bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Trial of a Portable Electrical Muscle Stimulator (VeinoPlus®) to Improve Symptoms of Postthrombotic Syndrome.
Authors: Soriano Catherine , Deal Allison , Boles Jeremiah C. , Moll Stephan 
Published: October 2019

Abstract
Abstract 4540

Background
Limited treatment options exist for postthrombotic syndrome (PTS). We performed a trial in patients with PTS of a portable electrical muscle stimulation device, VeinoPlus®, which delivers electrical impulses to leg muscles for 20 minute periods via 2 cutaneously placed electrode pads. Aims were to determine whether use of the device was a “clinical success” (defined by patient reporting improvement of symptoms, plus an interest and willingness to continue using the device) and improved quality of life (QOL) and severity of PTS findings; and to define optimal electrical intensity for greatest symptom relief.

Methods
Patients were told to use different voltages and numbers of treatment periods, and experiment with pad placement, to find intensity, frequency of use, and pad position for optimal PTS symptom relief. Assessments (Villalta score, QOL questionnaire) were obtained at study entry and after 8 weeks of device use.

Results
Twelve patients were enrolled: 3 had severe, 4 moderate, 5 mild PTS. To date, 8 patients have completed the study. Clinical success occurred in 5/8 (63%) of patients. 63% of patients had an improved VEINES questionnaire score on the symptom subscale, 75% on the QOL subscale. Villalta score on the most affected leg improved for 50% of patients. Most patients used the device in the intensity range of 25-35.

Conclusion
The VeinoPlus® electrical stimulation device appears to improve symptoms and QOL for patients with PTS. The study provides the rationale and details needed for a larger follow-up randomized, sham-device controlled, double-blind trial.

Disclosures:
No relevant conflicts of interest to declare.
Erythropoietin Treatment Leads to Reduced Blood Glucose Levels and Body Mass: Insights From Murine Models.
Authors: Katz Odelia , Stuible Matthew , Golishevski Nataliya , Lifshitz Lilach , Tremblay Michel , Gassman Max , Oster Howard S , Mittelman Moshe , Neumann Drorit 
Published: October 2019

Abstract
Abstract 4557
Erythropoietin (EPO) regulates proliferation and differentiation of erythroid precursor cells into erythrocytes. The last decade has revealed non-renal sites of EPO production and extrahematopoietic expression of the EPO-receptor (EPO-R), suggesting that EPO has pleiotropic functions. We have previously shown anti-cancer and immunomodulating effects of the hormone in humans and mice. Here we addressed the interplay among EPO, glucose metabolism, and body weight by employing a panel of relevant experimental murine models. The models focused on situations of increased EPO levels, including EPO-injected C57BL/6 and BALB/c mice, as well as transgenic mice (tg6) constitutively overexpressing human EPO and thus exposed to constantly high EPO serum levels. As experimental models for diabetes and obesity we employed protein Tyr phosphatase 1B (PTP1B) knockout mice associated with resistance to diabetes (PTP1B-/-), and ob/ob mice susceptible to diabetes and obesity. Our data demonstrated an EPO-associated decrease in blood glucose levels in all mice models tested. The tg6 mice, continuously exposed to EPO, were hypoglycemic even under non-fasting conditions. Blood glucose reduction in the experimental models tested was evident already one week following EPO administration in all models, including the PTP1B-/- and ob/ob mice. This conclusion gained further support by the glucose tolerence test (GTT). EPO overexpression or administration led to improved glucose clearance in all the tested murine models. Notably, in the ob/ob mice we observed EPO-associated attenuation of body weight gain and reduction of hemoglobin A1C. Preliminary clinical observations with several diabetic patients support these data and will be discussed further. Taken together our data bear significant clinical implications for EPO treatment in the management of a wide range of metabolic diseases and add an important novel therapeutic potential to this pleiotropic hormone.

