bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring Quality of End-of-Life Care for Blood Cancers: A National Survey of Hematologic Oncologists
Authors: Odejide Oreofe O. , Cronin Angel M. , Condron Nolan B. , Fletcher Sean A. , Earle Craig , Abel Gregory A. 
Published: October 2019

Abstract
Background: Hematologic malignancies have been associated with poor performance on standard measures of quality of end-of-life (EOL) care in oncology (eg, Hui, Cancer, 2014); however, these measures were originally developed primarily for solid tumors, and they may not appropriately address EOL quality issues for patients with blood cancers. We sought to explore hematologic oncologists' perspectives regarding the acceptability of current oncology EOL quality measures, hypothesizing that they would report them to be largely unacceptable.
Methods: In 2014, we mailed a 30-item survey to a national sample of hematologic oncologists randomly selected from the American Society of Hematology clinical directory. The survey was developed through focus groups (n=20) and cognitive debriefing (n=5) with hematologists whose practices focus on patients with blood cancers. In the resulting survey, we provided a list of standard EOL quality measures (Earle, JCO, 2003; Keating, Cancer, 2010; Phelps, JAMA, 2009; see table) and two novel hematology-based measures (no red cell transfusions ≤ 7 days before death, and no platelet transfusions ≤ 7 days before death) and asked "Please indicate whether or not you feel each is an acceptable indicator of good quality EOL care for patients with hematologic malignancies." We decided a priori that we would consider a measure to be "highly acceptable" if there were at least 75% agreement among hematologic oncologists on its acceptability. Worrying that they might reject them all, we also asked them to identify three measures they would choose in a scenario where three had to be adopted.
Results: We received 349 surveys from 48 states (response rate: 57.3%). Non-responders were not significantly different across known variables (gender and region of practice). Among respondents, median age was 52 years, median time in practice was 25 years, and 43% practiced primarily in tertiary centers. Eighty-seven percent were board-certified in oncology, 81% in hematology, and 71% in both specialties. The table below shows acceptability of the quality measures as rated by respondents.
In the exercise where three measures had to be chosen, the one chosen most often was no CPR within 30 days of death (54%), followed by enrollment in hospice >7 days before death (46%).
Conclusions: In contrast to our hypothesis, all of the measures we presented were considered acceptable by a substantial proportion of the hematologic oncologists in our national cohort. Moreover, while four of the measures reached our a priori designation of being highly acceptable, the two hematology-focused measures did not meet this same threshold. These data suggest that in hematologic oncology, resources should be directed towards addressing barriers to performance on established EOL quality measures in addition to creating new ones.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Fertility Preservation for Women with Sickle Cell Disease (SCD)
Authors: Plowden Torie C , Millan Nicole M , Owen Carter M , Healy Mae W , Banks Nicole K , Hsieh Matthew , Fitzhugh Courtney D. , Witmyer Jeannine , Peak Doug , Frankfurter David , DeCherney Alan H , Tisdale John F , Wolff Erin F 
Published: October 2019

Abstract
Objective: Peripheral blood stem cell transplant (PBSCT) can now cure SCD in adults, but may result in a loss of future fertility. Little is documented regarding fertility preservation in women with SCD. The aim of this study was to perform fertility preservation for women with SCD scheduled for PBSCT.
Design: Prospective cohort of women with SCD undergoing fertility preservation prior to PBSCT at a large research hospital.
Materials and Methods: Patients underwent standard controlled ovarian hyperstimulation (COH) using an antagonist protocol cycle with leuprolide trigger under close multidisciplinary (including reproductive endocrinologists and hematologists) monitoring. All patients were continued on therapeutic or started on prophylactic anticoagulation prior to beginning COH, and maintained on hydroxyurea.
Results: Nine reproductive aged women were screened; 1 declined participation, 1 was diagnosed with unrecognized premature ovarian insufficiency, 1 had her fertility preservation cycle canceled due to poor response to fertility medications and 2 patients are scheduled for upcoming cycles. The remaining four women (ages 20, 34, 24, 27) successfully underwent COH, transvaginal oocyte retrieval and cryopreservation of mature eggs (n= 8, 13, 15, 21 oocytes, respectively). The third patient underwent two cycles due to low mature oocyte yield from her initial cycle. Headaches were reported by patients 1 and 2 following gonadotropin injections, with a negative neurologic workup including MRI in patient 2. Patient 3 underwent an exchange transfusion on day 10 of stimulation, which did not adversely impact serum reproductive hormone levels. Patients 3 and 4 reported an acute exacerbation of their chronic pain during COH, which responded well to intravenous fluids, IV and oral pain medications. Therefore, despite severe SCD and co-morbid conditions, the side effects were manageable. There were no venous thrombotic events.
Conclusion: These results provide support that fertility preservation can be safely performed in women with SCD under the care of a multidisciplinary team. The safest stimulation protocol (i.e. antagonist cycle with leuprolide trigger for final oocyte maturation) was successful in all patients despite multiple risk factors for failed leuprolide trigger. Fertility preservation is important not only before PBSCT to cure their underlying disease, but also because of high rates of premature ovarian insufficiency in the SCD population post-transplant.
Support: Intramural NICHD and NHLBI, NIH.

