bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Impact of Response with Bortezomib Induction on Myeloma Patients Receiving Autologous Stem Cell Transplantation.
Authors: Min Chang-Ki , Eom Hyeon Seok , Cho Byung Sik , Kim Yoo-Jin , Kim Hee-Je , Lee Seok , Cho Seok-Goo , Kim Dong-Wook , Lee Jong Wook , Min Woo-Sung , Park Chong-Won 
Published: October 2019

Abstract
Abstract 4590
Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) aged less than 65 years. Before the era of novel agents the absence of initial response to induction therapy had no impact on outcome after ASCT. With the introduction of novel agents response rate with initial therapy are now between 70% and 100%. This study analyzes the association of progression-free survival (PFS) and overall survival (OS) after ASCT with the response to induction therapy with a regimen that contains bortezomib for patients with MM.
We performed a retrospective analysis of 61 patients with MM who consecutively received bortezomib-containing regimens from 2 institutes before collection of peripheral blood stem cells and ASCT. The median age was 54 (34-65) years and 41 (67.2%) were male. Eight (16.4%) patients received bortezomib as a first-line therapy whereas the others as the second line or more. Melphalan alone was used for conditioning and 29 (47.5%) received thalidomide maintenance therapy.
Fifty four of 61 patients (88.5%) achieved objective response after bortezomib induction treatment. Post-bortezomib complete response (CR), very good partial response (VGPR) and partial response (PR) were present in 33 (54.1%), 6 (9.8%) and 15 (24.6%), respectively. After ASCT CR, VGPR and PR were 41 (67.2%), 3 (4.9%) and 6 (9.8%), respectively. Achieving CR, VGPR or PR after bortezomib therapy failed to show an improvement in PFS and OS after ASCT. In contrast, post-transplant responses markedly influenced the outcomes after ASCT; patients achieving either CR or ≥VGPR had significantly longer PFS (P=.001 and .035, respectively) and OS (P=.002 and .002, respectively) compared to those without CR or ≥VGPR. Post-transplant maintenance treatment was not associated with improved PFS and OS in this cohort.
Our data suggest that the response to bortezomib induction therapy could not predict outcome after ASCT. Achieving post-transplant CR or ≥VGPR is critical for prolongation of PFS and OS.

Disclosures:
No relevant conflicts of interest to declare.
Comparasion of Hyper-CVAD Chemotherapy with Autologous Stem Cell Transplantation In Patients with Peripheral T Cell Lymphomas: A Single Centre Report.
Authors: Xu Yang , Wu Xiaojin , Wang Ying , He Guangsheng , Sun Aining , Qiu Huiying , Tang Xiaowen , Fu Chengcheng , Han Yue , Jin Zhengming , Miao Miao , Depei Wu 
Published: October 2019

Abstract
Abstract 4601
Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis. To determine the role of Hyper-CVAD chemotherapy and autologous stem cell transplantation (ASCT) in PTCL, we retrospectively analyzed the outcomes of 31 patients with PTCL between 1999 and 2009. 15 patients received Hyper-CVAD chemotherapy with 3-year overall survival (OS) of 52.4% and 3-year progression free survival (PFS) of 25.7%. 16 patients received ASCT with 3-year OS of 76.2% and 3-year PFS of 61.3%. There was significant difference in 3-year PFS between the two treatments (P=0.012). Additionally, patients underwent ASCT with elevated LDH, ≥ 2 IPI points and extranodal involvement had a favorable outcome comparing with the ones received Hyper-CVAD chemotherapy. These findings might suggest that ASCT likely offer a durable survival benefit for patients with aggressive peripheral T cell lymphoma.

Disclosures:
No relevant conflicts of interest to declare.
Are Communication Tools Effective in Increasing Reporting Rate of Acute Hemolytic Reactions (AHR) In ITP Patients Treated with Rh (D) Immune Globulin?
Authors: Guirgis Faiz , Muller Carmen , Little Gregg , Sinclair Chris , Genereux Maurice 
Published: October 2019

Abstract
Abstract 4677

BACKGROUND:
Acute Hemolytic Reactions (AHR) associated with administration of Rh(D) Immune Globulin (WinRho® SDF, Cangene Corporation, Winnipeg, MB, Canada) have been infrequently reported during the last 15 years. AHR's as defined were any case reporting hemoglobin decrease, haptoglobin decrease, elevation of bilirubin occurring within hours to number ofdays after WinRho® SDF treatment irrespective of the degree of change from baseline. AHR's where plasma or urinary hemoglobin were positive were categorized as cases of Intravascular Hemolysis (IVH).