Disclosures:
Mittelman: BioGAL- Start up (inactive): Equity Ownership, Patents & Royalties. Off Label Use: Non erythroid effects: immune, anti-cancer (all under investigation).
Upregulation of HLA-G Gene Expression in Malignant Hematopoietic Cells Treated with 5-Aza-2′- Ddeoxycytidine.
Authors: Alsabty Firas , Mistrik Martin , Polakova Katarina 
Published: October 2019

Abstract
Abstract 4567

Introduction
Human leukocyte antigen G (HLA-G) is a nonclassic HLA class I antigen with restricted distribution in normal tissues. It exerts multiple immunregulatory functions that have been suggested to contribute to the immune evasion of tumour cells. Ectopic HLA-G expression observed in some pathological conditions such as malignant transformation may be triggered by epigenetic modifications such as DNA demethylation or histone acetylation.

Materials and Methods
Mononuclear cells were isolated from peripheral blood of newly diagnosed previously untreated patients with acute myeloblastic leukemia (AML) (n=9) and chronic lymphocytic leukemia (CLL) (n=5) by standard Ficoll-Hypaque density gradient centrifugation. Isolated cells were resuspended in RPMI 1640 medium supplemented with 2mM L-glutamine, 200 μg/ml gentamicin, 0.125 μg/ml amphotericin B and 10% heat-inactivated fetal bovine serum. Demethylating treatment of cells was carried out with100 μM 5-aza-2x- deoxycytidine (AdC) (Sigma) for 3 days. Human choriocarcinoma cell lines JEG3 and JAR (ATCC, Rockville, MD) were used as HLA-G positive and negative controls, respectively. Real time polymerase chain reaction (RT-PCR) and semiquantitative RT-PCR were performed using the ABI Prism 7000 Sequence Detection System and AmpliTaq Gold DNA polymerase to detect HLA-G mRNAs transcriptions. The HLA-G protein expression was examined by western blot analysis using mAb 4H84.

Results
HLA-G transcripts in AdC untreated leukemia samples were demonstrated in 3 out of 5 patients (60%) with B-CLL and in 5 out of 9 patients (56%) with AML. Treatment with demethylating agent AdC resulted in up-regulation of HLA-G transcription and expression of HLA-G protein in 5 out of 8 (63%) examined leukemia cell lines (Table 1).

Conclusions
we conclude that DNA methylation is an important control mechanism of HLA-G gene expression, and treatment of human leukemia with demethylating agent AdC may up-regulate HLA-G gene expression and induce HLA-G protein synthesis in some patients that may allow leukemic cells to escape recognition and destruction by cytotoxic T-cells or NK cells. Therefore patients should be monitored for HLA-G expression in order to follow risk of AdC therapy.

Disclosures:
No relevant conflicts of interest to declare.
Mesenchymal Stem Cells From Patients with Acute Myeloid Leukemia (AML) Can Differentiate Into B-Cells in NOD/SCID/IL-2Rγ-/- Mice.
Authors: Wang Rui-Yu , Shi Yue-Xi , Zeng Zhihong , Schober Wendy D. , McQueen Teresa J. , Hopwood Vicki L. , Korchin Borys , Konopleva Marina , Andreeff Michael 
Published: October 2019

Abstract
Abstract 4573
Human mesenchymal stem cells (MSCs) derived from bone marrows are characterized by high proliferative potential and pluripotentiality to differentiate into multiple lineages such as osteo-, chondro-, and adipogenic cells. MSC express CD105, CD73 and CD90, but not CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. In this study, we observed that MSC derived from the bone marrow of four AML patients differentiated into B-cell lymphoblasts with NOD/SCID/IL-2Rg-/- engraftment potential.
MSC cell lines were established by culturing adherent cells from newly diagnosed AML (n=4) age 20 to 74 years in alpha-DMEM medium supplement with 20% fetal bovine serum. Surface antigen phenotype analysis and G-banding karyotype analysis were performed in passage 2 to 4. FACS-sorted CD90 positive cells were then intravenously (I.V.) injected into NOD/SCID/IL-2Rg-/- (NOG) mice via tail vein (n=9) or into the bone marrow (n=3). Circulating cells were analyzed for CD19, CD33, CD34, and CD90 expression on day 36, 45, 60, 75 after injection of MSC.

