bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Soluble P-Selectin and Low Platelet Count as Thrombosis Risk Markers in Glioma Patients.
Authors: Vormittag Rainer , Marosi Christine , Ay Cihan , Simanek Ralph , Schwarzinger Ilse , Preusser Matthias , Elandt Katarzyna , Zielinski Christoph C , Pabinger Ingrid 
Published: October 2019

Abstract
Abstract 2985
Poster Board II-961

Background
Glioma patients are at high risk for venous thromboembolism (VTE). However, predictive laboratory parameters have not been identified. High platelet count (PLC) and increased soluble P-selectin (sP-selectin) have been reported as risk factors in cancer patients, so we investigated sP-selectin and PLC as risk markers in glioma patients.

Methods
The Cancer and Thrombosis Study (CATS) is a prospective observational study, whose endpoint is the occurrence of objectively confirmed VTE. sP-selectin was measured in the third week after neurosurgical intervention using a human sP-selectin Immunoassay (R&D Systems®, Minneapolis, USA). Multivariable Cox regression analysis was applied to calculate hazard ratios (HR) for VTE, including PLC, sP-selectin, age, sex and type of surgery.

Results
140 patients with newly diagnosed high grade glioma were analysed (52 women; median age 54.5 years [interquartile range (IQR): 42.8-5.1]) during a median observation time of 309 (range: 3-1664) days. Twenty patients developed VTE (6 women, 14 men), of which 2 events were fatal pulmonary embolisms. The cumulative probability of VTE was 10% at six and 15% at twelve months. sP-selectin levels (ng/mL) were higher in patients with VTE compared to those without (median=51.8, IQR: 36.9–66.0 versus median=38.8, IQR: 30.7–52.1, p=0.011). Interestingly, PLC (G/l) was significantly lower in patients with (median=214, IQR: 166-248) than in those without VTE (median=255, IQR: 200-327; p=0.011). In multivariable regression analysis high sP-selectin (75th percentile: 55.1ng/mL) and low PLC (25th percentile: 198G/L) were significant risk markers of VTE (HR=3.4, 95% CI 1.3-9.0, and HR=3.3, 95% CI 1.2-8.8, respectively).

Conclusion
Our study revealed two strong predictive markers for VTE in glioma patients. Elevated sP-selectin is associated with a three-fold increased risk of thrombosis. In contrast to patients with other solid tumours, in glioma patients low PLC is associated with increased thrombosis risk.

Disclosures:
Pabinger: Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Tissue Type Plasminogen Activator Regulates Myeloid-Cell Dependent Neoangiogenesis During Tissue Regeneration.
Authors: Hattori Koichi , Ohki Makiko , Ohki Yuichi , Tashiro Yoshihiko , Nakauchi Hiromitsu , Heissig Beate 
Published: October 2019

Abstract
Abstract 3052
Poster Board II-1028
The fibrinolytic system comprises an inactive proenzyme, plasminogen (Plg), which is converted by activators such as tPA to the active enzyme, plasmin. Treatment with tissue type plasminogen activator (tPA) can dissolve blood clots and can ameliorate the clinical outcome in ischemic diseases (e.g. such as pulmonary embolism, myocardial infarction and stroke). Better survival in tPA-treated vs. placebo patients have been attributed to its effect on thrombus lysis. But the underlying mechanism how tPA improves ischemic tissue regeneration is not well understood. Bone marrow (BM)-derived hematopoietic cells have been shown to promote neoangiogenesis during tissue regeneration or cancer growth. Here we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin mobilizes CD45+/CD11b+ pro-angiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signalling. To study the role of tPA for cell-driven tissue regeneration, we choose a model of hindlimb ischemia. tPA improves cell incorporation of CD11b+ cells into ischemic tissues, and increases expression of neoangiogenesis-related genes including VEGF-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b+ cells and VEGFR-1+ cells, but not the same number of carrier-mobilized CD11b+ cells or CD11b− cells, accelerates neovascularization and ischemic tissue regeneration, showing that tPA administration had qualitatively changed CD11b+ cells and made them more angiogenic. Inhibition of VEGF-signalling suppresses tPA-induced neovascularization in a model of hindlimb ischemia. Thus, tPA mobilizes CD11b+ cells from the BM, increases systemic and local (cellular) VEGF-A, which can promote angiogenesis locally during ischemic recovery. We provide clinically relevant evidence that administration of the single agent tPA promotes ischemic tissue regeneration by recruiting pro-angiogenic CD11b+ myeloid cells, which qualitatively are more angiogenic then their PBS stimulated counterparts, and which incorporate with high efficiency into peripheral ischemic tissues. These data introduce a new paradigm in cell biology whereby fibrinolytic enzymes mediate systemic and localized effects on hematopoietic cells thereby modulating their tissue integration potential via integrin modulation and cytokine release and thus these data establish a novel role for tPA in the growing field of regenerative medicine.