Disclosures
No relevant conflicts of interest to declare.
CD44 and PSGL-1 Collaborate in Controlling the Migration of Human Activated T-Cells
Authors: Ali Amal J. , Merzaban Jasmeen S. , Abuelela Ayman F. 
Published: October 2019

Abstract
Selectins play a central role in the trafficking of activated T cells by mediating tethering and rolling on vascular endothelium, acting as a beacon to help navigate them to the site of infection. Here we present a comprehensive binding and in vitro functional analysis of E-selectin ligands expressed on human activated T cells. Using a mass-spectrometric approach we identified a number of glycoproteins that may act as physiological E-selectin ligands on human activated T cells and focused on comparing the role the previously identified well-known E-selectin ligands, PSGL-1 (P-selectin glycoprotein ligand 1) to the newly identified ligand CD44. We show that CD44 from human activated CD4+ and CD8+ T cells binds E-selectin, and that immobilized CD44 mediates tethering and rolling of E-selectin expressing CHO cells via sialylated N-linked glycans. By knocking down CD44 and/or PSGL-1 in primary human activated T cells, our data demonstrate for the first time that CD44 is essential for mediating the rolling over E-selectin and thereby cooperates with PSGL-1 as a major E-selectin ligand on human activated T cells. This has major implications in the development of targeted therapies to combat inflammatory diseases and in transplantation settings.

Disclosures
No relevant conflicts of interest to declare.
Species-Specific Roles for a2,3- and a2,6-Linked Sialic Acid Residues in PECAM-1-Mediated Homophilic Interactions
Authors: Lertkiatmongkol Panida , Paddock Cathy , Newman Peter J. 
Published: October 2019

Abstract
PECAM-1 is a 130 kDa type 1 transmembrane glycoprotein belonging to the immunoglobulin gene (Ig) superfamily, and is constitutively expressed on the surface of circulating blood cells and endothelial cells. In platelets, PECAM-1 serves as an inhibitory receptor to limit thrombus growth, while on endothelial cells, PECAM-1 is a major junctional protein that functions to sense flow, mediate leukocyte transendothelial migration, and regulate vascular permeability. Previous studies have shown that PECAM-1/PECAM-1 homophilic interactions, mediated by amino-terminal Ig-homology domain 1 (IgD1), are required for its functions on endothelial cells. Interestingly, PECAM-1 is a heavily glycosylated receptor, with two of its nine N -linked glycans present in IgD1. Murine PECAM-1 is modified by addition of α2,6-linked sialic acid residues, and studies performed using recombinant murine PECAM-1 protein have shown that PECAM-1/PECAM-1 homophilic interactions are abrogated upon removal of sialic acid, and inhibited by α2,6- sialylated oligosaccharides, suggesting that these glycans may be important in PECAM-1 homophilic binding. Murine PECAM-1, however, does not bind human PECAM-1. A chimeric protein comprised of the human PECAM-1 extracellular domain fused with human Fc (PECAM-1/IgG) produced by Chinese Hamster Ovary (CHO) cells, which are able to add only α2,3-linked sialic acid residues, has been successfully used to study PECAM-1-mediated adhesive interactions for many years. Taken together, these data suggest that the mechanisms by which PECAM-1 interacts with itself may differ between species. The purpose of the present investigation, therefore, was to examine the role of glycans, specifically terminal sialic acid residues, in human PECAM-1 homophilic interactions. To determine whether the specific linkage of sialic acid affects human PECAM-1 homophilic interactions, we examined the relative ability of α2,3-sialylated PECAM-1/IgG - produced in wild-type CHO cells which lack α2,6-sialyltransferase activity - and α2,6-sialylated PECAM-1/IgG - produced in CHO cells that had been stably transfected with ST6Gal-1, to bind to PECAM-1-transfected REN cells. We found that α2,3-sialylated PECAM-1/IgG bound more than twice as well as α2,6-sialylated PECAM-1/IgG (mean fluorescence intensity (MFI) of 457,250 ± 33,049 versus 280,333 ± 78,589; normal human IgG bound with an MFI of 158,550 ± 62,133). These findings were further supported by molecular docking studies, which showed a preferential orientation for interactions between α2,3-linked sialic acid and amino acid K89 within PECAM-1 Ig homology domain 1 - a residue known to be important in PECAM-1 homophilic interactions. Taken together, these data provide important new conceptual information that improves our understanding of the role of glycosylation in PECAM-1 homophilic adhesive interactions.