AIMS/PURPOSE:
To determine if communication tools such as publication of Case series (Gaines), Dear Doctor Letters and label changes stimulated reporting of AHR's and IVH.

METHODS:
Cangene's WinRho® SDF safety database from USA. was reviewed and analysed for the period 1995–2009. The reporting rate of AHR and IVH were calculated based on cases submitted by year and estimates of number of doses distributed in USA for ITP. These rates were trended to determine if the communication of safety risk was effective in stimulating reporting and decreasing rates of AHR or IVH cases.

RESULTS:
Gaines published 15 cases of IVH after WinRho® SDF in April 2000. Label changes and Dear Healthcare Professional (DHCP) letters were issued in 2000. Gaines reported 6 cases of disseminated intravascular coagulation with IVH in September 2005 and label was changed with Dear Healthcare Professional letters issued in Dec 2005. Reporting rate of IVH was not affected by these warnings. Increase in reporting rate of AHR's was seen after publications and warning letters in 2000 and 2005.

CONCLUSION:
The overall reporting rate of AHR (including IVH) was estimated as infrequent (0.12%) while IVH reporting frequency was rare (0.03%).
Despite significant communication through FDA publications, medical education efforts and DHCP letters, there has been no appreciable change in reporting frequency of hemolytic events following Rh (D) Immune Globulin administration. This suggests that the initial estimate of IVH occurring at approximately 1:1000 doses (Gaines 2000) is still appropriate.

Disclosures:
Guirgis: Cangene Corporation: Employment. Muller:Cangene Corporation: Employment. Little:Cangene Corporation: Employment. Sinclair:Cangene Corporation: Employment. Genereux:Cangene Corporation: Employment.
Design and Construction of Multi-Epitope Fusion Gene Vaccine of Wilm Tumor Gene WT1 and Stimulating Epitope of Mycobacterium Tuberculosis Heat Shock Protein 70
Authors: Tian Weiwei , Qiao Zhenhua , Ye Fang 
Published: October 2019

Abstract
Abstract 4713

Objective
DNA vaccination respresents a novel therapeutic strategy for cancer. Researchs have showed DNA vaccines encoding Wilms tumor gene WT1-Derived HLA *0201-restricted epitopes effectively induce epitope-specific human cytotoxic T-lymphocytes (CTLs) and kill human leukemia cells in vitro. Nevertheless, there is still a need to increase the potency of DNA vaccine and span the HLA diversity of a target population. In this study, we designed polytpoe WT1 DNA vaccine encoding multiple CTL and helper T-lymphocyte (HTL) epitopes and containing HSP70407-426 as immunoadjuvants for immunotherapy.

Methods
On the basis published data, To design a Multi-epitope gene (Multi-WT1) containing three HLA *0201-restricted, one HLA *2402-restricted epitopes, two HTL epitopes and one universal Th Pan- DR epitope (PADRE) sequence. The construct also included IgG K chain leader sequence as signal peptide to facilitate transport into the endoplasmic reticulum and Kozak sequence at the N-terminus to support translation of the gene transcript. DNA-coding sequesces was used computer-based modeling to optimize proteasome mediated epitope processing through the introdcution of amino acid spacer sequences, then cloned into the eukaryotic vector to construct the plasmid PcDNA3.1(+). Mycobacterial HSP70 fragment including stimulatory domain P407-426 as immunotherapy was fused to the C-terminal of Multi-WT1 for enhancing CTL activity and then inserted to PcDNA3.1(+). Transfection HEK-293T cells with the Multi -WT1-HSP70 and identify the expressed product by Western bolt.

Results
Most of Multi -WT1 epitopes can be cleaved by software Net Chop 3.1 and PAPROC± analysis. Western blot showed correct expression of target gene in HEK293T cells.

Conclusion
Multi-WT1-mtHSP70 fusion gene eukaryotic expression vector was successfully designed, which prepared the materials for the research of DNA vaccine.

Disclosures:
No relevant conflicts of interest to declare.
Association of Langerhans Cell Histiocytosis with Erdheim-Chester Disease: How Close Monocyte/Macrophage and Dendritic Cell Lineages Are?
Authors: Hervier Baptiste , Haroche Julien , Hermine Olivier , Donadieu Jean , Charlotte Frederic , Brousse Nicole , Hachulla Eric , Amoura Zahir 
Published: October 2019

Abstract
Abstract 4716

Objectives
Histiocytoses are a heterogeneous group of diseases that can be classified into either Langerhans cell histiocytosis (LCH) or non-Langerhans cell histiocytosis. The latter includes Erdheim-Chester disease (ECD). This study investigated the clinical association between LCH and ECD.