Disclosures
No relevant conflicts of interest to declare.
A Cohort Study of Warfarin Administered to Achieve An INR of 2.0 to 3.0 for the Prevention of Recurrent Venous Thrombosis in Patients with An Antiphospholipid Antibody.
Authors: Song Madeline , Kovacs Michael J. , Crowther Mark A. 
Published: October 2019

Abstract
Abstract 3123
Poster Board III-60

Introduction
Despite recent evidence, controversy remains regarding the optimal method of recurrent thrombosis prevention in patients with antiphospholipid antibodies (APLA) and prior thrombosis. Specifically, although two randomized trials have supported the efficacy of “usual intensity warfarin” (administered to a target INR of 2.0 to 3.0) there remains a dearth of prospective data examining this treatment.
The aim of our study was to confirm that patients with prior thrombosis and an APLA had a low risk of recurrent thrombosis while being treated with warfarin administered to achieve an INR of 2.0 to 3.0.

Methods
We examined the annual rate of recurrent thrombosis in patients with prior thrombosis and APLA who had all been treated with OAT (oral anticoagulant therapy) to achieve a target INR of 2.0 to 3.0.
Eligible patients had to have had at least one prior objectively confirmed arterial or venous thrombosis and at least one positive standardized test for an APLA. Patients were selected from the Victoria Hospital, and follow up appointments were conducted through the hospital's thrombosis clinic. Consenting patients underwent a baseline clinical examination with the intent to be followed every six months for evidence of recurrent thrombosis, adverse consequences of anticoagulation therapy, or until death.

Results
Eighty three patients (mean age 50.5 years; 50 females) were enrolled; one patient was lost to follow up and did not contribute data to the analyses. Median follow up was 12 months (Range 5-18 months). No patients experienced a recurrent thrombotic event. 10 patients (12.2%) had a minor bleeding event (5 had significant ecchymosis, two had rectal bleeding, two had vaginal bleeding, and one had hematuria). No major bleeding events occurred. One patient had a presumed transient ischemic attack (TIA). One patient (1.2%) died during follow up due to multi-system organ failure in the context of a failing hepatic allograft.

Conclusion
Patients with previous thrombosis and an APLA have a low risk of recurrent thrombosis while having a target INR of 2.0 to 3.0. “Usual intensity warfarin” therapy appears to be an adequate method of thromboprophylaxis in these patients.

Disclosures
Crowther: BI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Artisan Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.
Results of the EmbraceAC Trial: A Head-to-Head Comparison of Warfarin with Tecarfarin, A New Anticoagulant.
Authors: Garcia David , Milner Peter G , Canafax Daniel M , Ellis David J 
Published: October 2019

Abstract
Abstract 3135
Poster Board III-72
EmbraceAC was conducted to evaluate whether tecarfarin (T) is superior to optimized warfarin (W) as measured by interpolated time in therapeutic range (TTR). T is a novel vitamin K antagonist free of CYP-based metabolism.
EmbraceAC was a 6-9 month randomized, double-blind, multicenter study of optimized W vs. T using a dose control center (DCC) and prospective genotyping in oral anticoagulation patients. Data from weekly INR monitoring was analyzed on an ITT basis. A total of 612 patients from 47 sites (94.3% warfarin experienced; 74.5% treated for AF, 15.7% for DVT/PE, 14.2% for cardiomyopathy/MI, and 15.5% for heart valve) were randomized (305 to W, 307 to T). Mean interpolated TTR was 73.2% for W and 74.0% for T (p, 0.51). Pre-specified subgroup analyses of warfarin experienced patients, wild-type CYP2C9 patients, and on-treatment analysis all showed statistically significant superiority of T over W. For the 31% of patients taking drugs that inhibit CYP2C9, the observed TTR for W decreased, whereas the TTR for T remained steady. There was no significant difference in the composite of clinical outcomes (death, stroke, MI, DVT, PE, or major hemorrhage): 6 for W and 8 for T (p, 0.41). Tolerability was good with both treatments and there were no differences in overall AE rate. TTR for W was exceptionally high, perhaps as a result of frequent monitoring, availability of accurate and timely genotype information, close surveillance by the DCC and early dose adjustment for potential interacting drugs. Statistical superiority of T was not established in the primary end point. As hypothesized for a drug designed to avoid CYP metabolism, T showed a significant advantage over W for patients exposed to CYP2C9 inhibitors.
DG - Consultant to Bristol Meyers Squibb, CSL Behring, ARYx Therapeutics; PM, DC, DE - ARYx Therapeutics employees.

