (66.6%) achieved a platelet response. In addition, 12 patients of the whole study cohort had clinical improvement in MF-associated symptomatic burden, with 9 of them showing spleen and symptoms response and the remaining three only spleen response. Thus, a clinical response of any type was obtained in 8 patients (40%) during Ruxo monotherapy and in 17 patients (85%) during Ruxo-HU combination (P=.003). Of note, all 8 patients in which Ruxo dose was increased during combination had at least one type of drug-related clinical response. Conclusion In conclusion, the combination of HU with Ruxo yielded a high clinical response rate and increased Ruxo exposure in patients with hyperproliferative forms of MF. The association was very well tolerated, and the hematological toxicities mostly and were generally manageable with dose reductions and/or supportive treatment. Disclosures Pane: AMGEN: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau.

Plasmablastic multiple myeloma is an uncommon morphological variant of multiple myeloma with aggressive clinical course and poor outcome. Its differential diagnosis includes plasmablastic lymphoma, a variant of diffuse large B-cell lymphoma with frequent extranodal presentation, which usually affects immunosuppressed patients and is virtually indistinguishable from plasmablastic multiple myeloma on the basis of histology solely. Differential diagnosis relies on close clinical-pathological correlation. Herein, the authors report a case of aggressive multiple myeloma occurring in a 48-year-old patient with pure plasmablastic morphology, expression of T-cell markers CD3 and CD4, and cutaneous involvement as first presenting sign. Heterotopic expression of T-cell markers has been described in literature for both plasmablastic multiple myeloma and plasmablastic lymphoma. The causative mechanisms underlying this aberrant phenotype have not yet been elucidated; nevertheless the possibility of this rare finding should be considered to avoid misinterpretations. Remarkably, despite occurring rarely, cutaneous involvement could be observed at an early stage or even be the first manifestation of disease in particularly aggressive forms of myeloma. As a consequence, the presence of cutaneous lesions should not favor a straightforward diagnosis of plasmablastic lymphoma. The importance of a correct differential diagnosis lies in its therapeutical implications.

Background: Cytotoxic regimens used in induction treatments for acute myeloid leukemia (AML) almost always include standard or high-dose cytarabine (Ara-C). During or soon after induction therapy, leukemic patients frequently develop gastroenteric complications, characterized by abdominal pain and diarrhea. The association ofthese symptoms with f and melena is typical ofnecrotizing enterocolitis (NE), a life-threathening condition that can be documented by ultrasound abdominal scan. Patients and methods: We analyzed retrospectively the clinical course of169 adult patients with AML treated by standard dose Ara-C-containing induction regimens, either by continuous venous infusion (group 1) or subcutaneous injection (group 2). Ultrasonography was employed as early diagnostic tool in a majority ofpatients with gastroenteric complications. Bowel wall thickening was accurately measured and used to confirm the diagnosis of necrotizing enterocolitis. Results: In the first group of 115 patients (median age, 51 years), gastroenteric complications were observed in 55 patients (48%), and 10 patients (9%) received diagnosis ofNE, which was fatal in four. Patients with NE had a median age older than that of patients without gastroenteric symptoms, and a more prolonged neutropenia. In the second group of54 patients (median age, 60 years), gastroenteric events were observed in 14 patients (26%), and no case of NE was recorded. Conclusions: This retrospective analysis shows that NE is a serious complication occurring mainly in patients treated by Ara-C administered as continuous i.v. infusion. The Hematology Journal (2003) 4, 346–350. doi:10.1038/sj.thj.6200304

Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis that results in peripheral cytopenias. Anemia is the most common symptom of MDS and the majority of patients become transfusion-dependent with the risk of iron overload, which may lead to cardiac, hepatic and endocrine complications. Deferasirox is an orally available iron chelator administered once-daily in transfusion-dependent patients with various chronic anemias. Its efficacy has been established in controlled clinical trials. In the present study, we describe our experience with 55 consecutive MDS patients [International Prognostic Scoring System risk score of low (n=32) or intermediate-1 (n=23)] treated with deferasirox in a routine clinical setting following Consensus Guidelines on Iron Chelation Therapy. According to WHO classifications, patients had refractory anemia (n=30), refractory anemia with ringed sideroblasts (n=16), refractory cytopenia with multilineage dysplasia (n=8) or refractory cytopenia with multilineage dysplasia and ringed sideroblasts (n=1). The median monthly transfusion requirement at baseline was 3 units. Patients received a starting dosage of 10 mg/kg/day, subsequently titrated according to serum ferritin (SF) levels which were measured monthly. Safety assessment included monitoring of liver and renal parameters and recording adverse events (AE) during treatment. At the baseline, the mean ± SD SF level was 2,362±172 ng/ml and after 24 months, the mean ± SD decrease in SF was 1,679±209 ng/ml. Sixteen patients had sustained hematological improvement meeting International Working Group 2006 criteria. One patient became transfusion-independent. No severe AE were reported. In conclusion, deferasirox therapy was effective and safe in reducing transfusional iron overload and it reduces transfusion requirement in a subset of patients.

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine–rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008–2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43–86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity

We report four patients (mean age 65 yr; range 40-77 yr) affected by acquired pure red cell aplasia (PRCA) complicating chronic lymphoid disorders and treated with anti-CD20 monoclonal antibody rituximab. Three out of four patients were given packed red cell transfusion. Steroids and recombinant erythropoietin (r-Epo) were also administered as first-line therapy without response. After a mean time of 57 d (range 23-62 d) from PRCA diagnosis, all patients received rituximab at a dosage of 375 mg/m(2)/wk for four consecutive weeks. First injection side effects of rituximab were minimal. All patients showed an increase in hemoglobin levels in response to rituximab, in one patient just after the first dose, in another patient after the second and in two other patients after the third dose. Three patients (75%) were considered in complete remission (CR) and one patient (25%) in partial remission 4 wk after the last rituximab infusion, despite a CR was obtained later (16 wk following the beginning of the therapy). Finally, at the last follow-up (mean 18.5 months, range 2-60 months), all patients were alive and in continue CR. Despite very limited in number, these results suggest that rituximab is very effective in the treatment of PRCA complicating B-cell chronic lymphoproliferative disorders.

Principally located in the outer mitochondrial membrane, the translocator protein (TSPO) is an 18-kDa transmembrane protein that is a key component of the mitochondrial permeability transition pore. TSPO is associated with a number of biological processes, including apoptosis, the regulation of cellular proliferation, porphyrin transport and heme biosynthesis, immunomodulation, anion transport and the regulation of steroidogenesis. Thus, numerous studies have proposed TSPO as a promising target for novel therapeutic agents, particularly for the treatment of cancer. In the present study, the response of 30 consecutive chronic lymphocytic leukemia (CLL) patients to bendamustine and rituximab treatment was evaluated according to TSPO expression levels. Furthermore, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels, as well as caspase-3 activity were determined. Compared with the lymphocytes of healthy donors, the 30 consecutive CLL patients exhibited increased TSPO expression levels, decreased TBARS and NO levels and reduced caspase-3 activity. Six months after the treatment commenced, the TSPO/mitochondria ratio resembled that of the healthy controls in 24/30 CLL patients. In addition, an increase in TBARS and NO levels, two markers of oxidative stress, and a potentiation of caspase-3 activity in all responder patients was observed. Notably, the six patients who appeared to be resistant to treatment also displayed higher TSPO levels, and lower caspase-3 activity and TBARS levels. These data indicate that TSPO expression may be a molecular prognostic factor in CLL patients.