Methods
This retrospective study included 16 patients (10 males, 6 females, median age 41 years) treated at twelve different university hospitals between 1970 and 2010. Inclusion criteria were biopsy-proven LCH in association with two or more diagnostic signs of ECD.

Results
LCH and ECD were diagnosed simultaneously in 4/16 cases, whereas LCH preceded ECD in 12/16 cases. The median time interval was 7.5 years (range 2–22) in these cases. Major organs involved in LCH were the bones (n=12), skin (n=8) and lungs (n=3). ECD mainly affected the large vessels (n=11), bones (n=11) and retroperitoneum (n=9). Non-biopsy proven central nervous system (n=6) and pituitary gland (n=6) involvement also occurred. No specific histologic features were identified in the 65 biopsies studied, including platelet-derived growth factor receptor β expression. Between one and four lines of treatment were required in nine patients diagnosed with LCH. Nine patients were treated with interferon α-2a after the diagnosis of ECD was made. A partial improvement occurred in all assessable patients concerning ECD (n=5) and/or LCH (n=2). These 16 patients were compared with a monocentric cohort of 48 ECD patients; the only difference between the groups was a lower frequency of bone involvement in ECD patients with concomitant LCH (9/13 vs 47/48, p<0.003).

Conclusions
This study suggests that a pathogenic link exists between LCH and ECD. Although the mechanisms responsible for both diseases remain unknown, the present association could argue for transitions between monocyte/macrophage and dendritic cell lineages. The patient characteristics of LCH in association with ECD were similar to those in patients with LCH alone, whereas bone involvement may have been less common in ECD when it was in association with LCH. Clinicians should be aware of this association and should consider the possibility of ECD in patients with LCH, especially in the case of treatment resistance.

Disclosures:
No relevant conflicts of interest to declare.
Clopidogrel, a P2Y12 Receptor Antagonist, Potentiates the Inflammatory Response In An Animal Model of Erosive Arthritis
Authors: Garcia Analia E , Mada Sripal , Rico Mario C , De La Cadena Raul A. , Kunapuli Satya 
Published: October 2019

Abstract
Abstract 4721
The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists. The active metabolite of clopidogrel, a widely used anti-thrombotic drug, irreversibly antagonizes the P2Y12 receptor. However, treatment with clopidogrel has been associated with joint inflammation. In addition, Boilard E. et al identified micro-particles generated by activated platelets in joint fluid from rheumatoid arthritis (RA) patients. In this study we investigated whether platelet activation leads to changes in inflammatory responses using a rat model of erosive arthritis. Here, we evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced arthritis model with four groups of eight rats each: untreated group, animals receiving clopidogrel (clopidogrel group), animals receiving PG-PS (PG-PS group), and animals receiving PG-PS as well as clopidogrel (PG-PS + clopidogrel group). There were significant differences between the PG-PS + clopidogrel treated group when compared to PG-PS treated group including: increased joint diameter [4.24 ± 0.73 vs. 2.70 ± 1.09; p<0.05], clinical manifestations of inflammation, elevated leukocytes count [14.19 ± 0.2 K/uL vs. 9.7 ± 1.4 K/uL; p<0.05] at the expense of neutrophils, increased platelet count [926 ± 195 K/uL vs. 561.25 ± 97 K/uL; p>0.05], and elevated plasma levels of pro-inflammatory cytokines such as IL-1beta, IF gamma, IL-6. Plasma levels of anti-inflammatory cytokine IL-10 were significantly lower in PG-PS + clopidogrel treated group compared to PG-PS group alone. Histological observations indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation and decrease in bone mass upon treatment with clopidogrel in PG-PS-induced arthritis animals. Accordingly to the clinical, histological and cytokine results, we conclude that clopidogrel has a pro-inflammatory effect in PG-PS-induced arthritis animal model and this might implicate that P2Y12 receptor antagonism might enhance inflammatory responses.

Disclosures:
No relevant conflicts of interest to declare.
Clinical, Genetic Characteristics and Geographical Distribution of Gaucher Disease In Iberian Peninsulae and Islands
Authors: Giraldo Pilar , Alfonso Pilar , Irún Pilar , Chabas Amparo , Villageliu Lluisa , Grinberg Daniel , Miranda Clara Sa , Pocovi Miguel 
Published: October 2019

Abstract
Abstract 4729

Background and Objective:
The actual population of Iberian Peninsula (IP) is about 55 millions of inhabitants with a combination of various ethnic groups There are several reports that have analyzed GBA mutations in specific IP population. The aim of this study is to describe the distribution and main clinical characteristics of GD patients in IP.