Disclosures
Garcia: Bristol Meyers Squibb: Consultancy; CSL Behring: Consultancy; ARYx Therapeutics: Consultancy. Milner:ARYx Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Canafax:ARYx Therapeutics: Employment, Equity Ownership. Ellis:ARYx Therapeutics: Employment, Equity Ownership.
Use of Rituximab in Patients with Congenital Bleeding Disorders and High Titre Inhibitors.
Authors: Curtin Julie , Teo Juliana , Shoemark Robyn , Tatjana Kilo , Harris Catherine , Webster Boyd , Lammi Ahti 
Published: October 2019

Abstract
Abstract 3501
Poster Board III-438
The development of high titre inhibitors remains a serious complication of treatment in patients with congenital bleeding disorders. We describe a single centre experience of the use of Rituximab (monoclonal anti-CD20 antibody) in 10 patients with congenital bleeding disorders and high titre inhibitors. Nine of the patients have severe haemophilia A (Factor VIII <1%) and 1 patient has type 3 von Willebrand disease (VWD). Six patients had received previous immune tolerance therapy with various regimens prior to receiving Rituximab. Four patients with risk factors predictive of poor response to tolerisation received Rituximab as part of their initial therapy. Three of these four patients received additional immunosuppression (including intravenous immunoglobulin (IVIG) & prednisone (n=2), and IVIG, prednisone and vincristine (n=1)). Patients received cycles of weekly doses of 375 mg/m2 over 2 – 4 weeks. Four patients responded after one cycle of Rituximab therapy. The remaining 6 patients received repeated cycles of Rituximab with the frequency of cycles being between three and 12 months. These patients have to date received between 2 and 13 cycles of Rituximab over a period of up to 6 years. All patients have responded with a fall in their inhibitor titre and improvement in factor recovery. Five patients had a complete response so that they can be managed with second daily factor prophylaxis. One of these patients (the type 3 VWD patient) had a relapse 12 months after his initial response to Rituximab. He has responded to a second course of 4 doses of Rituximab. Three of the remaining five patients remain on immune tolerance induction (ITI) between 8 months and 6 years after starting Rituximab therapy. All of these patients have improved factor VIII recovery with marked reduction in bleeding frequency. Of the other two patients, 1 patient moved interstate and was no longer treated with Rituximab and the other had ITI stopped after 15 months because of poor compliance with daily factor therapy. At this time his inhibitor was undetectable and he had improved factor recovery and survival. The Rituximab was well tolerated in all patients. Four patients developed hypogammaglobulinaemia, 1 patient developed transient neutropenia, three patients had port infections, though the frequency of infection was no greater than before Rituximab therapy. This single centre of experience shows that repeated doses of Rituximab are well tolerated and has a role in the tolerisation of patients with poor response to more traditional methods of ITI.

Disclosures:
Off Label Use: Rituximab is a monoclonal antibody against CD20 that is being used for its immunomodulatory properties.
Improvement In Venous Thromboembolism (VTE) Prophylaxis In Hospitalized Cancer Patients with a Continuing Medical Educational Program In a University Hospital In South America
Authors: Conte Guillermo , Figueroa Gaston , Aranda Sandra , Araos Daniel , Gonzalez Nestor , Torres Carlos , Picarte Javier 
Published: October 2019

Abstract
Abstract 2565

Introduction:
Cancer patients have a 4 to 6-fold higher risk of suffering Venous Thromboembolism (VTE), the second cause of death in hospitalized cancer patients. These patients are considered as high risk for VTE by the ACCP guidelines, so the pharmacological prophylaxis is indicated if there is no contraindication. A study carried out at our hospital between 2003 and 2004 showed a low use of thromboprophylaxis in this group of patients. The implementation of diverse strategies may improve this prophylaxis. A continuing medical education program was introduced to medical interns and internal medicine residents between 2005 and 2009 with this purpose. The objective of this study was to evaluate changes in the use of thromboprophylaxis in cancer patients hospitalized between 2008 and 2009.