BACKGROUND: The combination schedule of rituximab, fludarabine and cyclophosphamide is considered the standard therapy for fit and young untreated chronic lymphocytic leukemia (CLL) patients. However, although this therapy improves progression free survival (PFS) and overall survival (OS), it has been associated with increased toxicity: 76% of the patients experienced at least one grade 3 or 4 event. Recently, encouraging clinical results in terms of safety and efficacy have been obtained using bendamustine in combination with rituximab (R-B) in untreated CLL patients. PURPOSE: We performed a multicentre retrospective study to assess safety and efficacy of R-B in a large group of untreated CLL patients. METHODS: One hundred and thirty six untreated CLL patients were recruited from 16 Italian Institutions and included in the present analysis. The median age was 69 years (range 43–85), with 49.3% of patients older than 70 years; 53.7% of cases were male. All patients had active disease as defined by the NCI-WG, and 27.2% were at Binet stage C. FISH data, available in 86/136 cases, identified a del(17p) in 5.1% of the patients and del(11q) in 5.9%. Sixty-four patients (47.1%) had a creatinine clearance ≤70 mL/min. Fifty-six % of cases showed a WHO performance status (PS) of I-II and 61% a CIRS comorbidity index >0. RESULTS: Among the 136 patients, 90 cases (66.2%) received B at the dosage of 90 mg/m2 on day 1 and 2 every 28 days, the remaining 46 cases received B at the dosage of 70 or 80 mg/m2. R was administered at the dosage of 375 mg/m2 on day 1 of all cycles in 59.6% of cases, while 40.4% received 375 mg/m2 on day 1 of the first cycle and 500 mg/m2 on day 1 of the other cycles. A total of 725 cycles were administered with a median number of 6 cycles per patient. Eighteen patients (13.2%) required early discontinuation of therapy before the sixth cycle for serious infections (n=7), persistent hematological toxicity (n=5), grade 4 dermatological toxicity (n=3), withdrawal of consent (n=2), hypersomnia and depression (n=1). Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 25.8%, 25.8%, and 16.2% of patients, respectively. Grade 3 or 4 severe infections occurred in 6.6% of patients. The overall response rate (ORR) was 93.4%, 48 patients (35.3%) achieved a complete response (CR), 79 (58.1%) a partial response (PR), 8 (5.9%) a stable disease (SD) and in 1 patient (0.7%) no response assessment was performed due to death prior to terminating therapy. In the high-risk group with del17p, 5/7 (71.4%) cases achieved a PR and 2 a SD. Age >70 years (P=0.026) and del17p (P=0.007) were the only two parameters significantly associated with a lower response rate, while del11q and unmutated IGHV, as well as creatinine clearance 0 did not seem to impact on achievement of response. The only parameter predictive of the probability of achieving a CR was an age CONCLUSIONS: The clinical practice of the Italian centers taking part in the study confirms that chemoimmunotherapy with R-B was an effective and well-tolerated treatment for untreated CLL patients. In patients with del17p the therapy appears to be less efficacious. Disclosures Off Label Use: Bendamustine in diffuse large B-cell lymphoma. Zinzani:Genentech, inc.: Membership on an entity's Board of Directors or advisory committees.

