bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiometabolic Risks Among Survivors of Childhood Hematologic Malignancies.
Authors: Mulrooney Daniel A. , Kelly Aaron , Baker K. Scott , Steffen Lyn , Lunsford-Lee Jill , Petryk Anna , Sinaiko Alan R. , Dengel Donald R. , Perkins Joanna , Messinger Yoav H. , Zhou Xia , Steinberger Julia 
Published: October 2019

Abstract
Abstract 4113
Survival rates for childhood hematologic malignancies continue to improve. Research suggests these individuals are at increased risk for late adverse cardiovascular outcomes. This analysis includes children (n=101) who survived ≥ 5-yrs following diagnosis of acute lymphoblastic leukemia (ALL) (n=78), acute myeloid leukemia (AML) (n=5), and non-Hodgkin lymphoma (NHL) (n=18), compared to their frequency matched healthy siblings (n=123). Anthropometric measurements, blood pressure (BP), fasting glucose, insulin, and lipids were collected; insulin resistance was assessed by euglycemic hyperinsulinemic clamp, adjusted for lean body mass (low Mlbm represents insulin resistance); carotid artery stiffness (distensibility and compliance – low levels represent increased stiffness), adjusted for lumen diameter, was assessed by ultrasound. Least squares means and standard errors, adjusted for age, gender, pubertal development, and body mass index (BMI) were compared. Survivors (63.4% male) mean age at diagnosis was 10.3 yrs (5.7-15.8) and 15.0 yrs (9.9-17.9) at evaluation; siblings (56.1% male) were 13.6 yrs (9.0-18.0) at evaluation. Among survivors, 88 (87.1%) received chemotherapy only and 13 (12.9%) chemotherapy and cranial radiation. Metabolic syndrome (MS) (modified criteria for children) was present in 8 (7.9%) survivors vs. 6 (4.9%) siblings (p=0.35). Nevertheless, 25 (24.8 %) survivors had two or more MS components compared to 17 (13.8 %) siblings (p=0.04). There were no differences between cases and siblings on measures of adiposity (BMI, waist circumference, % body fat, visceral fat), BP, fasting glucose, insulin, and lipids. However, survivors were significantly more insulin resistant and had stiffer carotid arteries compared to controls (Table). Despite similar levels of adiposity, survivors of childhood hematologic malignancies demonstrate signs of insulin resistance and increased vascular stiffness at a young age compared to healthy controls. These findings highlight: 1) the heightened cardiovascular risk profile among children who survived hematologic malignancies and 2) that the typical components of the MS may not be sufficiently sensitive measures of risk in this young population.
Survivors (n = 101) Siblings (n = 123) (p) LS means (SE) LS means (SE) Body mass index (BMI) (kg/m2) 21.3 (0.5) 21.2 (0.5) 0.8 Visceral fat (cm3) 22.8 (1.0) 22.3 (1.0) 0.7 Insulin resistance [Mlbm (mg/kg/min)] 12.6 (0.5) 14.2 (0.5) 0.007 Carotid artery distensibility (%) 13.5 (0.4) 14.9 (0.4) 0.004 Carotid artery compliance (mm2/mmHg) 0.16 (0.004) 0.17 (0.004) 0.008

Disclosures:
No relevant conflicts of interest to declare.
Clinical Manifestation of 1000 Leukemias.
Authors: Racil Zdenek , Mayer Jiri , Brejcha Martin , Cetkovsky Petr , Prochazkova Jirina , Zounar Rene 
Published: October 2019

Abstract
Abstract 4134

Background
New available diagnostic methods could specify the diagnosis of leukemias and new drugs can improve survival of pts. with malignancy. However till today clinical manifestation continues to be the key point in diagnostic procedure of these diseases and time from the first symptoms to define diagnosis and to start of anticancer treatment is often critical for pt's. prognosis.

Methods
Documentation of 1007 consecutive pts. referred to 3 hematological centers in Czech Republic with diagnosis of the 6 most frequent leukemias between 2004-3/2009 was analyzed. Special consideration was addressed to clinical and laboratory findings and pt's. complaints before defining the diagnosis in hematological center.