Methods:
A six-month seminar program was implemented for medical interns and internal medicine residents enhanced by daily visits to the patient rooms by the medical staff who supervised the correct use of thromboprophylaxis.
The results were based on a retrospective analysis of clinical data of medical and surgical patients diagnosed with cancer hospitalized at the University of Chile Clinical Hospital in the 2003–2004 period (Group A) and in the period 2008–2009 (Group B) (Table 1).
Exclusion Criteria at Admission: VTE diagnosis, use of anticoagulants, thromboprophylaxis contraindication and age <18 years.

Conclusion:
The risk for VTE is very high in hospitalized cancer patients and is associated with an increased risk of recurrent thrombosis. Several international medical organizations (NCCN, ASCO, ESMO, ASH) call for improving thromboprophylaxis in this high-risk population.
The introduction of an active medical educational program addressed to medical interns and internal medicine residents resulted in a significant increase in the proportion of hospitalized cancer patients who received appropriate prophylaxis in accordance with the ACCP guidelines from 65.8% at the start of the study to 86.4% (p< 0.001) after 24 months.

Disclosures:
No relevant conflicts of interest to declare.
ATG Use Is Associated with Frequent Occurrence of Positive Blood Cultures in Patients in the Early Phase After Hematopoietic Stem Cell Transplantation
Authors: Seweryn Marek , Jarosz Urszula , Krawczyk-Kulis Malgorzata , Markiewicz Miroslaw , Helbig Grzegorz , Bober Grazyna , Kyrcz-Krzemien Slawomira 
Published: October 2019

Abstract
Abstract 4564

Background:
Infectious complications remain an important cause of morbidity and mortality in the early phase after hematopoietic stem cell transplantation (HSCT).

Aim:
The aim of this study was to assess the frequency of positive blood cultures and its potential correlation with different studied parameters in large patient population studied in the first 30 days after HSCT.

Material and methods:
431 patients at median age of 47 years (range 18–85) transplanted between 2009–2011 for hematological and non-hematological malignancies were included in our analysis. There were 242 males and 189 females.

Results:
The indications for autologous and allogeneic HSCT were following: AML – 105 (24%), NHL – 86 (20%), MM – 75 (17,5%), HL – 48 (11%), ALL – 40 (9%), MDS – 17 (4%), AA – 15 (3,5%), CML – 12 (2,8%), PNH – 11 (2,6%), connective tissue diseases – 5 (1,2%), CLL – 3 (0,7%) and other – 14 (3,2%). The following transplant procedures were performed: ABCT – 213 (49%), ABMT – 3 (0,7%), alloBCT – 56 (13%), alloBMT – 21 (5%), URDBCT – 87 (20%), URDBMT – 51 (12%). Pre-transplant ATG and anti-CD52 antibody were used in 142 (33%) and 5 (1.2%) patients, respectively. Amongst 431 transplanted patients, 495 blood cultures were collected; range 0–8 (median 1). Eighty seven blood samples were positive (17,6%). The following pathogens were detected: gram-positive bacteria in 48% (n=42), gram-negative bacteria in 38% (n=33), fungi in 1% (n=1) and both G(+) and G(&minus;) bacteria in 13%(n=11). The gram-positive bacteria included: Staphylococcus epidermidis: 21 (50%), Micrococcus spp: 4 (9%), Enterococcus faecium: 3 (7%), Enterococcus faecalis: 3 (7%), Streptococcus haemolyticus: 3 (7%). The following gram-negative bacteria were found: Enterobacter cloacae: 10 (30%), Escherichia coli: 7 (21%), Pseudomonas aeruginosa: 5 (15%), Klebsiella pneumonia: 5 (15%). Candida albicans was detected only in one case. The use of ATG was associated with higher number of total blood draw and positive blood cultures. No significant correlation was found between the specific pathogen and the use of ATG. Male gender was associated with significantly higher number of blood sampling and with tendency to higher number of positive blood cultures. The type of conditioning regimen, the source of stem cell and the donor origin (auto vs sibling vs unrelated) did not influence the number of positive blood culture. There was tendency to higher number of blood intake, but not positive blood culture in patients transplanted in NR if compared to PR or CR.

