ALBERT

Description: Background Venous thrombosis (VT) frequently complicates the clinical course of cancer. Reported incidence of VT in many hematological neoplasms is up to 10%, a value comparable to that of solid tumors. Available data on the incidence and management of VT in Acute Leukemia (AL) are scanty and quite discordant. We have performed a multicenter retrospective study with the primary objective to evaluate the incidence of venous thrombotic complications in a population of patients with AL. Secondary objective was to evaluate the management of these complications in patients with AL. Materials and Methods Available clinical records of out and in-patients diagnosed with AL from January 2008 to June 2013 in 4 Regional Reference Hospitals were analyzed. Cases of venous thrombosis (VT), including thrombosis in atypical sites [Retinal occlusion (RO) and Cerebral Sinus Thrombosis (CST)], were reported in the current study. All data were recorded in a dedicated database. Available laboratory tests at diagnosis of VT included complete blood cells count (CBC), basal coagulation tests (PT, aPTT, fibrinogen), Antithrombin, anticoagulant Protein S and C and D-dimer. Instrumental Diagnosis of deep vein thrombosis (DVT), pulmonary embolism (PE) and RO and CST was performed according to ACCP guidelines. In the statistical analysis, logistic regression model was applied. Fisher’s exact test was used to determine relationships between categorical variables. All P-values represented were two-sided, and statistical significance was declared when P〈 0.05. Results Over a population of 831 patients with AL, 37 cases of VT were recorded, mainly (34/37 cases) in hospitalized patients: 24 cases were associated with Acute Myeloid Leukemia (AML) and 13 with Acute Lymphoblastic Leukemia (ALL). In the cohort of patients with VT, 23 were males (14 with AML, 9 with ALL) and 14 females (4 with AML, 10 with ALL), with a mean age of 46 ± 13,1 years; mean age of patients with AML and VT was 49 ± 12,8 years; mean age of patients with ALL and VT was 40,2 ± 12,2 years. Twelve patients presented at least a concomitant chronic disease; no one was receiving anticoagulant prophylactic treatment with low molecular weight heparin (LMWH) during hospitalization. There were 23 cases of DVT of upper arms, 9 cases of proximal DVT of limbs (one complicated with PE), 2 cases of RO, 1 of CST and 1 case of intracardiac clot. In 28/37 (75,6%) cases of recorded VT, a central venous catheter (CVC) was placed (Figure 1); moreover, 21/23 events of DVT of upper arms were significantly associated with a CVC insertion (p〈 0.01). In the other 2 cases, one patient had a bulky mediastinal disease and 1 was diagnosed with promyelocytic AML. VT occurred during chemotherapy (CHT) in 32/37 (86.4%) cases, the remaining 5 cases were diagnosed in concomitance with leukemia: in 20 cases, VT occurred at induction, in 7 at consolidation and in 5 during salvage CHT. In both subgroups with VT, there was no statistical significant difference between time at diagnosis of VT and time at diagnosis of AL. At CBC, thrombocytopenia was the most frequently observed laboratory abnormality. Basal coagulation tests and anticoagulant levels were normal in all cases. Inherited prothrombotic mutations were available only for 9/37 cases, 1 case was heterozygous for Factor V Leiden and 1 for Factor II (G20210A) mutation. Most VT episodes (32/37) were treated with LMWH at therapeutic doses for the first month after diagnosis, a dose reduction was recorded in the following months, mainly related to severe thrombocytopenia after CHT ; 1 case was treated with unfractioned heparin; four cases did not receive any treatment due to severe thrombocytopenia. No cases of VT–related deaths nor fatal complications during treatment for VT were recorded. Treatments with LMWH lasted from 3 to 6 months. All patients clinically recovered from VT, only 2 late recurrences (PEs) were observed. Conclusions The incidence (4.5%) of VT in the analyzed cohort of patients with AL is almost similar to only one previous report, even if the involved sites distribution appears quite different. In particular, RO has never been reported. Atypical sites VT must be suspected to be correctly diagnosed and treated. Anticoagulant treatment schedules and duration in patients with AL is influenced by many factors, mainly related to CHT and severe thrombocytopenia. The optimal management of VT in patients with AL requires further, prospective studies. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2803 Poster Board II-779 Background. The rate of asymptomatic amyloidosis (asym-amyloidosis) detected in patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. This topic is significant because unrecognized AL may be associated with increased mortality may change the patient's management. The objective of the present investigation was to evaluate the number and clinical significance of asym-amyloidosis in MM and SM patients at the time of the diagnostic bone marrow (BM) biopsy for MM. Materials and Methods. The study population was selected from the Mayo Clinic Dysproteinemia database and consisted of consecutive patients with an established diagnosis of MM or SMM without recognition of symptomatic AL. Bone marrow biopsies at diagnosis of MM or SMM were retrospectively stained with Congo Red and reviewed by a single pathologist. A patient was considered to have asym-amyloid if Congo Red staining with apple green birefringence was found. Results. Biopsies from 144 (M 84, F 59) patients were evaluated: 77 had a diagnosis of MM and 67 of SMM. The median age was 59 (range 26-84) years. No differences were found regarding hemoglobin, platelets, prothrombin time, serum and urine proteins, serum albumin, alkaline phosphate, creatinine and β2-microglobulin among MM and SMM patients. At a median follow-up 76 months (range 0-216), 32% patients were alive, 65% dead and 2.7% lost to follow-up. Immunoglobulin isotypes were as follows: 96/144 (67%) had IgG 23/144 (16%) IgA, 12/144 (8%) had light chain only, 1/77 (1%) had IgD, none had IgM and 12/144 (8%) had biclonal or indeterminate; 84/144 (58%) were κ restricted. The presence of amyloid was found in only 2 cases (1%, 95% CI – 0.6 to 3.2), 1 in MM and 1 in SMM group. Neither of these patients had or developed signs or symptoms suggestive of organ involvement by amyloid. Among the 142 other patients without amyloid deposition in their index bone marrow, 1 (0.7%, 95% CI -0.6 to 2.0) developed symptomatic AL after 119 months of follow-up. Characteristics of these three patients are shown in table 1. Conclusions. We found only 2 cases (1%) of amyloidosis in the 144 cases of MM or SMM. Our estimates are lower than the rates which have been reported by others, perhaps because of our high level of suspicion for amyloid at our Amyloidosis Center. These data do not support the need for searching for asym-amyloidosis in patients with newly diagnosed MM or SMM as long as they have no clinical features of AL. Disclosures: Off Label Use: Hydroxyurea use in myelofibrosis. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Witzig:Novartis: Research Funding. Kumar:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 190 Type and duration of anticoagulation is still matter of debate in cancer patients with acute Deep Vein Thrombosis (DVT) of the lower limbs. Residual Vein Thrombosis (RVT) has been proven to be effective for assessing the optimal duration of oral anticoagulants in non cancer patients (Siragusa S et al Blood 2008:112:511-5). In the present study we evaluate the role of a RVT-based management of anticoagulation with Low-Molecular Weight Heparin in cancer patients with acute DVT. Materials and Methods. Patients with active cancer and a first episode of DVT were treated with LMWH for 6 months (the first month at full dosage followed by dose reduction of 25% in the next 5 months). At the end of treatment, they were managed according to RVT findings: those with RVT were randomized to continue anticoagulants for 6 additional months (Group A1) or to stop it (Group A2), while patients without RVT stopped LMWH (Group B). Outcomes were recurrent venous thromboembolism and/or major bleeding; patients were followed up for one year after LMWH discontinuation. Results. Over a period of 36 months, 409 patients were evaluated; 62 were excluded (refusal, need for continuing anticoagulation, etc). In total, 347 were included in the study (Table 1). RVT was detected in 242 (69.7%) patients; recurrent events occurred in 21.9% of those randomized to discontinue and 14.2% of those who continued LMWH. In patients without RVT (105, 30.3%), recurrent events occurred in 3 cases (2.8%) (Table 2 and Figure 1). The adjusted Hazard Ratio (HR) for age and sex between RVT groups (Group A2 vs A1) was 1.58 (95% confidence interval [CI], 0.85–2.93; P=.145). The adjusted HR between group A1 versus RVT-negative group (B) was 4.54 (CI 2.3–6.66; P =.028). Five major bleeding events occurred in Group A1 and two events both in Group A2 and B (Table 2). Overall, 89 (25.6%) patients died due to cancer progression after a median follow-up of 10.2 months after heparin withdrawn. Conclusions. The Cancer DACUS is the first ever study evaluating an individual marker for assessing duration of anticoagulation in active cancer population. Final results of the study show that absence of RVT identifies a group of patients at low risk for recurrent thrombosis who can safely stop LMWH after 6 months. Disclosures: No relevant conflicts of interest to declare.