Background. The therapeutic approach in thrombocythemic patients with Philadelphia negative chronic myeloproliferative neoplasms (Ph- MPN), in order to result cost-effective (primum non nocere), is commonly driven by the risk factors considered in the gradually updated guidelines. However, no studies were addressed to evaluate if and how the real-life therapeutic approach changed in the last decades. Objective. To evaluate, in a large series of thrombocythemic patients with Ph- MPN, the impact of clinical and biological characteristics at diagnosis on the therapeutic approach adopted before and after the publication of the Italian guidelines for essential thrombocythemia therapy [1]. Methods. The analysis considered, in the patients of the Registro Italiano Trombocitemie (RIT), the clinical and biological characteristics at diagnosis, and the treatment ongoing after 3, 6, 12, and >12 months from diagnosis (antiplatelet alone [AntiPLT]; cytoreductive alone [CYT]; CYT+AntiPLT). Results. The analyzed patients were 2418, 914 (38%) males and 1504 (62%) females, with a diagnosis (PVSG or WHO criteria) performed before and after 2005 in 51% and 49% of cases, respectively. The rate of ongoing treatment with AntiPLT, CYT, and CYT+AntiPLT increased as follows: at 3rd month 16%, 12%, and 31%; at 12th month 17%, 14%, and 39%; after 12 months 19%, 16%, and 55%, respectively. Patients treated with CYT or CYT+AntiPLT did not significantly differ in their characteristics at diagnosis. The analysis of data at the 3rd month (initial phase) showed that: 1) CYT±AntiPLT treatment, ongoing in 43% of patients, was significantly related, in univariate analysis, to male gender, older age, prior thrombosis, higher thrombocytosis, leukocytosis, higher HCT level, CVRFs, comorbidities, symptoms, splenomegaly, hepatomegaly, and bone marrow fibrosis grade >0 (no relationship with JAK2 V617F mutation, and prior hemorrhage); in multivariate analysis, it was significantly related to age >60 y, age 40-60 y, prior thrombosis, PLT >1000 x109/L, PLT 700-1000 x109/L, symptoms, and comorbidities. 2) patients with standard high risk (age >60 y, and/or prior thrombosis, and/or PLT >1500 x109/L ) were receiving CYT±AntiPLT (59%), AntiPLT (7%), and no treatment (34%). 3) patients with standard low risk were receiving CYT±AntiPLT (22%), AntiPLT (27%), and no treatment (51%). Low risk patients receiving CYT±AntiPLT had age 40-60 y (73%), CVRFs (59%), symptoms (53%), comorbidities (42%), PLT 1000-1500 x109/L (35%), PLT 700-1000 x109/L (42%), JAK2 V617F mutation (30%), WBC >10 x109/L (22%). 4) in patients receiving CYT±AntiPLT, the initial cytoreductive drug and the median age were: hydroxycarbamide (80%, 68 y), anagrelide (6%, 49 y), interferon alpha (9%, 42 y), pipobroman (2%, 72 y), busulfan (3%, 70 y). The AntiPLT drug mostly used was low dose ASA (86-90% of cases, at any age). 5) Patients diagnosed after 2005, compared with those diagnosed before, showed a higher rate of CYT±AntiPLT treatment when at standard high risk ( 64% vs 53 % p Conclusion. The initial (within the 3rd month) therapeutic approach in the thrombocythemic Ph- MPN patients of the RIT was after 2005 relatively compliant with the 2004 Italian guidelines. In fact, the rate of CYT±AntiPLT treatment in patients with standard high risk was higher than before (64% vs 53%, p [1] Barbui T et al. Haematologica 2004; [2] Harrison C et al. NEJM 2005; [3] Gisslinger H et al. NEJM 2013; [4] Passamonti F et al. Blood 2012; [5] Barbui T et al. Blood 2012 *The RIT is a project of the GIMEMA Foundation Disclosures Gugliotta: Shire : Honoraria.

BACKGROUND CA 125 is a tumor marker used for the diagnosis and monitoring of ovarian carcinoma. This marker also has been found to be increased in patients with serosal effusion derived from nonneoplastic inflammatory disease and in a few instances of advanced non-Hodgkin lymphoma with serosal involvement. METHODS CA 125 levels were tested in the serum of 15 patients with acute myeloblastic leukemia (AML) at the time of diagnosis and in 3 patients with advanced leukemia with serosal involvement. In two patients with elevated serum CA 125 levels, a CA 125 assay was performed on leukemic cells and on the supernatant fluid of short term liquid culture. RESULTS Increased serum CA 125 was found in the three patients with acute leukemia with extramedullary localization and serosal effusion, whereas it was normal in 15 AML patients tested at the time of diagnosis. CA 125 was not detectable in leukemic cell extracts nor in the supernatant fluid of primary cultures. CONCLUSIONS These results indicate that leukemic cells were unable to produce CA 125 and suggest that its elevation in the serum is likely due to a serosal inflammatory reaction caused by the leukemic infiltration. Cancer 2000;88:75–8. © 2000 American Cancer Society.