Results
In 1007 pts. – 439 (44%) females/ 568 (56%) males – diagnosis of leukemia was established [ALL – 106 (11%), AML - 369 (37%), APL - 74 (7%), HCL - 41 (4%), CML - 123 (12%), CLL - 294 (29%)]. Median age at time of diagnosis was 60 years (ALL - 47, AML - 62, APL - 46.5, HCL - 59, CML - 55, CLL – 66).
Leukemia was diagnosed in 599 (59%) after first symptoms occurred and pt. visited doctor and in 408 (41%) cases accidentally. However, this accidental diagnosis occurred only in 24% pts. with acute leukemia (ALL, AML, APL) and vice-versa in 60% of pts. with chronic leukemias.
The frequency of first symptoms described by pts. shows Table 1.
The first doctor visited by patient and describing abnormality was general practitioner in 48.5%, internist in 21.8%, hematologist in 7.8% and other in 22.4%.
Median time from the first symptoms to define diagnoses was 17 days (ALL – 24, AML – 20, APL – 14, CLL – 16, CML 14, HCL – 31); median time from the first medical examination to define diagnosis was 8 days (ALL – 9, AML – 7, APL – 6, CLL – 12, CML - 6, HCL – 20) and finally the median time from the first examination by hematologist to referring pt. to hematological center was 3 days (ALL – 1, AML – 2, APL – 1, CLL – 32, CML - 8, HCL – 18).
Decision procedure of the first visited doctor was stated as inadequate in 5.5% of pts. – especially in pts with AML (9.4%). Late diagnosis influenced character of treatment and pt's prognosis in 1.5% and 1.6% of pts. respectively – mostly in pts. with acute leukemias (2.9% and 2.8%).

Conclusion
Our analysis showed that the time from the first symptoms until define diagnosis is surprisingly long although pts. with acute leukemia are very often symptomatic at the time of diagnosis. Moreover in these patients with acute leukemias (especially with AML) the diagnostic process was most frequently found as a less adequate and this could influenced the pt's prognosis.

Disclosures:
No relevant conflicts of interest to declare.
Effect of Thalidomide and Arsenic Trioxide On the Release of Tumor Necrosis Factor – α (TNF-α) and Vascular Endothelial Growth Factor (VEGF) From the KG-1a Human Acute Myelogenous Leukemia Cell Line.
Authors: Girgis Erian , Mahoney John , Khalil Rafaat , Soliman Magdi 
Published: October 2019

Abstract
Abstract 4165
Although the exact mechanism of action of thalidomide is still unknown, it has been suggested that it may affect TNF-α in addition to its possible anti-angiogenic and immunomodulatory properties. Studies conducted in our lab have indicated that thalidomide cytotoxicity in KG-1a human acute myelogenous leukemia cell line was enhanced by combining it with arsenic trioxide. So, the current investigation was conducted in order to evaluate the effect of thalidomide either alone or in combination with arsenic trioxide on the release of TNF-α and VEGF from this cell line in an attempt to clarify its possible cytotoxic mechanism. Human acute myelogenous leukemia cell line KG-1a (obtained from American Type Culture Collection, ATCC) grown in complete medium containing Iscove's modified Dulbecco's medium and fetal bovine albumin were used in this study. The cells were cultured for 48 hours in a 12 well-culture plates in duplicates at a concentration of 2×106 cells/ml in the presence or absence of thalidomide (5 mg/L) [Tocris bioscience, Ellisville, Mo] and or arsenic trioxide (4 μM) [Sigma-Aldrich, Inc., St. Louis, MO]. Cells were harvested by centrifugation and the levels of TNF-α and VEGF in the supernatant were determined by ELISA using the Quantikine TNF-α and VEGF kits respectively (R&D Systems, Minneapolis, MN). Results obtained indicate that the levels of TNF-α in the supernatant of KG-1a cell cultures incubated with both thalidomide and arsenic trioxide, whether alone or in combination were statistically lower than those observed in the supernatant of control cells (2.89 pg/ml in thalidomide treated cells supernatant, 5.07 pg/ml in arsenic trioxide treated cells supernatant and 4.15 pg/ml in case of the combined treatment with thalidomide and arsenic trioxide versus 16.88 pg/ml in the supernatant of control cells, p<0.05). However, the levels of VEGF in the supernatant of thalidomide treated cells were statistically higher than those in the supernatant of control cells (69.61 pg/ml versus 11.48 pg/ml, p< 0.001). Of note, that arsenic trioxide whether alone or in combination with thalidomide did not produce any statistically significant difference in the levels of VEGF as compared to control or thalidomide treated cell supernatant. These findings clearly indicate that both thalidomide and arsenic trioxide inhibition of TNF-α production by KG-1a cells may play an important role in their cytotoxic effect. However the increase in VEGF levels in the supernatants of thalidomide treated KG-1a cells may reflect a compensatory mechanism of cells which have survived thalidomide cytotoxicity (Supported by NIH grant RR03020).

