bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS1577 PLATELET COUNT AND MEAN PLATELET VOLUME IN ACUTE STROKE: A SYSTEMATIC REVIEW AND META‐ANALYSIS
Authors: Shemirani H.A. , Sadeghi F. , Kovács S. , Zsóri K.S. , Bereczky Z. , csiki Z. 
Published: June 2019

Background:Changes of platelet count (PC) and mean platelet volume (MPV) could be a marker or a predictor of acute stroke (AS).Aims:We conducted a systematic review and meta‐analysis of the published literature on the reporting of MPV and PC in AS.Methods:Medline, EBSCOhost, Web of Science, ScienceDirect, Google Scholar and Scopus were searched for studies. Studies were included in accordance with Patient Population or Problem, Intervention, Comparison, Outcomes, and Setting (PICOS) framework. The PRISMA strategy was used to report findings. Risk of bias was assessed with Newcastle‐Ottawa Scale. The inclusion criteria were case‐control or cross‐sectional studies, individuals suffered an acute stroke, with fatal or non‐fatal stroke outcomes. Standardized mean difference (SMD) was calculated with a confidence interval of 95% (95% CI).Results:We included 32 eligible articles retrieved from the literature. PC was significantly lower in AS patients [standardized mean difference (SMD) = 0.30, (95%CI: 0.49–0.11), N = 2492, P = 0.002] compared with controls (N = 3615). The MPV was significantly higher [SMD = 0.51, (95%CI: 0.27–0.74), N = 2413, P < 0.001] compared with controls (N = 3621). Subgroup analyses showed significantly lower PC in both ischemic stroke (Difference SMD = 0.18, 95%CI: 0.35‐0.01) and hemorrhagic stroke (0.94, 1.62–0.25), but only samples by citrate anticoagulant showed significantly lower result for patients compared to controls (0.36, 0.68–0.04). Ischemic stroke patients had higher MPV (0.55, 0.29–0.81), and samples by EDTA anticoagulant showed significantly higher result for patients compared to controls (0.79, 0.49–1.10).Summary/Conclusion:PC and MPV appeared to be significantly different between patients with AS and control populations. MPV was significantly higher in ischemic stroke and PC was significantly lower in both ischemic and hemorrhagic strokes. It is advisable to pay attention to the type of anticoagulant for hematology analyses in AS. Our results highlight the potential predictive role of PC and MPV in the occurrence of stroke.
PS1582 DECREASED PLATELET REACTIVITY IS ASSOCIATED WITH AN INFLAMMATORY STATUS IN PATIENTS WITH CANCER
Authors: Riedl J. , Salzmann M. , Pabinger I. , Ay C. 
Published: June 2019

Background:Decreased platelet reactivity was observed in cancer patients at high risk of venous thromboembolism (VTE) and death. Prothrombotic and inflammatory mechanisms have been suggested to cooperate in the development of VTE, representing represent the hallmark of thromboinflammation.Aims:To assess whether platelet reactivity is associated with inflammatory parameters in cancer patients.Methods:Platelet reactivity was determined by whole blood flow cytometry in 62 newly diagnosed cancer patients (median age [interquartile range, IQR]: 63 [54–70] years, 48 % female) at several time points during the first 6 months of chemotherapy (total number of samples analyzed: 179). We measured platelet surface P‐selectin and activated glycoprotein (GP) IIb/IIIa expression in vivo and upon ex vivo stimulation with agonists of protease‐activated receptor (PAR) −1, −4, and GPVI. C‐reactive protein (CRP) and fibrinogen levels were analyzed in plasma samples from the corresponding blood draws.Results:Platelet reactivity, as determined by percentage of platelets expressing activated GPIIb/IIIa on the surface, upon stimulation with different agonists, correlated with significantly lower levels of CRP and fibrinogen (Table 1). Platelet surface P‐selectin expression upon stimulation of the GPVI receptor also showed a significant inverse correlation with CRP and fibrinogen (Table 1). Platelet activation in vivo (i.e. without ex vivo agonist activation) did not correlate with CRP and fibrinogen levels (Table 1).Summary/Conclusion:Our data indicate that there is an inverse relationship between platelet reactivity and inflammatory status in cancer patients, whereby platelets of patients with increased inflammatory parameters are less reactive to stimulation with platelet agonists. Further research is needed to better understand underlying pathophysiological mechanisms.image
PS1595 PREVENTING ALLOIMMUNIZATION OF RECIPIENTS WITH SELECTING OF DONORS BY RED BLOOD CELLS ANTIGENS OF THE RHESUS SYSTEM
Authors: Butina E. , Poponina E. , Yovdiy A. , Sherstnev F. , Zaitseva G. , Paramonov I. 
Published: June 2019