Results
1) G-banding showed normal karyotype in all MSC; 2) Injected MSC engrafted and differentiated in NOG mice. Surprisingly, CD19 positive cells were found in all samples starting on day 36 (table) and increased on day 60 and 75 (from d36: 6.9±3.5%, d45:0.7±0.1%, d60:2.6 ± 1.6% and d75: 9.3 ± 1.0%); 3) CD90 positive cells were found on day 45 (range from 0.07-3.96% and decreased to 0.1-0.5% on day 75). Low percentage of CD33 (day 45: 0.19-0.78% and day 60: 0.12-2.53%) and CD34 positive cells (day 45: 0.32-1.9% and day 60: 0.21-2.39%) were observed before day 60 and were undetectable by day 75.
Table shows the percentages of CD19+ cells found in circulation in NOD/SCID/IL-2Rg-/- (NOG) mice after MSC I.V. or intra-bone marrow injection. (* Mice died after phlebotomy.)

Conclusion
Human MSC derived from AML bone marrows have the capacity to differentiate into CD19 positive B lymphocyte in NOG mice in vivo. It has previously been reported that AML can be propagated by a leukemic stem cell with lymphoid characteristics (Cancer Cell 2006, 10, 363-74). Data reported here suggest the possibility that AML-derived MSC give rise to lymphoid cells that engraft in NOG mice. This unexpected finding could shed light on the role of stroma cells in the pathogenesis and propagation of leukemias.

Disclosures:
No relevant conflicts of interest to declare.
Homing and Engraftment of Bone Marrow Derived Cells in Irradiated Mouse Lungs.
Authors: Salimi Umar , Rajagopalan Malolan , Rwigema Jean-Claude , Dixon Tracy , Shen Hongmei , Epperly Michael W. , Stripp Barry , Greenberger Joel 
Published: October 2019

Abstract
Abstract 4600
To determine the degree to which murine bone marrow migrates to and can repopulate damaged lung, we studied lung stem cell expression of the Clara Cell Specific Protein (CCSP). Several different models have been used to deplete the lung stem cells. We used CCtk mice which expresses the HSV-tk under control of the CCSP promoter. Subcutaneous administration of gancicylovir (50 mg/ml) over a 7 day period using Alzet osmotic pumps results in the reduction of CCSP RNA and CCSP positive cells. To determine if a reduced dose of gancicylovir reduced CCSP cells to a nonfatal degree and opened a stem cell niche for homing of hematopoietic cells, CCtk mice had osmotic pumps placed subcutaneously containing a lower dose of 25 mg/ml of gancicylovir. The lungs were explanted at serial times up to 7 days after pump placement. RNA was extracted and real time polymerase chain reaction (RT-PCR) using primers specific for CCSP was used to quantitate CCSP expression. CCtk mice treated with gancicylovir showed a 70% reduction of lung CCSP expression. CCtk mice implanted with osmotic pumps containing 25 mg/ml gangcicylovir and injected intravenously with bone marrow from sex-mismatched GFP+ transgenic FVB male mouse 2 days later were followed for thirty days. The mice were sacrificed, lungs removed, single cell suspensions prepared, stained with a PE labeled anti-CD45 monoclonal antibody and analyzed by flow cytometry for GFP positive, CD45 negative cells. No GFP+, CCSP+ cells cells were detected. Injection of FVB mice with naphthalene (which kills differentiated but not stem CCSP+ cells) at 200 mg/kg intraperitoneally resulted in an 87% decrease in CCSP expression. When injected with bone marrow cells from GFP+ transgenic mice at serial times to 7 days and sacrificed at day 30, again no GFP+ CCSP+ cells were identified. In a third attempt to remove additional CCSP cells and prepare sites for homing of marrow cells, FVB mice were treated with naphthalene (200 mg/kg) followed by 20 Gy irradiation to the lungs 48 hr later, then injected with GFP+ bone marrow, 24 hr later. The mice were sacrificed 30 days later, and examined for GFP+, CD45- cells. Low numbers of GFP+ CCSP+ cells were detected. The data indicates a low baseline level of hematopoietic stem cell potential to home and differentiate to CCSP positive lung cells.
Supported by NIH-2R01CA119927-08A1.