Disclosures:
No relevant conflicts of interest to declare.
Prolonged Administration of Defibrotide Is Non-Immunogenic in Rats and Dogs.
Authors: Fareed Jawed , Hoppensteadt Debra , Cunanan Josephine , Jeske Walter , Adiguzal Cafer , Zhu He , Echart Cinara , Iacobelli Massimo 
Published: October 2019

Abstract
Abstract 4180

Introduction
Polyelectrolytes such as heparins and sulfated glycosaminoglycans are capable of interacting with endogenous proteins resulting in the generation of neoepitopes leading to the formation of antibodies such as the anti-heparin platelet factor 4 antibodies. Defibrotide represents a polyanionic, DNA derived antithrombotic/antiischemic drug which is currently used in the management of various blood and vascular disorders. Although defibrotide does not have the same protein binding profile as heparins, it mediates various cellular and plasmatic responses to produce its pharmacologic effects. The purpose of this study is to determine if the long term administration of defibrotide results in the generation of any antigenic responses in rats and dogs.

Methods
Individual groups of rats (n=24) and dogs (n=30) were administered intravenously with varying dosages of Defibrotide (0-4800 mg/kg/day in rats and 0-1600 mg/kg/day in dogs) for a 3 month period of time. At the end blood samples were drawn from each group and the collected sera were tested for the presence of anti-defibrotide, antiphospholipid and anti-heparin PF4 (HIT antibodies) using modified ELISA methods which utilized specific secondary antibodies (IgG-rat/dog conjugated to alkaline phosphatase) for the rat and dog plasmas. Blood samples collected from normal rats and dogs constituted the control group (n=30-40).

Results
Neither the rats nor the dogs treated with Defibrotide exhibited any generation of anti-defibrotide, HIT and antiphospholipid antibodies in all groups of animals tested. There was no significant difference (p>0.05) between the control and defibrotide treated animals. The average circulating levels of defibrotide were dose dependent.

Conclusion
Prolonged administration of defibrotide to rats and dogs did not result in the production of antibodies to the drug product. Moreover, there was no evidence for the generation of HIT and antiphospholipid antibodies in these studies. Therefore, unlike heparins, defibrotide administration to animals does not lead to the generation of antibodies.

Disclosures:
Echart: Gentium: Employment. Iacobelli:Gentium: Employment.
Systematic Evaluation of Coagulation Factors as Targets for Anti-Thrombotic Therapy Using Antisense Technology.
Authors: Crosby Jeff , Gao Dacao , Zhao Chenguang , Bhattacharjee Gourab , May Chris , Zhang Hong , MacLeod Robert , Monia Brett P. 
Published: October 2019

Abstract
Abstract 4181
Human clinical efficacy has been demonstrated with antisense oligonucleotides (ASOs) in several disease indications, including dyslipidemia, cancer, diabetes and multiple sclerosis. Second generation ASOs show potent pharmacology in many tissues, with liver being one of the most sensitive to ASO action. As the liver is responsible for production of many of the factors involved in blood coagulation we systematically designed and evaluated ASOs selective for several members of the coagulation cascade. ASOs targeting coagulation cascade members of both the intrinsic and extrinsic pathway produced highly specific target knockdown in liver. An overall aim of this study was to evaluate the contribution of the various factors to the coagulation process as well as to assess their relative risk/benefit relationships. The “risk” component was determined by bleeding tendency as measured by blood volume loss following tail nick, and the “benefit” component was determined by antithrombotic effect following ferric chloride induced thrombosis in the inferior vena cava. We have previously reported the activity of FVII and FXI ASOs in a ferric chloride mouse model without increased bleeding risk. Here we identify additional promising new antithrombotic targets. FII and FIX ASOs were able to reduce thrombosis, but inhibition of these targets had deleterious effects on the bleeding tendency. The ASO effects on PT and aPTT will be presented. The approach used in this study will be used to further characterize targets for antithrombotic potential and determine their ability to be combined with antiplatelet therapies. In addition to the characterization of antithrombotic targets, these ASOs will be evaluated and developed as potent, selective and potentially safer human antithrombotic therapeutics.