Background:In April 2013, the Ministry of Health of the Russian Federation approved an order regulating transfusion therapy in hematology patients only taking into account the compatibility of the donor and recipient for the antigens C, c, E, e, CW.Aims:Assess the effectiveness of organizational measures for the prevention of alloimmunization to antigens of red blood cells in patients receiving intensive hemocomponent therapy.Methods:The results of immunohematological studies were analyzed in 3697 patients: 1961 patients were first admitted for treatment at a hematological clinic from 2007 to 2014; 1736 patients ‐ from 2015 to 2018. Non‐Hodgkin lymphoma was diagnosed in 767 patients, chronic myeloid leukemia in 220, chronic lymphocytic leukemia in 320, acute leukemia in 612, multiple myeloma in 398, myelodysplastic syndrome in 73, aplastic anemia ‐ in 147, other hematologic diseases ‐ in 1160. The studies were performed using equipment and reagents from BioRad (USA).Results:In 2007–2014, antibodies to antigens C, c, E, e, CW of the Rhesus system were detected in hematological patients with a frequency of 0.92%. Due to the phenotypic selection of donors, the level of alloimmunization decreased 2.6 times and amounted to 0.35% in 2015–2018 (χ2 = 3,831; p = 0.05). The frequency of detection of antibodies to antigen C (0.25% and 0.06%, respectively) and to antigen E (0.46% vs 0.12%) decreased four times. The selection for the antigen was carried out in the clinic since 1998, therefore the immunization index for this antigen remained at the same level (0.10% vs 0.12%). The frequency of detection of antibodies to the CW antigen has not changed significantly (0.10% vs 0.06%). Alloantibodies to the antigen e were not detected for the entire observation period.Table. The frequency of detection of antibodies to antigens C, c, E, e, CW in hematological patients in the periods 2007–2014, 2015‐2018.Summary/Conclusion:Phenotypic selection of donors for antigens C, c, E of the Rhesus system is an effective method of preventing aloimmunization of patients receiving intensive hemocomponent therapy. The selection of red blood cells for antigens CW and e has no practical significance.image
PS1596 AUTOIMMUNIZATION AND ALLOIMMUNIZATION IN TRANSFUSION DEPENDANT THALASSEMIA MAJOR PATIENTS:STUDY ON 300 PATIENTS
Authors: Younas A. , Ghias A. , Farhan S. 
Published: June 2019

Background:Thalassemia is the most common genetic disorder worldwide and one of the major public health problems. Thalassemia patients are dependent on blood transfusions for their survival but they may be associated with many complications. Development of anti red blood cell antibodies(bot alloantibodies and autoantibodies) is one of them. There is a paucity of data on the incidence of alloimmunization and autoimmunization in thalassemic patients in Pakistan,as pre transfusion antibody screening is not routinely performed. Autoantibodies can result in clinical hemolysis and difficulty in cross matching blood. We studied the frequency of Red cell alloimmunization and autoimmunization among Thalassemia patients who received regular transfusions at Sundas Foundation and also to determine types of these antibodies among Thalassemia patients.Aims:To study the frequency of Red Cell alloimmunization and autoimmunization among multiple transfused Thalassemia patients and to determine the types of these antibodies.Methods:A total of 300 multiple transfused Thalassemia patients were included in this study. Clinical and serological records of all the patients were examined. Screening and identification of antibodies was performed on fresh serum of all patients using 3 cell and 11 cell panel respectively. Detection of autoantibodies was done using using polyspecific Coombs(IgG+C3d) gel cards. Approval of this study was taken from the institutional review board. Informed consent was provided.Results:We identified alloantibodies in 17 patients,the most common were Anti E followed by Anti D,Anti C,Anti K,Anti Fyb,Anti‐M.4 patients developed autoantibodies.Summary/Conclusion:Alloimmunization is an immune respone stimulated by the transfusion of blood products. Overall rate of alloimmunization was 5.66% in our study while it is 30%/190 in Kuwait,4.97%/161 in India,5%/1435 in Italy,3.7%/1200 in Greece,5%/711 in Iran,9.2%/97 and 22.7%/75 in Pakistan.
S1599 RITUXIMAB MAINTENANCE FOR PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA IN FIRST COMPLETE REMISSION: RESULTS FROM A RANDOMIZED HOVON‐NORDIC LYMPHOMA GROUP PHASE III STUDY
Authors: Lugtenburg P. , Brown P. , van der Holt B. , D’Amore F. , Koene H. , de Jongh E. , Fijnheer R. , Loosveld O. , Böhmer L. , Pruijt H. , Verhoef G. , Hoogendoorn M. , Bilgin Y. , Nijland M. , Lam K. , de Keizer B. , de Jong D. , Zijlstra J. 
Published: June 2019