Disclosures
No relevant conflicts of interest to declare.
Heart Failure Related Hospitalizations Are Associated with Increased Morbidity and Mortality in Pediatric Oncology Patients
Authors: Keeshan Britton , Lin Kimberly Y , O'Connor Matthew J , Ginsberg Jill P , Aplenc Richard , Shaddy Robert , Rossano Joseph 
Published: October 2019

Abstract
Introduction: Cardiomyopathy is a well-described complication of cancer therapy in pediatric patients. However, the prevalence and outcomes of heart failure related hospitalizations in these patients are unknown. We hypothesize that while heart failure related hospitalizations are uncommon in pediatric oncology patients, they are likely associated with increased morbidity and mortality.
Methods: We performed retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database, a nationwide database of pediatric hospitalizations in the United States, for oncology patients with and without heart failure for years 2000, 2003, 2006, and 2009.
Results: Heart failure was identified in 914 of 259,432 (0.4%) pediatric oncology admissions. Patients with heart failure were more likely to be non-white (52.2 vs 43%, p<0.001), less likely to be in the highest income bracket (23.9 vs 27.5%, p=0.014), more likely to have leukemia (40.7 vs 31.3%, p<0.001), and more likely to undergo bone marrow transplantation on admission (5.0 vs 1.6%, p<0.001). Several morbidities were significantly more common in patients with heart failure including respiratory failure [16.4% vs 1.3%, odds ratio (OR) 14.6, 95% CI 12.2-17.4), sepsis (21.9% vs 7.2%, OR 3.6, 95% CI 3.1-4.3), stroke (1.5% vs 0.6%, OR 2.5, 95% CI 1.5-4.3), and renal failure (11.7% vs 1.2%, OR 10.9, 95% CI 8.9-13.3). Length of stay (LOS) and hospital charges were also significantly greater in oncology patients with heart failure patients compared to those without; median LOS 9 (IQR 4-25) vs 4 days (IQR 2-6); median hospital charges $58,023 (IQR 18,835-169,826) vs $18,161 (IQR 8,860-39,640); p<0.001 for both. Hospital mortality was significantly greater in oncology patients with heart failure compared to those without (13.3% vs 1.3%; OR 11.5, 95% CI 9.5-14.0). On multivariable analysis, heart failure was independently associated with hospital mortality in pediatric oncology patients (OR 2.21, 95% CI 1.63-3.00).
Conclusion: Heart failure is an uncommon but serious complication in hospitalized pediatric oncology patients. The presence of heart failure was associated with increased morbidities, resource utilization, and mortality. Further study is needed for the prevention and treatment of heart failure in this population.

Disclosures
Aplenc: Sigma Tau: Honoraria.
Isolation and Characterization of Mesenchymal Stromal Cells Derived from Paediatric Patients with B Acute Lymphoblastic Leukemia
Authors: Dander Erica , Palmi Chiara , Portale Federica , Beneforti Linda , Biondi Andrea , Cazzaniga Giovanni , D'Amico Giovanna 
Published: October 2019