Disclosures:
No relevant conflicts of interest to declare.
The Role of Periodic Limb Movement in Sleep of Patients with Sickle Cell Disease.
Authors: Roizenblatt Marina , Roizenblatt Suely S , Vicari Perla , Arruda Martha M A S , Chediek Felipe , Abrantes Fabiano , Morais Antonio V , Tufik Sergio , Figueiredo Maria Stella 
Published: October 2019

Abstract
Abstract 4609

Background
In last decade, there has been growing research in sleep disorders associated with sickle cell disease (SCD), particularly focusing on oxyhemoglobin desaturation. The coexistence of periodic limb movement (PLM) and anemia is well known, however it remains controversial to which extent dopamine deficiency, lower serum ferritin levels or iron deficiency contribute to the pathophysiology of PLM in anemia.

Objective
The aim of this study is to evaluate the relationship between PLM and other manifestations of SCD

Methods
Eight male patients with SCD were age and BMI-matched to 16 healthy controls (1:2) for sleep evaluation by clinical inventory and polysomnography (PSG). PLMS were defined as limbs movements lasting 0.5–5 seconds that recur every 5 to 90 seconds in a series of ≥ 4. Serum levels of ferritin and hemoglobin were assessed.

Results
Comparing to controls (aged 28.6 ±5.9 yrs, BMI of 22.1 ±3.8 kg/m2), SCD patients (aged 28.0 ±7.3 yrs, BMI of 21.4 ±4.6 kg/m2 p>0.05, both) scored their sleep satisfaction as moderate (75% vs. 12.5%, p=0.005), whereas 50% of controls scored it as very satisfactory (vs. none of the SCD patients, p=0.02). Awakenings in the middle of the night were frequently reported by SCD patients (87.5% vs. 43.7%, p= 0.05) as well as pain complaints (87.5% vs. 37.5%, p=0.03). PSG data revealed that, compared to controls, SCD patients exhibited decrease in sleep efficiency (76.7% ±12.6 vs. 87.9% ±4.8, p=0.004), in REM sleep percentage (10.6 % ±6.0 vs. 20.3% ±5.8, p=0.001), and increase in wake after sleep onset (65.3%±38.9 vs. 32.4% ±20.2, p=0.012), arousal index (16.3/hour ±8.5 vs. 9.5/hour ±4.9, p=0.021), PLM index (13.1 ±10.1 vs. 2.8 ±3.3, p= 0.001), apnea hypopnea index (8.8/hour ±5.6 vs. 3.4/hour ±5.0, p=0.025). Lower mean oxyhemoglobin saturation (88.0 mmHg ±3.4 vs. 92.4 mmHg ±5.4, p=0.049), and hemoglobin levels (8.7g/dl ±1.1 vs. 15.8g/dl ±0.7, p<0.001) were also verified in SCD patients. Interestingly, ferritin levels did not differ between groups (209.6±132.8 in SCD patients vs. 214.8 ±142.2, p=0.949). Linear regression showed that SCD condition represented an independent risk feature for PLM (R2 = 0.51, p<0.001). Correlation between PLM and the number of comorbities related to SCD was substantial (r=0.79, p=0.02)