Background In essential thrombocythemia (ET) patients, history of thrombosis and age over 60 y are validated risk factors for occurrence of thrombosis during the follow-up. Leukocytosis, JAK2 V617F mutation, cardiovascular (CV) general risk factors, and male gender are candidate risk factors for thrombosis. The thrombocytosis, a constitutive abnormality in ET, is associated with both thrombotic and hemorrhagic complications. Aim To evaluate in a large cohort of ET patients the potential relationship between the thrombosis history and the main clinical and biological characteristics at diagnosis, i.e. before any interference of cytoreductive treatment. Methods A cohort of ET patients (PVSG or WHO criteria) of the Registro Italiano Trombocitemie (RIT) was retrospectively analyzed through logistic regression models. Results A total of 977 patients, 387 males and 590 females, presented at diagnosis: median age 56 y (43% with age >60 y), median PLT count 783 x 109/L (33% with low thrombocytosis, 10 x 109/L), median HCT 42.6% (high HCT: >47% in 24% of the males and >44% in 23% of the females), CV general risk factors in 69% of cases (one of smoking, hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, obesity, CV disease, familiarity for thrombosis), bone marrow fibrosis grade 0 in 67% of cases, JAK2 V617F mutation in 56% of the 399 tested patients. The history of thrombosis (arterial in 74% of cases) was reported in 194 (19.9%) patients. The history of thrombosis in univariate analysis was significantly related to: age >60 y (p 0.001), male gender (p 0.009), CV general risk factors (p 0.002), low thrombocytosis (p 0.000), leukocytosis (p 0.003), high HCT (p 0.004), and JAK2 V617F mutation (p 0.008). No relationship was found with bone marrow fibrosis. In multivariate analysis a relationship was confirmed between thrombosis history and age >60 y (p 0.023), male gender (0.046), CV general risk factors (0.039), low thrombocytosis (p 0.004), leukocytosis (0.019), and JAK2 V617F mutation (p 0.033). The rate of thrombosis history in the patients without both low thrombocytosis and leukocytosis (11%, 49/428) resulted significantly lower (p 0.0001) than in the patients with leukocytosis (24%, 54/224), the patients with low thrombocytosis (27%, 71/266), and the patients with both low thrombocytosis and leukocytosis (34%, 20/59). Conclusion In this cohort of ET patients the rate of thrombosis history in multivariate analysis is significantly related to various clinical and biological characteristics at diagnosis, including low thrombocytosis (PLT 10 x 109/L), JAK2 V617F mutation, age >60 y, male gender, and CV general risk factors. Acknowledgment this study was partially supported by the GIMEMA Foundation (Promotor of the RIT) and by the AIL Foundation. Disclosures: Gugliotta: SHIRE Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

The in vitro sensitivity of human hematopoietic progenitors to PUVA, 8-MOP and UVA alone was investigated. 8-MOP alone at final concentrations of 150, 200, 600 and 1000 ng/ml did not modify colony growth of circulating and bone marrow erythroid (BFU-E), myeloid (CFU-GM) and immature (CFU-GEMM) hematopoietic progenitors obtained from normal controls. The exposure of the same progenitors to increasing doses of UVA, up to 12 J/cm 2 , progressively decreased hematopoietic colony growth (with estimated 50% inhibition occurring at about 5 J/cm 2 ). In vitro PUVA treatment (8-MOP 200 ng/ml followed by UVA 5 J/cm 2 ) caused 90% growth inhibition of circulating and bone marrow hematopoietic progenitors. In addition, the treatment completely inhibited the formation of spontaneous erythroid colonies, obtained from 5 polycythemic patients, that are considered to be a marker of this neoplastic disease. PUVA cytotoxicity was assessed by the colorimetric MTT assay. The percentage of cell death after PUVA exposure was 29±10% for both peripheral and bone marrow mononuclear cells. Our findings indicate that 8-MOP alone is not toxic to hematopoietic progenitors whereas UVA treatment determines in vitro a dose-dependent inhibition of the clonogenic capacity of normal hematopoietic cells. PUVA treatment enhances this effect, causing a quite complete inhibition of hematopoietic progenitors colony formation from normal donors and spontaneous BFU-E colony formation from polycythemic patients.

The present management of onco-haematologic patients may require continuous infusion of cytotoxic drugs, use of drugs or concentrated ion solutions which are toxic for the endothelial wall of small vessels, infusion of large amounts of antibiotics or antimycotics, red blood cell and platelet transfusion, and not rarely parenteral nutrition. Such a complex therapy needs a vascular access by a central vein catheter (CVC) insertion. Many types of CVC are available at present: tunnelled Hickman or Hickmanlike catheters, subcutaneous ports, tunnelled catheters with Groshong valve, external untunnelled catheters.