Abstract
PURPOSE: Several studies reported the importance of tumor microenvironment in the development and progression of hematological disorders. The identification of key factors involved in the crosstalk between the malignant cells and the bone marrow Mesenchymal Stromal Cells (BM-MSCs) may provide a tool for interfering with the protective BM niche. The purpose of our work was to isolate and characterize morphologically, phenotypically and functionally MSCs derived from pediatric patients with B Acute Lymphoblastic Leukemia (B-ALL).
METHODS: MSCs were isolated from BM-MNCs obtained from 10 B-ALL children (n=5 non-traslocated high risk patients and n=5 t(12;21) patients) and from 6 healthy donors (HDs) and cultured in DMEM 10% FCS. MSCs were characterized at fourth passage in terms of morphology, immunophenotype (FACS analysis) and in vitro adipogenic and osteogenic differentiation potential. Chromosomal translocations detected in leukemia cells were investigated in B-ALL-MSCs by fluorescence in situ hybridizations (FISH) or polymerase chain reaction (PCR).
RESULTS: Both HD-MSCs and B-ALL-MSCs resulted comparable in terms of morphology. They both expressed the typical MSC markers CD73, CD90 and CD105, while lacked the expression of the hematopoietic markers CD14, CD34, CD45 and MHC-II. HD-MSCs as well as B-ALL-MSCs were able to differentiate, under appropriate stimuli, into adipogenic and osteogenic lineages as showed by Oil Red O liphophilic dye and Alizarin Red staining of calcium deposits. In addition, MSC from all investigated ALL patients did not present the chromosomal translocations that had been detected in leukemia cells (1 patient BCR-ABL p210, 5 patients TEL-AML1).
CONCLUSIONS: We found that B-ALL-MSCs resulted similar in terms of morphology, phenotype and differentiation ability to HD-MSCs. Furthermore, MSCs from patients did not reveal the chromosomal translocations present in leukemia blasts. Functional characterization of MSCs in terms of soluble molecule production is needed to identify altered cellular pathways.
Since emerging evidence supports the importance of the MSCs in the leukemic niche, we will focus on the potential functional alterations of ALL-MSCs. Our purpose is to understand the mechanisms underlying the support of leukemic cells by the BM microenvironment. The discovery of altered molecular pathways will pave the way for the development of new immunotherapy strategies for targeting the leukemic niche.

Disclosures
No relevant conflicts of interest to declare.
The Expression and Effect of B7-H3 in Mantle Cell Lymphoma
Authors: Wang Jing , Zhang Wei , Wang Yanfang , Dong Fei , Zhu Mingxia , Wan Wenli , Li Haisheng , Wu Feifei , Yan Xinxing , Yang Xiao-Feng , Ke Xiaoyan 
Published: October 2019

Abstract

Objective : To investigate the effects of B7-H3 (CD276) on oncogenesis and chemosensitivity in mantle cell lymphoma (MCL).
Methods : The B7-H3 expression was detected by flow cytometry in cell lines, 20 patients with MCL and 20 volunteers. B7-H3 knockdown was performed using lentivirus transduction in the Maver and Z138 mantle cell lymphoma cell lines, respectively. The effects of B7-H3 on cell proliferation, cycle, migration and invasion were investigated by CCK-8 assay, methyl cellulose colony forming assay, PI staining, and Transwell assays in vitro. By establishing Maver and Z138 xenograft models, the effects of B7-H3 on tumourigenicity were observed, and Ki-67 and PCNA was detected through immunohistochemical. Moreover, the impacts of B7-H3 RNAi on the anti-tumor effect of chemotherapy drugs were determined with CCK-8, Annexin V-FITC/PI and Hoechst 33342 staining assays in vitro and with xenograft models in vivo.
Results: The frequency of B7-H3positive expression cases was 65.0% (13/20) in MCL patients and 10.0% (2/20) in volunteers. The down-regulation of B7-H3 significantly decreased tumor proliferation in MCL in vitro and in vivo. In the B7-H3 knockdown groups of Maver and Z138 xenograft models, the mean inhibition rate of tumor growth was 59.1% and 65.0% (p = 0.010 and 0.003), and the expression of both Ki-67 and PCNA were significantly lower, respectively. After B7-H3 silencing, the cell cycles of Maver and Z138 were both arrested at G0/G1 phase, and the expression of cell cycle-related proteins Cyclin D1 and CDK4 was lower. The cell migration rates and invasion capacity were decreased, and the rates of distant metastasis in B7-H3 knockdown both Maver and Z138 xenografts were significantly declined as well. The expression of invasion-related proteins MMP-2 and MMP-9 was lower in B7-H3 knockdown cells and xenografts. The silencing of B7-H3 increased the sensitivity of Maver and Z138 cells to Rituximab and Bendamustine and enhanced the drug-induced apoptosis, respectively. The activity of caspase-3 in vitro and the expression of caspase-3 in both Maver and Z138 xenografts was significantly increased in the B7-H3 shRNA combined with chemotherapy drugs groups.
Conclusions: B7-H3 levels in MCL patients were signifiantly higher than that in volunteers. Our study demonstrates for the first time that B7-H3 promotes mantle cell lymphoma progression and B7-H3 knockdown significantly enhances the chemosensitivity. This may provide a new therapeutic approach to mantle cell lymphoma.