Background:This randomized phase III trial assessed whether intensification of rituximab (R) during the first 4 cycles of R‐CHOP can improve outcome of diffuse large B‐cell lymphoma (DLBCL) patients compared with standard R‐CHOP. Patients in complete remission (CR) after induction treatment were randomized between rituximab maintenance and observation. Intensification of rituximab was not more effective than standard R‐CHOP, showing same CR‐rates and progression free survival after induction (ASCO 2016 # 7504). Here, we report the results of the second randomization for rituximab maintenance therapy.Aims:To assess in a prospective, multicenter, randomized phase III study in patients with DLBCL the efficacy of maintenance treatment with rituximab in comparison to no further treatment on disease free survival.Methods:Patients in CR after R‐CHOP were randomized between 24 months of rituximab maintenance 375 mg/m2 intravenous every 8 weeks (n = 199) or observation (n = 199). CT scans were performed at 6, 12, 18 and 24 months in both arms. The primary endpoint was disease free survival (DFS) from maintenance randomization. Secondary endpoints were overall survival (OS) and adverse events (AEs). (www.trialregister.nl NTR1014).Results:Median age was 65 years (range 31–80), 48% were 66 years or older and 49% were male. The majority of patients (54%) had a high‐intermediate or high aa‐IPI score. After a median follow‐up of 79.9 months (maximum 125.7 months), the 5‐year DFS rate was 79% for rituximab maintenance versus 74% for observation. This difference was not statistically significant, with a hazard ratio of 0.83 (95% confidence interval 0.57–1.19, p = 0.31, adjusted for age and aa‐IPI). The secondary endpoint OS was also not significantly different (85% versus 83% at 5 years). No clinical subgroup benefited from rituximab maintenance. Toxicity was mild. Among patients who received rituximab maintenance CTCAE grade 3 and 4 AEs were reported in 17% and 6% of patients, respectively. Infection was the most frequent AE, a grade 3 infection occurred in 6% of patients. Neutropenia was seen in 1% (grade 3) and 3% (grade 4) of patients.Summary/Conclusion:Rituximab maintenance therapy provides no additional benefit for DLBCL patients in first CR after R‐CHOP.
S1623 INTESTINAL MICROBIOTA CAN PREDICT AGVHD FOLLOWING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Han L. , Zhang H. , Chen S. , Zhao K. , Huang F. , Fan Z. , Jin H. , Jiang Z. , Liu Q.‐F. 
Published: June 2019