Disclosures:
Crosby: Isis Pharmaceuticals, Inc.: Employment. Gao:Isis Pharmaceuticals, Inc.: Employment. Zhao:Isis Pharmaceuticals, Inc.: Employment. Bhattacharjee:Isis Pharmaceuticals, Inc.: Employment. May:Isis Pharmaceuticals, Inc.: Employment. Zhang:Isis Pharmaceuticals, Inc.: Consultancy. MacLeod:Isis Pharmaceuticals: Employment. Monia:Isis Pharmaceuticals, Inc.: Employment.
Autologous Blood Donation for Apheresis of Peripheral Blood Hematopoietic Stem Cell in Low-Body Weight Children with Type 1 Diabetes.
Authors: LI CP , Zhou Rong-Fu , Zhou M. , Shao XY , Zhang QiGuo , Ouyang Jian 
Published: October 2019

Abstract
Abstract 4194

Backgroud
Autologous peripheral blood stem cells transplantation is widely used in treatment of malignant blood diseases, solid tumors and autoimmune diseases recently. Before apheresis, we filled the pipelines of Baxter CS-3000PLUS blood cell separator with the autologous blood instead of irradiated allogenetic blood.

Objective
The study is aimed to explore the safety and clinic efficacy of autologous blood donation for apheresis of stem cell in low body weight pediatric patients with type 1 diabetes.

Method:
There were three pediatric patients with type 1 diabetes in our hospital between August 2007 and December 2007. These patients included 2 male and 1 female with age of 5, 9, 9 respectively. Their weight was 15,18 and 23.5 kilograms respectively. Their blood test indexes were HB>120g/L,HCT>34%. On the 14th day before apheresis, 100ml autologous blood was collected and preserved in 4°C. Mobilization program was CTX 2g/m2 for 2 days and G-CSF 5∼10 μg/kg/d on the 5th day of before apheresis. Apheresis was initiated when WBC>5.0×109/L. SVSCH and SVCC were installed to blood cell separator at first. Before apheresis, we filled the pipelines of blood cell separator with the autologous blood instead of irradiated allogenetic blood.

Result
On the 9th day after the autologous blood donation, RBC ? AHB and HCT went back to the original level. In the process of apheresis.,every vital sign including blood pressure and heart rate was normal during apheresis. Hypotension or hyperthermia did not appear. The amount of CD34+ cell reached to 1.28-3.05×106/kg.

Conclusion
It is concluded that autologous blood donation is a safe and an effective method to avoid allogenetic blood transfusion for apheresis of stem cell in low body weight pediatric patients.

Disclosures:
No relevant conflicts of interest to declare.
Congenital Factor XIII Deficiency as Cause for Intracraneal Hemorrhage.
Authors: Dasi Maria Angeles , Argiles Bienvenida , Cid Ana R , Carreras M. Carmen , Aznar J. Antonio , Santos Maria Teresa , Valles Juana , Peinador Magdalena 
Published: October 2019

Abstract
Abstract 4208
Severe congenital factor XIII (FXIII) deficiency is an autosomal recessive disease of with a low prevalence in the general population (3-5 cases per million), associated with generally severe hemorrhagic diathesis, where the presence of intracraneal hemorrhage (ICH) is much higher than in other coagulopathologies such as hemophilia A or B. However, the basic coagulation tests are normal, which could delay the diagnosis.
We present three cases of severe congenital FXIII deficiency (not diagnosed when referred to our center) with severe hemorrhagic pathology. These patients had normal basic coagulation tests and did not have a family bleeding history. The table show the results.
Table Patient 1 Patient 2 Patient 3 Date of birth 1959 1978 2006 Sex Female Female Female Age at diagnosis 15 years old 12 years old 18 months old Cause of patient remission Ankle hemarthrosis Seizures Subdural hematoma Subdural hematoma Prior hemorrhagic history -umbilical cord bleeding-frontal hematoma requiring surgical management at 12 months-bleeding with dentition -umbilical cord bleeding-hematoma in buttock requiring RBC transfusion for anemia.-hemarthrosis in both knees -umbilical cord bleeding-growing cephalohematoma until 3rd week of life-hematoma by venipuncture lasting 2-3 weeks at 6 months.-delayed healing-Subdural hematoma after minor trauma 3 days prior. basic coagulation tests (PT, APTT, TT, fibrinogen) Normal Normal Normal Level of functional FXIII <1% < 5 % < 5 % Initial treatment Plasma Plasma FXIII concentrate Prophylaxis -Plasma: 2 Units every 6 weeks -FXIII concentrate every 4 weeks (since 1994) FXIII concentrate every 4 weeks FXIII concentrate every 3 weeks Evolution Major ICH at 30 years old. (had suspended prophylactic treatment in1989) Favorable evolution without consequences. Favorable evolution without consequences.