Description: Type and duration of anticoagulation is still matter of debate in cancer patients with acute Deep Vein Thrombosis (DVT) of the lower limbs. Residual Vein Thrombosis (RVT) has been proven to be effective for assessing the optimal duration of oral anticoagulants in non cancer patients (Siragusa S et al Blood2008:112:511-5). In the present study we evaluate the role of a RVT-based management of anticoagulation with Low-Molecular Weight Heparin in cancer patients with acute DVT. Materials and Methods. Cancer patients with a first episode of DVT were treated with LMWH at therapeutic dosage for 1 month followed by dose reduction of 25% in the next 5 months. At this time, they were managed according to RVT findings: those with RVT were randomized to continue anticoagulants for 6 additional months (Group A1) or to stop (Group A2), while patients without RVT stopped LMWH (Group B). Outcomes were recurrent venous thromboembolism and/or major bleeding. Results. Over a period of 18 months, 134 patients were evaluated across 12 centers in Italy; clinical characteristics and duration of follow-up are reported in the Table 1. RVT was detected in 92 (68.6%) patients; recurrent events occurred in 23.4% of those who discontinued and 15.5% of those who continued LMWH (Table 2 and Figure 1). The adjusted Hazard Ratio (HR) for age and sex (Group A2 vs A1) was 1.58 (95% confidence interval [CI], 0.85–2.93; P = .145). Of the 42 (31.3%) patients without RVT, one had a recurrence (2.3%) (Table 2 and Figure 1). The adjusted HR (B vs A1) was 4.54 (CI 2.3–6.66; P =.028). One major bleeding event occurred in each group of patients who stopped (Group A2 and B) and 2 in those who continued anticoagulation (Table 2). Overall, 31 (23.1%) patients died due to cancer progression after a median follow-up of 13.2 months after randomization. Conclusions. The Cancer DACUS is the first study evaluating an individual marker for assessing duration of anticoagulation in active cancer population. This interim analysis shows that absence of RVT identifies a group of patients at low risk for recurrent thrombosis who can safely stop LMWH after 6 months. Figure 1. Kaplan-Meyer curve for recurrent events among groups Figure 1. Kaplan-Meyer curve for recurrent events among groups Table 1. Baseline patients characteristics Group A 1 (n.45) Group A 2 (n.47) Group B (n.42) P value* *P value refers to chi-squared test unless specified. ^Time from randomization (6 months after the index Deep Vein Thrombosis) #Active cancer at the time of diagnosis Female sex (%) 22 (48.8) 23 (48.9) 20 (47.6) 0.999 Age, mean + SD (y) 58.2 ± 12.2 63.7 ± 11.1 57.8 ± 11.6 0.124 Total duration of follow-up, (y)^ 31.5 32.8 29.9 0.146 Mean follow-up, (y)^ 1.2 ± 0.56 1.1 ± 0.53 1.1 ± 0.60 0.156 #Type of cancer: Gastrointestinal, n (%) 16 (35.5) 18 (38.3) 16 (38) 0.32 Genitourinary, n (%) 9 (20) 7 8 (17) 7 (16.6) 0.23 Breast, n (%) (15.5) 8 6 (12.7) 6 (14.2) 0.45 Lung, n (%) (17.7) 5 10 (21.2) 10 (23.8) 0.32 Haematologic, n (%) (11.1) 5 (10.6) 6 (14.2) 0.67 Table 2. Study Outcomes Outcomes Group A 1 (n.45) Group A 2 (n.47) Group B (n.42) P value* * P value refers to chi-squared test unless specified. ** P value refers to Fisher exact test 0.021 0.030 A1 vs B** Recurrences, n/total (%) 7/45 (15.5) 11/47(23.4) 1/42 (2.3) 0.010 A2 vs B** 0.733 A1 vs A2** Recurrences, n/100 person-year (%) 7/34.75 (20.1) 11/40.33 (27.3) 1/38.92 (2.5) 0.008 Type of recurrent VTE DVT 5 8 1 DVT + PE 2 2 0 Isolated PE 0 1 0 Subtype Controlateral 1 2 1 Major bleeding, n/total (%) 2/45 (4.4) 1/47(2.1) 1/42(2.3) 0.054** Major bleeding n/100 person-yr(%) 2/40.17 (4.9) 1/46.83 (2.1) 1/36.75 (2.7) 0.390