Patients and Methods:
Data from the National Spanish Gaucher Disease Registry, Genetic Department of Barcelona University and Genetic Medical Institute of Porto since 1970 were jointed. Statistical analysis of demographic data, geographical distribution of GBA mutations and allelic frequency of GBA mutations in IP were analyzed. As well as identified the existence of clusters and the distribution of different types, the type and years on therapy. In addition we have determined the age at diagnosis (aDx) and SSI.

Results:
The prevalence of GD in IP had been 436 diagnosed patients, 421 of them born in IP. The mean aDx was 26.3±19.88 y, there are not differences between aDx before and after the last decade (24.8 vs 26.9 years respectively). Gender: female: 47.74 %, male: 47.98%, unknown: 4.28% type 1: 375 (89.1%), type2: 27(6.4%), type3: 19(4.5%). Mean SSI in type1 GD was 7.7 (range 1–30), and the distribution was 72.7% mild, 25.5% moderate and 1.7% severe. We have identified 70 alleles and 76 different mutations. The most prevalent allelic frequencies were: N370S: 48.8%, L444P: 18.3%, D409H: 3.1%, G3877S: 2.9%, double mutation: L444P+E326K: 2.0%, which account the 75% of total alleles, in 3.3% of alleles the mutation has not been yet identified and the remaining alleles corresponding to private mutations. Nevertheless the most frequent IP genotypes were N370S/L444P, 27.8%, N370S/N370S, 15%, N370S/? 5.2%, G377S/D409H, N370S/G202R, N370S/c.84insG, 2.4% respectively and homozygous for L444P 2.1%. Both Spain and Portugal the most prevalent mutations were N370S and L444P, however N370S is more frequent in Portugal than in Spain (57.1% vs 46.5%) by contrast L444P is more frequent in Spain than Portugal (19.4% vs 14.3%). 247 patients (58.7%) have received ERT for a mean of 10.2±3.89 years and 53 (12.6%) has been treated with miglustat for a mean of 2.1±1.9 years. The 90.4% of type1 and 31.0% of type 3 are alive and all type 2 are dead.

Conclusions:
There are broad spectrums of GBA mutations in GD patients from IP. Five different mutations account for 75% of GBA mutant alleles including N370S, L444P, D409H and G377S. No differences in gender distribution and tendency of aDx were observed. The 98.2% of type1 GD has a mild or moderate grade of severity and 23.0% has never received ERT or SRT.

Disclosures:
No relevant conflicts of interest to declare.
CD11b+gr-1+ myeloid Derived Suppressor Cells (MDSC) In Normal Bone Marrow Suppress T Cell Proliferation and Enhance T-Regulatory Function Via a IL10-, IL4- and IDO-Independent Mechanism
Authors: Forghani Parvin , Harris Wayne , Li jian-Ming , Khorramizadeh M.R. , Waller Edmund 
Published: October 2019

Abstract
Abstract 4801
MDSC have been described as an important negative regulators of autologous anti-cancer immune responses. Considering the important role of MDSC in immune regulation in allogenic stem cell and organ transplantation, we undertook an investigation of the mechanism(s) by which MDSC inhibit T–cell activation and proliferation, and tested the hypothesis that local cytokine secretion or IDO activity is required for suppression of T-cell proliferation.
Two separate populations CD11bhiGr-1hi and CD11bhi Gr-1int were isolated by high-speed FACS from lineage- BM antigen presenting cells (C57 & BALB/c mice). Both MDSC subsets had potent capacity for in–vitro suppression of CD4+ and CD8+ T cells proliferation in response to anti-CD3/anti-CD28 beads and Con A. A ratio of 0.5/1 MDSC: T-cells were sufficient to inhibit >66% control levels of T-cell proliferation. MDSC isolated from transgenic mice that had been “knocked-out” for IFN-γ and IDO had equivalent suppressive activity as MDSC from wild-type donors. Addition of saturating concentrations of anti IL-10 and IL-4 MAb, or in combination with anti- IFN-γ MAb did not abrogate MDSC-suppressive activity. Ex-vivo culture of MDSC with mitogen-activated T-cells generated two—fold more Fox-p3 T-reg compared with cultures of T cell plus mitogen.
Data will be presented regarding the novel role of MDSC involving in the homeostasis regulation of normal T-cell activation and proliferation in non-tumor-bearing mice.