Background: the Registro Italiano Trombocitemia, that is a GIMEMA project, has been activated to registry Italian Essential Thrombocythemia (ET) patients, to improve the diagnosis appropriateness (WHO criteria), to verify the prognostic value of the clinical and biological parameters, to evaluate the compliance to the therapeutical Italian guidelines (1), and to create a network for activation of new studies. Objective: this analysis is mainly devoted to describe the ET patients registered in the RIT and to evaluate the therapeutic approach adopted in the 102 participating hematological centers. Material and methods: two thousand and fifteen ET patients have been registered after the written informed consent was obtained, and data validation by various expert panels is in progress. This preliminary report considers 1785 patients, diagnosed mainly (1078, 60.4%) since the publication in the year 2004 of the ET therapy Italian guidelines (1). Results: the patients, 678 (38%) males and 1107 (62%) females, showed at diagnosis: age 60.3 ± 16.8 years with higher values in males than in females (61.7 ± 15.3 vs. 59.4 ± 17.7, p Conclusion: in the analyzed patients of the ET Italian registry the diagnosis appropriateness resulted improved in the cases observed since the year 2004 respect those observed before, with an increase of bone marrow biopsies from 51% to 68% of patients. Moreover, in accord with the ET therapy Italian guidelines, the use of the cytoreductive drugs was less frequent in the patients diagnosed since the year 2004 than before (particularly for BUS, IFN, and ANA) and the more safe molecules IFN and ANA were preferentially deserved to the younger patients.

Epidemiological, diagnostic, prognostic and therapeutical data were retrospectively obtained by the Italian Registry in over 2000 Essential Thrombocythemia (ET) patients who mainly were diagnosed according to the PVSG criteria and were treated with potentially leukemogenic drugs. The Registro Italiano Trombocitemie (RIT), that is a GIMEMA project, has been activated in order to registry italian ET patients, to improve the diagnosis appropriateness (WHO criteria), to promote the acquisition of biological data, to evaluate the compliance to the therapeutical guidelines of the Italian Society of Hematology (SIE), to monitor in particular the ET patients receiving Interferons alpha and Anagrelide, to evaluate cases of pregnancy, pediatric age and familiarity, to define the prognostic value of the biological factors as JAK2 mutation, clonality, etc, to create a network for activation of new clinical and biological studies. The RIT, co-ordinated by the Hematology Unit of Reggio Emilia, is a web based registry that beside a public area comprehends a database of italian ET patients. The data, with respect of the privacy rules, are object of validation and analysis by various RIT expert subcommittees. Eighty hematological Institutions adhered to the RIT and 801 patients have been registered since June 2005. The ET diagnosis was done according to the PVSG (90%) and WHO (10%) criteria. The patients, 492 females and 309 males, had age 70 yr (30%), and the median age was 59 years. At diagnosis the platelet count was >1000 ×109/L in 29% of cases (mean 932). Few patients had prior thrombosis (4%; major 2%) and prior hemorrhage (2.6%). Patients at high risk of thrombosis were 55% on considering age >60 yr and/or previous thrombosis and/or PLT count >1500 ×109/L, and 65% on considering the PLT count cut-off of 1000 ×109/L. The patients shown general thrombotic risk factors (70%), disease related symptoms (40%) and splenomegaly (25%). By applying the WHO diagnostic criteria, the picture of true ET was found in 27% of cases. Sixty pregnancies have been reported. Aspirin was administered in 72% of patients and cytoreduction was performed in 62% of them, with use of Hydroxyurea (65%), Anagrelide (10%), Interferons alpha (10%), Pipobroman (4%), Busulfan (2%). A separate analysis for patients treated with Anagrelide and Iterferons alpha is in progress. To improve the diagnostic approach, the RIT has promoted the bone marrow biopsy revision (WHO criteria) and the acquisition of the new biological parameters.