Background:The intestinal microbiome plays an important role in the development of acute graft‐versus‐host disease (aGVHD), and loss of microbiota diversity is associated with aGVHD. However, it has been rarely reported whether the intestinal microbiota at neutrophil engraftment could predict the occurrence and grades of aGVHD.Aims:We collected stool and blood samples from 141 patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at pre‐conditioning, day 0 and day 15 post‐transplantation. The microbiota in stool were detected by 16S rRNA gene sequencing; the inflammatory factors in blood were detected by multiplex immunoassays and dynamic turbidimetric methods; and T lymphocyte subsets were tested by flow cytometry.Methods:The microbiota diversity was lower in the aGVHD group compared with non‐aGVHD group at day 0 and day 15 ± 1 (P = 0.018 and 0.009, respectively). Diversity was associated with conditioning (P = 0.017, day 0 and P = 0.045, day 15) and β‐lactam antibiotics (P = 0.004, day 15). The Treg/Th17 ratio in blood was positively correlated with microbial diversity (r = 0.216, P = 0.010), while it was negatively correlated with the levels of TNF‐α, IL‐17A, IL‐1β and LPS in plasma (r = −0.226, −0.225, −0.335, −0.291; P = 0.007, 0.010, < 0.001, < 0.001, respectively) at day 15 post‐transplantation. In addition, the accumulated intestinal microbiota (AIM) score at day 15 could be a predictor for the development of aGVHD (II‐IV aGVHD: AUC = 0.75, P < 0.001; III‐IV aGVHD: AUC = 0.84, P < 0.001). The AIM score was also correlated with aGVHD grades (r = 0.481, P < 0.001).Results:These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment can predict the subsequent development and grades of aGVHD.Summary/Conclusion:These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment can predict the subsequent development and grades of aGVHD.
S1629 ERFE‐A260S ACCOUNTS FOR HEPATIC IRON METABOLISM IMPAIRMENT BY ACTING ON THE BMP‐SMAD PATHWAY
Authors: Andolfo I. , Manna F. , De Rosa G. , Rosato B.E. , Marra R. , Gambale A. , Iolascon A. , Russo R. 
Published: June 2019

Background:Iron overload is a major clinical challenge in the management of hereditary ineffective erythropoiesis ‐related anemia (iron‐loading anemia). To coordinate iron metabolism with hemoglobin (Hb) synthesis, erythropoietin (EPO)‐stimulated erythroid precursors release erythroferrone (ERFE), a soluble protein that suppresses the expression of hepcidin. Hepcidin is a hormone that controls iron entry into the circulation by blocking the iron exporter ferroportin.Congenital dyserythropoietic anemia type II (CDAII) is a bone marrow failure anemia characterized by mono‐lineage cytopenia and morphological abnormalities of erythroid precursor cells. The marked clinical variability observed in CDAII patients is related to its major complication, the iron overload associated with reduced expression of hepatic hormone hepcidin. We recently analyzed ERFE expression in both CDAII patients and in vitro model, demonstrating that in CDAII patients ERFE is overexpressed and related to abnormal erythropoiesis.Aims:To study possible modifier genes affecting the iron overload phenotype in CDAII.Methods:t‐NGS custom panel; genotyping; cells culture and transfection assays; qRT‐PCR; immunoblotting.Results:We herein identified a recurrent low‐frequency variant, A260S, in ERFE gene in 12.5% of CDAII patients showing severe phenotype by our 81‐genes target custom panel for modifier genes. We demonstrated that ERFE‐A260S variant leads to an increased expression of ERFE. We further characterized the effect of ERFE‐A260S in an in vitro human hepatic model, HuH7 cells, showing a marked impairment of iron regulation pathways by inhibition of phosphorylation of SMAD1/5/8 and consequent downregulation of the expression of BMP/SMADs pathway target genes: HAMP, ID1, ATHO8 and SMAD6.Summary/Conclusion:We herein described for the first time an ERFE polymorphism as modifier variant with a mild effect on disease expression under a multifactorial‐like model in a condition of iron‐loading anemia due to ineffective erythropoiesis. This is a novel paradigm that paves the ways to new investigations for evaluating the role of this ERFE variant as a modifier in many other related pathological conditions, as b‐thalassemia intermedia. Moreover, the discovery of the genetic basis of CDAII and its major complication, iron overload, will lead us to expand our understanding of the biology of ineffective erythropoiesis and to provide initiative for further investigation of new therapeutics. Indeed, ERFE is currently a candidate target for therapeutic inhibition, in iron loading anemia.
PB1653 HIGH RASD1 TRANSCRIPT LEVELS AT DIAGNOSIS PREDICTED POOR SURVIVAL IN ADULT B‐CELL ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS
Authors: Wang S. , Wang C. , Liu Y. 
Published: June 2019