Conclusions
Subjective sleep complaints reported by patiens with SCD were supported by PSG findings of sleep disruption and lower mean oxyhemoglobin saturation. Increase in PLM in SCD patients correlated the number of comorbities of the disease. In contrast with the literature, ferritin did not play a role in the pathophysiology of PLM in these patients.
This study was supported by FAPESP CEPID 98/14303-3 and AFIP

Disclosures:
No relevant conflicts of interest to declare.
Pregnancy as a Risk Factor for the Patients with Hodgkin Disease: Preliminary Report.
Authors: Grudeva Janet G. 
Published: October 2019

Abstract
Abstract 4636
Pregnancy as a risk factor for the patients with Hodgkin disease: preliminary report
Grudeva-Popova J1, Nenova I1, Spasova M2
1Department of Oncology and Hematology, 2Department of Pediatrics and Medical Genetic, University Hospital “St George” – Plovdiv, Bulgaria
Hodgkin disease is a potentially curable lymphoid malignancy, affecting predominantly young age. However, subsequent pregnancy in women in child-bearing age, previously diagnosed with Hodgkin disease, may raise some medical and ethical considerations regarding the prognosis of both mother and child. There are few published reports with controversial results about the influence of pregnancy on the duration of remission and overall survival of this subgroup of patients. The objective of the study is to analyze the long-term sequelae of subsequent pregnancy for women previously diagnosed with Hodgkin disease.

Patients and methods
We studied retrospectively 224 patients with Hodgkin disease, diagnosed, treated and followed-up during a 15-year period (1994-2009) at the Department of Hematology and the Department of Oncology and Hematology, University Hospital. Women in child-bearing age numbered 51, and pregnancy after the diagnosis of Hodgkin disease occurred in 5 of them. We analyzed the prognostic factors and possible influence of pregnancy on the duration of remission, and overall survival by logistic regression model and κaplan-Meier survival estimation.

Results
Relapse occurred in 3 out of 5 women with Hodgkin disease. Subsequent pregnancy with fatal outcome occurred in 2 of the 3 soon after delivery. We identified the following prognostically unfavorable factors in this subgroup of patients: advanced clinical stage, presence of B symptoms at the diagnosis of Hodgkin disease, lymphocyte depletion histology, and short time interval between the end of therapy and pregnancy. For the other 2 women pregnancy ended successfully for the mother and child, possibly because of a time interval exceeding 3 years between occurrence of remission and the pregnancy. Median survival time of the observed group was 73 months (95% CI: 10-137) and was shorter, compared to the survival time of the patients in the control group: 212 months (95%CI: 136-288).

Conclusion
The preliminary results of the study of this small subgroup of patients with Hodgkin disease show that women in child-bearing age previously diagnosed with Hodgkin disease, particularly with unfavorable prognosis, have increased relapse risk in case of subsequent pregnancy. The relapse risk appears to be higher in the first 3 years after remission induction.

Disclosures:
No relevant conflicts of interest to declare.
Optimal Post-Dose Levels of Cyclosporine A at a Higher Peak Concentration Are Correlated with the Area Under the Concentration-Time Curve of Twice-Daily Infusion and Oral Administration in Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Inoue Yasuyuki , Saito Tasuku , Ogawa Kohei , Nishio Yuji , Kosugi Seiju , Suzuki Yoshinori , Shibuya Yasushi , Kato Masayuki , Takahashi Masatomo , Miura Ikuo 
Published: October 2019

Abstract
Abstract 4656

Introduction
Cyclosporine A (CyA), a calcineurin inhibitor, is widely used as an immunosuppressor for the prevention of acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal regimen of CyA has not yet been unequivocally established. Among liver transplant patients, it is important to maintain a peak CyA concentration and to monitor area under the concentration-time curve (AUC) and 2 h after CyA dosing (C2) for prophylaxis against graft rejection. We investigated the pharmacokinetics of CyA delivered by twice-daily infusion and oral administration maintained with a peak level above 1000 ng/ml to keep AUC 0-24 higher than 10000 ng-h/ml in 10 patients with hematological malignancy who underwent alloHSCT.