Disclosures
No relevant conflicts of interest to declare.
Dynamic Variation and Clinical Significance of the Cytokine Level Changes in Children with Acute Leukemia during Chemotherapy
Authors: Wu Xuedong , Jing Yuanfang , Wen Jianyun , Chen Libai , Li Chunfu 
Published: October 2019

Abstract
Background:
Cytokines and infection are closely related. One of the hot spots is the indexes which can early diagnose and predict prognosis of febrile neutropenia patients with acute leukemia. It is importment to find predictors of infection in febrile neutropenia patients.
Aim:
To investigate the variation of CRP(C-reactive protein), IL-6(interleukin 6), IL-8(interleukin 8) and IFN-γ (interferon γ) in children with acute leukemia before and after febrile neutropenia, and evaluate the reliability of plasma interleukin (IL) and CRP levels as indicators of febrile neutropenia patient.
Methods:
We selected 40 cases of children with acute leukemia from Pediatric department of Nanfang Hospital,Southern Medical University,including 27 cases of acute lymphoblastic leukemia(67.5%),13 cases of acute myeloid leukemia(32.5%). The mean age was 7 years(range:1-14).We used Luminex immunoassay to detected levels of cytokines, which include CRP, IL-6, IL -8 and IFN-γ. Serum samples were collected before chemotherapy(T0),3 days after chemotherapy(T1), 1 day after confirmation of febrile neutropenia, (T2), 3 days after febrile neutropenia (T3), 7 days after febrile neutropenia (i.e. the use of antibiotics 7 days,T4), recovery after chemotherapy(T5).
Results: Compared T1、T5 to T0, the levels of CRP, IL-6 were no statistically significant(P>0.05). Compared T1 to T0, the levels of IFN-γ and IL -8 were statistically significant(P=0.005 and P=0.002); Compared T5 to T0 and T5 to T1, the levels of IFN-γ and IL-8 were no statistically significant(P>0.05). In T0, T1 and T5 phase, the levels of IL-6, IL-8, IFN-γ and CRP were not correlated (P>0.05). Compared T2, T3 to T0, the level of CRP increased significantly after infection early in the fever, and the level of CRP increased in 24 hours.Compared T2, T3 to T0, the levels of IL-6, IL-8 were statistically significant, the level of IL-8 decreased after infection, but the level of IL-6 level increased in 24 hours.There were significant positive correlation between CRP and IL-6 in T2, T3 and T4 phase.
Conclusions.
The level of CRP increased significantly after infection early in the fever, and the level of CRP increased in 24 hours. the level of IL-8 decreased after infection,but the level of IL-6 level increased in 24 hours.The levels of CRP, IL-8 and IL-6 can be useful markers to identify febrile neutropenia in children with acute leukemia.

Disclosures
No relevant conflicts of interest to declare.
Low Incidence of V617FJAK2 Mutation in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: Balatzenko Gueorgui , Spassov Branimir , Georgieva Yanica , Hrischev Vasil , Guenova Margarita 
Published: October 2019

Abstract
Background: V617F JAK2 mutation is a typical molecular finding in BCR-ABL-negative myeloproliferative neoplasms (MPN). The same abnormality has also been reported in other myeloid malignancies. However, the data regarding the incidence and clinical relevance of V617F JAK2 in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are conflicting.
Aim: To establish the incidence and clinical significance of V617F JAK2 mutation in AML and MDS patients in our institution.
Materials and Methods : AML and MDS patients with isolated bone marrow mononuclear cells were included in this study, as follows: (i) 139 AML patients (71 females; 68 males; mean age of 57.5±15.3 years), including: 122 - de novo AML, 7 - therapy related AML (t-AML) and 10 - secondary AML (sAML) after primary MPN [3 V617F JAK2(+), 2 V617F JAK2(-) and 5 with unknown initial V617F JAK2 status]; (ii) 35 MDS patients. V617F JAK2 mutation status was determined using allele-specific polymerase chain reaction (PCR) and PCR RFLP (Restriction Fragment Lenght Polymorphism) analysis.
Results: V617F JAK2 mutation was detected in 3 AML patients: (i) in 1/122 (0.8%) de novo AML patients - male patient with minimally differentiated AML, with no antecedent MPN and the leukemic population showed aberrant myeloid phenotype with co-expression of CD7 and overexpression of EVI1 gene, (ii) in 2/10 (20.0%) patients with sAML after MPN and both patients had V617F JAK2(+) sAML after V617F JAK2(+) primary myelofibrosis. Interestingly; in the same group, a female patient with V617F JAK2(+) essential thrombocythemia developed 5 years later V617F JAK2(-) sAML with an aberrant myelomonocytic phenotype and co-expression of CD56. None of the patients with t-AML or MDS tested positive for V617F JAK2.
Conclusion: V617F JAK2 mutation is a rare finding in AML and MDS patients. Higher incidence was observed in sAML after MPN. However, the mutation status at the AML stage may not be identical as that detected during the primary MPN.

Disclosures
No relevant conflicts of interest to declare.