Description: Background: The clinical consequences of Deep Vein Thrombosis (DVT) have the potential to be serious yet are frequently unrecognized in the Intensive Care Unit (ICU). We hypothesized that both undetected and clinically evident VTE would affect the prognosis of critically ill patients Purpose: To systematically review whether a diagnosis of DVT in critically ill patients affects clinically important outcomes including length of stay, duration of mechanical ventilation and mortality. Material and Methods: Data sources used were the MEDLINE, EMBASE and PUBMED databases. Studies selected evaluated one or more of the following outcomes: duration of patient stay in hospital and in ICU, hospital and ICU mortality, and duration of mechanical ventilation. Two investigators independently extracted and reviewed data from each study; including study and patient characteristics and outcomes. Statistical heterogeneity was evaluated using the I2 statistic; Cohen’s Kappa for inter-rater agreement was used to assess inter-rater reliability. Data was pooled using the Mantel-Haenszel method and a random effects model using Review Manager. Results: Five studies were included in the systematic review. Patients diagnosed with DVT compared to those without DVT had increased ICU and hospital stay (7.3 days (95% confidence interval [CI] 1.4 to 13.2; P= 0.02) and 16.5 days (95% CI 1.51 to 30.59; P= 0.03), respectively. Duration of mechanical ventilation was increased by 3.41 days (95 % CI −1.12 to 7.94; P=0.14). Patients diagnosed with DVT also had increased relative risk (RR) for ICU mortality of 9.19 (95% CI 1.07 to 78.65, P=0.04) and a trend towards increased hospital mortality (RR 14.32 [95% CI 0.59 to 347.96, P = 0.10]). Conclusions: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including length of ICU and hospital stay and ICU mortality. Further research involving larger prospective study designs are warranted. Outcomes Study Duration of mechanical ventilation in days (DVT/NO DVT) Hospitalization length In days (DVT/NO DVT) ICU Stay In days (DVT/NO DVT) Hospital mortality rate (DVT/NO DVT) n (%) ICU mortality rate (DVT, n/NO DVT, n) Legend PEPP: positive end-expiratory pressur * IQR ** median “ [95%CI]) ^ Necessity for ventilation measured by PEEP ≥10: DVT/no DVT: 11 (42%)/37 (21%) Ibrahim
 2002 18.9±19.7/14.6±12.9M
 p=0.310 31.4±21.7/27.5± 18.2
 p=0.375 18.6±14.6/15.9±1.04
 p=0.388 8.9 (34.6%)/26.8(32.1)
 p=0.815 n/a Velmahos
 1998 Not given. ^ 49±32/31±24, p=〈 0.05 34±31/19±18, p=

Description: Abstract 4122 Background: We have previously identified sole +9, 13q- or 20q- as “favorable” and sole +8 or complex karyotype as “unfavorable” cytogenetic abnormalities in primary myelofibrosis (PMF) (Blood 2010; 115: 496). The purpose of the current study, which includes more than twice the number of patients included in previous studies, was to identify additional prognostically-relevant cytogenetic abnormalities in PMF and refine cytogenetic risk categorization for overall and leukemia-free survival. Methods: Clinical and laboratory data were collected from consecutive patients with PMF seen at our institution and in whom cytogenetic information at or within 1 year of diagnosis was available. Diagnosis of PMF and acute myeloid leukemia were according to the World Health organization (WHO) criteria. Results: A total of 433 patients with PMF were included in the current study. Median age at diagnosis was 65 years. IPSS risk distributions were low in 12% of patients, intermediate-1 in 25%, intermediate-2 in 24% and high in 39%. JAK2V617F mutational frequency was 60%. Cytogenetic findings were normal in 275 (64%) patients. Among the 158 (36%) patients with abnormal karyotype, 109 (69% of abnormal cases) represented sole abnormalities, 23 (15%) two abnormalities and 26 (17%) three or more (i.e. complex) abnormalities. In an effort to identify cytogenetic categories of similar prognosis, each one of 12 operational cytogenetic categories was separately compared with both normal and complex karyotype. Accordingly, we were able to devise a two-tired cytogenetic risk stratification with highly significant differences in overall and leukemia-free survival (Figures 1 and 2): unfavorable (complex karyotype or sole or two abnormalities that include +8, -7/7q-, i(17q), inv(3), -5/5q-, 12p- or 11q23 rearrangement) and favorable (all other cytogenetic findings including normal karyotype). Median survivals of patients with favorable and unfavorable karyotype were 5.2 and 2.0 years, respectively (p