Methods
CyA was started as a twice-daily infusion at 1.5 mg/kg and then orally administered at twice the infusion dose in order to maintain the trough blood concentration between 200 and 500 ng/ml and with a peak level above 1000 ng/ml. Serial blood samples were collected at 0, 1, 2, 3, 5, 8, and 12 h after CyA dosing (C0,C1,C2,C3,C5,C8,C12) on days 14-21 after transplantation and on days 7-14 after switching to oral administration, and the AUC was calculated.

Results
The mean AUC0-12 for twice-daily infusion and oral administration was 7443±998.5 ng-h/ml and 7185±1714 ng-h/ml, respectively. Among all the patients, the AUC0-24 for both CyA twice-daily infusion and oral administration was higher than 10000 ng-h/ml. Two close relationships were observed between AUC0-12 and the C3 level for infusion and between AUC0-12 and the C8 level for oral administration. Engraftment was achieved in all cases, and two patients suffered from grade 2 aGVHD. None of the patients had grades 3-4 aGVHD or other serious complications.

Conclusion
This strategy was well tolerated, and the C3 level for twice-daily infusion and the C8 level for oral administration were the optimal points for monitoring of CyA concentration in the early phase of alloHSCT.

Disclosures:
No relevant conflicts of interest to declare.
Lymphoproliferative Response to Herpes Simplex Virus, Cytomegalovirus, Epstein-Barr Virus, Varicella Zoster Virus, Human Herpes Virus 6, 7 and 8 Antigen Stimulation in Pediatric Allogeneic Stem Cell Transplant Recipients.
Authors: Cheng Frankie Wai Tsoi , Chan Paul Kay Sheung , Leung Wing Kwan , Lee Vincent , Shing Matthew MK , Li Chi Kong , Leung Ting Fan 
Published: October 2019

Abstract
Abstract 4663

Introduction
Delayed immune reconstitution is a major cause of transplant-related mortality in allogeneic stem cell transplant setting. Reactivation of herpes viruses is a common post-transplant complication. In this study, we evaluate the recovery of cell-mediated immunity (CMI) to various herpes viruses by measuring lymphoproliferative response (LPR) to specific recall antigens.

Materials and Methods
Cell-mediated immunity was evaluated by the in-vitro lymphoproliferative response of peripheral blood mononuclear cells (PBMC) to specific purified HSV, VZV, CMV, EBV, HHV-6, 7, 8 antigens. Results were expressed as stimulation index (SI). SI≥a3 was regarded as positive lymphoproliferative response (LPR). Serial measurements were made at before transplant, and monthly during the initial 6 months post-transplant then quarterly till 12 months post-transplant.

Results
From 2001-2004, 36 patients (M=19; F=17) with median age 10.5 years old were recruited. Hematological malignancies accounted for 58.3% of cases. Most transplants were from matched siblings (MSD) with peripheral blood stem cells (PBSC) as the source of stem cells. Altogether 50% of subjects showed positive LPR to HSV, CMV and VZV antigens at 2-4 months post-transplant; A significant upsurge of LPR were observed at 4-6 months post-transplant. However, no positive LPR to HSV, HHV-6,7 and 8 antigens were observed. The antibody status of donor and recipient for HSV, CMV and VZV were associated with the timing of recovery of CMI. Donor choice and stem cell source were important determinants of eventual LPR at day 100 post-transplant.

Conclusion
More than half of transplant recipients developed satisfactory LPR to HSV, CMV and VZV at 2-4 months after transplant. Pre-transplant serostatus of donor and recipient, donor choice and stem cell are important determinants of LPR to herpes viruses.

Disclosures:
No relevant conflicts of interest to declare.