COMMENTS
Congenital Factor XIII deficiency, although infrequent, should be included in the differential diagnosis of hemorrhagic processes with normal coagulation tests, especially if triggered spontaneously or in a disproportionate manner (in quantity and/or duration). Bleeding of the umbilical cord in the first days or weeks after birth is characteristic of this deficiency (present in 80% of cases). The prophylactic administration of Factor XIII is fundamental due to the frequency of intracranial hemorrhaging.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Implications of Clonal Cytogenetic Abnormalities of Aquired Aplastic Anemia.
Authors: Kim Sung Hyun , Lee Ji Hyun , Kwon Kyung A. , Lee Suee , Oh Sung Yong , Kwon Hyuk-Chan , Han Jin-Yeong , Song Moo-Kon , Chung Joo-Seop , Lee Sang-Min , Joo Young-Don , Lee Ho Sup , Kim Yang Soo , Kim Hyo Jin 
Published: October 2019

Abstract
Abstract 4217

Background
Cytogenetic abnormalities (CA) have been reported infrequently in patients with otherwise typical aplastic anemia (AA). The relevance of CA in AA to the prognosis of AA and the evolution to the hematologic malignancies is controversial.

Design and Methods
One hundred and twenty-nine adult AA patients from four centers located in Busan, South Korea, who had successful cytogenetics at initial diagnosis were retrospectively analyzed.

Results
.The median follow-up duration of the overall patients was 46.8months. The ratio of severe AA to non-severe AA was 59:41. The patients were classified into 5 groups according to the CA and progression to the hematologic malignancies. Among the patients with normal cytogenetics at initial diagnosis, 117 remained AA with normal cytogenetics (Group 1). Six patients (4.7%) had CA at initial diagnosis (Group 2). The CA showed trisomy 8 in two cases and trisomy 11, deletion of Y chromosome, t(2;9), and t(22;?) in each case. One with trisomy 11 later developed monosomy 1. None of the Group 2 evolved to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Two patients with normal cytogenetics at initial diagnosis later developed monosomy 4, and monosomy 7, respectively, with persistent AA (Group 3). Group 3 patients were treated only with intermittent transfusion but spontaneously recovered from cytopenia and are still alive without transfusion requirement. Among the AA with normal cytogenetics at initial diagnosis, four patients (3.2%) progressed to AML or MDS; two remained normal cytogenetics (Group 4), and two patients obtained structural CA (Group 5) at follow-up, respectively.

Conclusion
The majority of the AA patients had normal cytogenetics at initial diagnosis. Non-severe AA patients may have CA. AA patients with CA at initial diagnosis or at follow-up are not at greater risk of evolution to the hematologic malignancies, and have no significant difference in survival. Prospective studies and more patients are needed to establish the clinical relevance of CA.

Disclosures:
No relevant conflicts of interest to declare.
Evaluation of Stem Cell Concentrate Prepared From Bone Marrow Aspirate Using the Res-QTM system.
Authors: Kumar Vijay , Chapman John R 
Published: October 2019

Abstract
Abstract 4232

BACKGROUND
The Res-Q System is a point of care device intended for the preparation of cell concentrates from bone marrow by centrifugation. Stem cell concentrates from bone marrow aspirate (BMA) were prepared in less than 15 minutes. The bone marrow concentrate was collected in the device funnel and extracted in a harvesting syringe. The cellular components of samples were analyzed pre- and post processing.

STUDY DESIGN
For this study 4 anticoagulated bone marrows were processed. All samples were evaluated for cell recovery, hematocrit, total nucleated cells (TNC), mononuclear cells (MNC), CD34+ cells, cell viability and colony forming units before and after Res-Q60 processing. The Res Q processed post samples were cultured and cells characterized by flow cytometry using cell surface markers.

RESULTS
The Res-Q60 process achieved MNC fraction volumes of 6.7 ± 0.1 ml with a final average hematocrit of 17± 0.6%. The post-processing recovery of CD34+ cells was 90 ±12.7%, of MNC was 85 ± 4% and of TNC was 64 ± 13%. No change in cell viability was observed using the Res-Q60 device. Res-Q derived cell concentrate cultured in mesenchymal stem cells basal media followed by immunophenotyping measured by flow cytometry were ≥ 95% positive for CD73, CD90 and CD105. The same cells lack (≤ 5%) expression of CD31 and CD34.

CONCLUSIONS
In conclusion, Res-Q60 system provides a new simple method for preparation of cell concentrates from bone marrow at the point of care.

Disclosures:
Kumar: Thermogenesis Corp.: Employment. Chapman:Thermogenesis Corp.: Employment.