Description: Abstract 1909 Poster Board I-932 Background: The International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) utilizes five independent predictors of inferior survival; of these, a hemoglobin level

Description: Abstract 3327 Background: Critically ill patients are at high risk of developing venous thromboembolism (VTE) during their stay in the intensive care unit (ICU) because of premorbid medical and surgical conditions. The clinical consequences of Deep Vein Thrombosis (DVT) have the potential to be serious yet are frequently unrecognized in the Intensive Care Unit (ICU). In contrast to the extensive documentation on the short and long–term outcomes of patients with DVT evaluated in other clinical settings, little is known about the clinical course of this disease in the ICU setting. We hypothesized that both undetected and clinically evident VTE would affect the prognosis of critically ill patients. Purpose: To systematically review whether a diagnosis of DVT in critically ill patients affects clinically important outcomes including length of stay, duration of mechanical ventilation and mortality. Material and Methods: MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies were selected if evaluate one or more of the following outcomes: hospital and ICU mortality, duration of patient stay in hospital and in ICU, and duration of mechanical ventilation. Two investigators independently extracted and reviewed data from each study; including study and patient characteristics and outcomes. Association between DVT and hospital and ICU mortality, and the mean difference of duration of patient stay in hospital and in ICU, and duration of mechanical ventilation in patients with and without DVT were calculated using a random-effects model (DerSimionan and Laird method). Pooled results are reported as relative risk (RR) and mean difference and are presented with 95% confidence interval (CI) and with 2-sided P values. A P value of .05 or less was considered statistically significant. Statistical heterogeneity was evaluated using the I2 statistic, which assesses the appropriateness of pooling the individual study results [22]. The I2 value provides an estimate of the amount of variance across studies due to heterogeneity rather than chance. Cohen's Kappa for inter-rater agreement was used to assess inter-rater reliability. Results: Six studies for a total of 1518 patients were included in the systematic review. Patients diagnosed with DVT compared to those without DVT had increased ICU and hospital stay (7.3 days (95% CI 1.4 to 13.2; P= 0.02) and 16.5 days (95% CI 1.51 to 30.59; P= 0.03), respectively. Duration of mechanical ventilation appeared to be increased in patients with DVT although this difference was not statistically significant (weighted mean difference: 3.41 days 95 % CI –1.12 to 7.94; P=0.14). Patients diagnosed with DVT also had a marginally significant increase in the RR of hospital mortality (RR 1.31 95%CI,0.99 to 1.74,P=0.06), and a non statistically significant increase in the RR of ICU mortality (RR 1.96; 95% CI 0.74 to 5.19; P = 0.17). Conclusions: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including length of ICU and hospital stay and hospital mortality. Further research involving larger prospective study designs are warranted. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1748 Introduction: Polycythemia vera (PV) is a chronic myeloproliferative neoplasms characterized by erythrocytosis, vasomotor disturbances, pruritus, risk of disease progression into acute myeloid leukemia or myelofibrosis and cardiovascular events, the last representing the main cause of morbidity and mortality. Since 2005 the V617F point mutation in Janus Kinase 2 (JAK2) gene gained a dominant role in determining the molecular basis and the diagnosis of PV. We compared the clinical epidemiology of the 1638 patients included in the ECLAP trial in the years 1997 to 2001, with that of a “modern” cohort of 365 PV, JAK2-positive patients included in the Italian CYTO-PV randomized clinical trial and followed from the year 2008 to 2012. Methods: Patients were eligible in CYTO-PV trial and in ECLAP study if they met WHO-2008 diagnostic criteria and the criteria established by the PVSG or Pearson/Messinezy respectively. Clinical characteristics have been compared. The incidence of major cardiovascular events (CV death plus major thrombosis [stroke, acute coronary syndrome, transient ischemic cerebral attack, peripheral arterial thrombosis, pulmonary embolism, abdominal thrombosis, deep vein thrombosis) and total CV events incidence has been evaluated. The median follow up was 31.0 months (range 0– 48.13 months) and 33.1 months (range 0–63.6) for patients included CYTO-PV and in ECLAP respectively. Results: In CYTO-PV 49.3% patients with recent PV diagnosis were included (within 2 years prior inclusion) while in ECLAP the proportion was 35.5%. Mean age at recruitment was similar for patients in CYTO-PV (64.5 yrs) and ECLAP (65.4 yrs). History of thrombosis was reported in 28.9 % vs 38.6% patients in the CYTO-PV and in ECLAP, respectively (p

Description: Introduction Cryopreservation for long term storage of platelets (PLTs) represents a clinical useful method for avoiding platelet shortage. Many studies have tried to define, in vitro and in vivo, the entity and weight of storage-related PLTs lesions with discordant results related to different methods. We have performed an in vitro prospective study to evaluate PLTs count, viability and function of buffy coat derived pooled platelet concentrates (BC-PLTs) treated with dimethyl-sulphoxide (DMSO) and cryopreserved at -80°C with an innovative patented system not requiring laminal flow hoods and external manipulations. Materials and methods Each BC-PLTs was obtained from 5 buffy coats and pooled according to standard procedures. The final PLTs concentrates were leukoreduced by filtration and transferred to a 650 mL cryopreservation kit (Promedical ®) which allowed mixing with DMSO 25% in a closed system and following removal of supernatant without further manipulations. BC-PLTs were washed prior freezing with removal of at least 84% supernatant solution, suspended in homologous plasma from 1 of the 5 donors to a final concentration of 200 mL and frozen at – 80°.Selection criteria to make BC-PLTs available for this study was pooled PLTs concentration 〉 1250 x 109/L and a blood units collection time duration shorter than 6 minutes. All the 245 donors were healthy volunteers and they did not take any medication affecting PLTs function. BC-PLTs were analyzed immediately pre-freezing (T0) and 3 months after cryopreservation ( CRY BC-PLTs). The following parameters were assayed: PLTs count (PC), mean platelet volume (MPV), pH, flow cytometry (FACS) expression of CD41a, CD42b, CD61a, CD62p, PAC-1, Annexin V PLTs surface antigens and thromboelastography (TEG). All samples were analyzed also after dilution (1:4) with homologous plasma to approximately 400 x109/L PLTs (data not shown) and for bacterial contamination (BC). CRY BC-PLTs samples were thawed in a bath at 37°C for 5 minutes and evaluated promptly. All the tests were performed according to current European recommendations. PLTs swirl was furthermore visually assessed. Results were expressed as mean +/- standard deviation (SD). Results obtained at T0 and after 3 months were compared by paired sample t-test. Differences were considered as significant at p values