Background:B‐cell acute lymphoblastic leukemia (B‐ALL) in adults remains a highly challenging disease. Identifying new prognostic biomarkers is necessary to help select the best therapeutic schedules and to improve prognosis. We performed bioinformatics analyses of transcriptomic data to identify aberrantly‐expressed mRNA transcripts in B‐ALL and focused on RASD1 (Ras‐related dexamethasone‐induced 1) which is a member of the RAS family and plays important roles in tumor growth and expansion. To date, no reports on RASD1 and B‐ALL have been reported.Aims:To examine the expression and clinical significance of RASD1 in adults with B‐ALL; to explore effects of RASD1 on biological function of B‐ALL.Methods:Fifty‐three consecutive adults with de novo B‐ALL were enrolled in this study. The RASD1 transcript levels were determined by TaqMan‐based real time quantitative PCR (RQ‐PCR) at the time of diagnosis. RASD1‐over‐expression cell models were constructed to study the biological function of RASD1 in B‐ALL. The cell proliferation was detected by CCK‐8; cell apoptosis and cell cycle were analyzed by flow cytometry.Results:Our data suggested that RASD1 was abnormally overexpressed in B‐ALL. High RASD1 transcript levels at diagnosis were associated with lower survival probabilities (44% [20% > 61%] vs. 79% [60% > 97%]; P = 0.037) and were also an independent prognostic factor in adult B‐ALL (HR = 4.9 [1.5‐15.9]; P = 0.008). Functional in vitro analyses indicated that RASD1 promoted cell proliferation, cell cycle progression and chemotherapy resistance and inhibited cell apoptosis. Bioinformatic analyses also showed that high RASD1 expression in cells correlated with positive regulation of cell proliferation as well as nucleosome assembly and telomere organization.Summary/Conclusion:These data demonstrated that RASD1 might serve as a novel prognostic biomarker for adult B‐ALL and as a potential therapeutic target in adult B‐ALL patients.
PB1661 CHARACTERIZATION OF A DUX4‐IGH INHIBITOR AS A POSSIBLE TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Salome’ M. , Caronni C. , Runfola V. , Giambruno R. , Campolungo D. , Ghirardi C. , Gabellini D. 
Published: June 2019

Background:B cell acute lymphoblastic leukemia (B‐ALL) is the most common pediatric cancer and the major cause of cancer‐related death before the age of 20. In up to 7% of cases, the disease is caused by rearrangements of the Double Homeobox 4 (DUX4) transcription factor to the immunoglobulin heavy chain (IGH) locus, giving rise to the oncogenic fusion protein DUX4‐IGH. While ectopic expression of wild type DUX4 induces apoptosis, DUX4‐IGH has transforming ability in cellular and animal models. These opposite biological activities are mirrored by the ability of DUX4 and DUX4‐IGH to drive the transcription of non‐overlapping sets of target genes, despite the two proteins share the same DNA binding domain (dbd).Aims:Through proteomics, we identified a specific DUX4‐IGH inhibitor. Preliminary data indicate that the inhibitor directly binds to DUX4‐IGH dbd blocking the activation of target genes. Based on this evidence, I aim to test the antileukemic activity of the inhibitor.Methods:Human cell lines and primary murine bone barrow progenitor cells will be lentivirally transduced to induce the expression of DUX4‐IGH alone or in combination with its inhibitor, and the effects on proliferation, transformation, clonogenic potential and self‐renewal ability in B‐cell differentiation conditions will be evaluated.To test the efficacy of DUX4‐IGH inhibition in leukemia development, I will employ murine bone marrow transplantation assays and patient derived xenografts of DUX4‐IGH B‐ALL and assess disease latency in the presence or absence of the DUX4‐IGH inhibitor.Results:Preliminary data indicate that the activity of DUX4‐IGH is restricted to B‐cells, supporting the need of a B‐cell specific co‐factor. Importantly, lentiviral expression of the DUX4‐IGH inhibitor in NALM6 cells that carry a DUX4‐IGH translocation reduce the endogenous levels of DUX4‐IGH targets.I expect to see a significant inhibition of DUX4‐IGH driven transformation in the presence of its inhibitor, associated with reduced proliferation, clonogenic and self‐renewal potential in cell culture systems. I predict that the inhibitor will rescue differentiation potential and block or significantly delay leukemia development in mice injected with DUX4‐IGH expressing pro‐B cells.Summary/Conclusion:Pre‐clinical validation of the DUX4‐IGH inhibitor will help defining effective therapeutic strategies for DUX4‐IGH B‐ALL patients, improving clinical outcome and lowering treatment toxicity.