Conclusions:
Positive blood cultures were positive in about 20% of patients after HSCT. Only pre-transplant ATG use was associated with the higher number of positive blood culture.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Relevance of IDH1 and IDH2 Mutations and Single Nucleotide Polymorphism (SNP) rs11554137 in Patients with Acute Myeloid Leukemia Treated with Stem Cell Transplant in First Complete Remission
Authors: Abalkhail Hala , Chaudhri Naeem A. , Walter Claudia Ulrike , Al Zahrani Hazzaa , Nounou Randa , Altombakty Ola , Almhareb Fahed , Mohamed Said , Rasheed Walid , Alsharif Fahad , Aljurf Mahmoud , Albitar Maher 
Published: October 2019

Abstract
Abstract 4643

Background:
Mutations in the genes encoding for the cytosolic isocitrate dehydrogenase 1 (IDH1) and the mitochondrial version of this enzyme (IDH2) have been reported in acute myeloid leukemia (AML) and other types of cancer. Presence of these mutations in AML correlated with more aggressive disease in some studies, but other studies did not find significant correlation with outcome when patients were treated with intensive chemotherapy. The polymorphism at rs11554137 in IDH1 was reported to correlate with inferior outcome in cytogenetically normal AML patients. Most of the studies evaluating the prognostic relevance of IDH1, IDH2 and the rs11554137 polymorphism were reported in patients treated with standard chemotherapy. The prognostic significance of these markers is not fully studied when AML patients are treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the prognostic value of the IDH1, IDH2, and rs11554137 polymorphism in patients with AML treated with HSCT in first complete remission (CR1).

Methods:
Samples from 69 patients with AML were analyzed for mutations in IDH1, IDH2, and the SNP rs11554137 by direct sequencing. All patients were diagnosed with AML, treated with chemotherapy followed by HSCT in CR1. They included intermediate (N=42) and adverse (N=27) cytogenetic risk groups.

Results:
The R132H and the SNP C to T change at rs11554137 (silent G105) in IDH1 were detected in 5 (7%) and 6 (9%) of 69 AML patients. The IDH2 mutations (N=5; 7%) included R140Q, 172K, and T169A. Patients with IDH1 or IDH2 mutations did not differ significantly in their overall survival, event free survival, or time to relapse from those without mutation. In addition, the rs11554137 SNP polymorphism did not correlate with outcome in this group of AML patients. We also looked at the combination of mutations as compared with cytogenetic risk and found no difference in survival or event free survival based on IDH1 or IDH2 mutations or rs11554137 polymorphism in the intermediate cytogenetic risk group.

Conclusion:
The data suggests that HSCT after intensive chemotherapy in CR1 may neutralize the negative prognostic impact of IDH1 and IDH2 or the rs11554137 SNP polymorphism. However, the number of cases is relatively small and further studies with larger number of cases are needed.

Disclosures:
No relevant conflicts of interest to declare.
Bortezomib Inhibit Acute Graft-Versus-Host Disease Via Shifting the Combination of T Cells Subpopulations
Authors: Weng Jianyu , Lin Shaoze , Lai Peilong , Lv Meikun , Du Xin , Ling Wei , Guo Rong , Luo Chengwei 
Published: October 2019

Abstract
Abstract 4709

Objective:
Acute graft-versus-host disease (aGVHD) confines the wider application of allogeneic bone marrow transplantation (allo-BMT), but recently studies indicate that it is possible to reduce the incidence and severity of aGVHD while preserving the GVT by using bortezomib. In current study, we explored the changes of T cell subsets after allo-BMT administrated with bortezomib immediately, in order to establish the mechanism about bortezomib attenuation aGVHD.

Materials and Methods:
BALB/c mouse were injected of 0.5 mL PBS containing C57BL/6 2×107 nucleated BM cells plus 1×107 splenocytes followed a single dose of lethal total body irradiation (TBI, 0.7 Gy/min, 8.0 Gy) with or without bortezomib at 1.0 mg/kg. The level of CD4+ CD25+ Foxp3+ regulator T cells is quantified by flow cytometry, and the cytokine level of IL-2 and IL-4 is quantified by ELISA.

Results:
Bortezomib remarkably reduce aGVHD severity and prolonged the surviving time. Along with bortezomib injection, the level of CD4+ CD25+ Foxp3+ regulator T cell is significantly increased, the cytokine level of IL-2 is decreased but IL-4 is increased.

Conclusion:
Bortezomib inhibit aGVHD through shifting the combination of T cell subpopulations with up regulation CD4+CD25+ Foxp3+ regulator T cells lead to reset Th1/Th2 cytokine balance.

Disclosures:
No relevant conflicts of interest to declare.