Disclosures:
No relevant conflicts of interest to declare.
Vitamin D Deficiency In Pediatric Patients with Sickle Cell Disease Correlates with Reticulocytosis but Not with Clinical Disease Severity
Authors: Winters Amanda C , Kruse-Jarres Rebecca , Kanter Julie 
Published: October 2019

Abstract
Abstract 4820
Vitamin D deficiency is an established phenomenon in both adult and pediatric patients with sickle cell disease. Between 33% and 78% of children and between 60% and 100% of adults with sickle cell disease (HbSS, HbSC, and HbSβ-thalassemia) have been found to have low serum levels of 25-hydroxyvitamin D, the form most clinically useful for measuring total body levels of vitamin D. Proposed factors contributing to low vitamin D levels in these patients include decreased exposure to sunlight secondary to chronic illness and frequent hospitalizations, malnutrition or malabsorption of vitamin D, higher requirements for vitamin D in sickle cell disease, and impaired metabolism of vitamin D. However, very little data has been published demonstrating a correlation between vitamin D deficiency and burden of disease in patients with sickle cell disease. In addition, there is no published data regarding the effect of vitamin D supplementation on patient-oriented outcomes. We retrospectively reviewed the medical records of pediatric patients with sickle cell disease (ages 0–18 years) to evaluate their serum vitamin D levels as a function of red blood cell turnover, patient's age, and factors relating to burden of disease such as number of emergency room visits and hospital admissions related to vaso-occlusive crises. As expected, we found that essentially all of our patients have insufficient levels of vitamin D at baseline. Although no correlation was seen between vitamin D levels and either age or number of hospital visits related to pain crises, reticulocytosis was significantly correlated (p=0.017) with degree of vitamin D deficiency in our patient population in multiple regression analysis. Based on these preliminary data, vitamin D deficiency in patients with sickle cell disease is more likely the result of the disease process as measured by red blood cell turnover as opposed to the previously hypothesized environmental constraints associated with pain crises and frequent hospitalization. Future analysis will be directed at confirming these findings in adult patients and at evaluating the effects of vitamin D supplementation in both adult and pediatric sickle cell patients. Additional studies should also evaluate the pathogenesis of vitamin D deficiency in states of high red blood cell turnover.

Disclosures:
No relevant conflicts of interest to declare.
Evaluation of TNF Superfamily Molecules Release by Neutrophils and B Leukemic Cells of Patients with Chronic B – Cell Lymphocytic Leukemia
Authors: Sawicka-Powierza Jolanta , Jablonska Ewa , Kloczko Janusz , Piszcz Jaroslaw , Garley Marzena , Ratajczak-Wrona Wioletta 
Published: October 2019

Abstract
Abstract 4855
It was demonstrated that TNF superfamily proteins may affect significantly the time of leukemic cells' survival in the course of B-cell chronic lymphocytic leukemia (B-CLL).
The aim of our study was to evaluate the expression and release of BAFF (B-cell activating factor), APRIL (a proliferation-inducing ligand) and TRAIL (TNF-related apoptosis inducing ligand) molecules belonging to the cytokines of the superfamily of the tumor necrosis factor (TNF) by neutrophils (PMNs) and, for comparison, B cells isolated from the blood of patients with B-CLL vs. their concentration in the blood serum.
40 patients suffering from B-CLL and a control group of 15 healthy subjects were included in the study. Cytoplasmic fractions of PMNs and B cells were analyzed with the use of western blotting for the presence of TRAIL, BAFF and APRIL. Soluble TRAIL, BAFF and APRIL in the culture supernatants and the serum were assessed using ELISA kits.
PMNs and B cells of patients with B-CLL before treatment demonstrated the statistically significantly higher expression of APRIL and BAFF proteins in comparison in relation to the control group of healthy subjects. In contrast, the expression of TRAIL protein in both types of cells of patients was statistically significantly lower than its expression in the control cells.
In the supernatants of PMN and B lymphocytes of patients the decreased concentrations of sBAFF, unchanged of APRIL and increased of sTRAIL molecules were demonstrated.
The results of studies carried out in patients with B-CLL before treatment indicate that the relations demonstrated between APRIL, BAFF and TRAIL molecules, released by neutrophils and B cells and relations between their concentrations in the serum can significantly influence the development of B-CLL.

Disclosures:
No relevant conflicts of interest to declare.