bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Elderly Patients with Hematological Malignancies By Two Different Geriatric Risk Scoring Systems: G8 and Flemish Version of the Triage Risk Screening Tool (fTRST)
Authors: Atilla Erden , Yalciner Merih , Kilic Ozlem , Muftuoglu Nurhayat , Ataca Atilla Pinar , Civriz Bozdag Sinem , Toprak Selami Kocak , Kurt Yuksel Meltem , Özcan Muhit , Gurman Gunhan , Ilhan Osman 
Published: October 2019

Abstract
Background: High burden of patients with hematological malignancies are diagnosed >65 years old. Since then, geriatric interventions can improve quality of life, compliance to therapy and overall survival. Geriatric screening is the best tool to access patients' prognosis. In this study, our aim is to identify our geriatric patients with different geriatric scoring systems to evaluate their prognostic value for overall survival (OS).
Patients and Methods: We included 127 patients (age>65 years) with hematological malignancies and assessed two geriatric screening tools, G8 and Flemish version of the Triage Risk Screening Tool (fTRST) during a hospital visit at diagnosis or follow-up. G8 is considered normal if the score is >14, high risk patients in fTRST are defined as patients scored ≥ 2. OS was described using Kaplan-Meier plots, and comparisons were made using log-rank and Wilcoxon rank sum tests.
Results: From 127 patients, 50 patients (39%) were newly diagnosed. The patient characteristics were defined in table. Patients under follow-up received median of 2 lines of treatment (range, 1-5); 11 patients (14%) treated with radiotherapy, 15 patients (19%) underwent autologous stem cell transplantation. Abnormal G8 score was detected in 120 patients (94%). High fTRST score was present in 72 patients (57%). Both abnormal G8 score and high fTRST score were detected more likely in follow-up patients (65% vs 40%, p=0.005).There was no statistical difference in 5-year OS in terms of abnormal G8 score or high fTRST score alone. In patients with both abnormal G8 and high fTRST scores had statistically significant lower 5-year OS compared to normal G8 and/or low fTRST scores (57% vs 85%, p=0.048) (figure).
Conclusion: In investigation of two screening tools-G8 and fTRST, statistically significant survival advantage was shown if both scores were normal.

Disclosures
Civriz Bozdag: MSD: Research Funding; NOVARTIS: Consultancy; TAKEDA: Consultancy. Özcan:Jazz: Other: Travel support; Roche: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding; Janssen: Other: Travel Support, Research Funding; Celgene: Other: Travel support, Research Funding; Novartis: Research Funding; MSD: Research Funding; Abbvie: Other: Travel payment; BMS: Honoraria; Bayer: Research Funding; Jazz: Other; MSD: Other: travel support, Research Funding; Archigen: Research Funding. Ilhan:BMS: Speakers Bureau; Alexion: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau.
Effects of Splenectomy before Transplantation on β-Thalassaemia Major with Matched Sibling and Unrelated Hematopoietic Stem Cell Transplantation
Authors: Chen Libai , Wen Jianyun , He Yuelin , Ruan Yongsheng , Li Chunfu , Wu Xuedong 
Published: October 2019

Abstract
Purpose:Splenectomy can improve the quality of life of patients with β-thalassaemia major to some extent, but also increase some unpredictable risk.In order to understand the effects of splenectomy before transplantation on hematopoietic stem cell transplantation reconstruction time, infection, graft versus host disease and hepatic veno-occlusive disease of matched sibling and unrelated hematopoietic stem cell transplantation, the following studies were conducted.
Methods:A retrospective analysis of 80 β-thalassaemia major patients in the southern hospital between January 2012 and December 2017 for matched hematopoietic stem cell transplantation, and 35 of them had a splenectomy before the transplant. Cox model adjustment, t test and χ2 test were used to compare the incidence of neutrophil implantation time, hemoglobin implantation time, platelet implantation time, infection, graft versus host disease and hepatic vein occlusion.
Results:Neutrophilic granulocytes and platelets were implanted more rapidly in patients who underwent splenectomy than those who did not (P < 0.05).There was no significant difference in the incidence of infection, graft versus host disease and hepatic vein occlusion.
Conclusion: For level of Ⅱ-Ⅲ β-thalassaemia major patients, hypersplenism can cause delayed reconstruction of hematopoietic stem cell transplantation, while before transplantation splenectomy to speed up the implantation of hematopoietic stem cell transplantation, and does not increase the incidence of complications after transplantation.

Disclosures
No relevant conflicts of interest to declare.
Long-Term Survival after Transplantation in Patients with Chronic Myeloid Leukemia from HLA-Compatible Unrelated Donors: May the Stem Cell Source Influence the Outcome?
Authors: Koldehoff Michael , Elmaagacli Ahmet H. , Ottinger Hellmut Dietmar , Dührsen Ulrich , Beelen Dietrich W. 
Published: October 2019

Abstract
Introduction
Allogeneic hematopoietic stem cell transplantation (alloSCT) is curative therapy for chronic myeloid leukemia (CML), but its long-term outcomes regarding graft sources are not well described.
Results
Here the outcomes of CML after alloSCT with bone marrow (BM, n=134) were compared to those of peripheral blood stem cell (PBSC, n=172) in the HLA-compatible unrelated donor setting. Patients were transplanted in 1st CP (Bone marrow transplantation (BMT), n=100, and Peripheral blood stem cell transplantation (PBSCT), n=103), in >1st CP (BMT, n=24, and PBSCT, n=52) and in blast crises (BMT, n=10, and PBSCT, n=17). Median follow-up were 54 months after BMT and 106 months after PBSCT. No significant differences were found in the incidence of acute and chronic graft-versus-host disease (GvHD) between both study-groups. The 5-year estimated probability of hematological relapse was 11% for patients in 1st CP CML and 49% for patients in advanced disease after BMT (p<0.001) and 18% for patients in 1st CP and 22% for patients in advanced disease after PBSCT (p= n.s.). The estimated probability for 10-year overall survival (OS) for patients in 1st CP and patients in advanced stages of CML were 58% and 20% after BMT and 59% and 52% after PBSCT, respectively (not significant for 1st CP and p<0.0001 for advanced stages). In the multivariate analysis patient age (age > 40 years), disease stage, acute GvHD, chronic GvHD and immunprophylaxis with use of ATG influenced OS significantly. For leukemia-free survival, the following risk factors were significantly in the multivariate analysis, graft source, patient age, gender constellation, disease stage, acute GvHD and chronic GvHD.
Conclusions
This large trial show significant difference between transplant recipients who received PBSC and those who received BM from unrelated donor. These finding may influence the selection of a graft source for alloSCT from unrelated donor.

Disclosures
Dührsen: Amgen: Research Funding; Gilead: Consultancy, Honoraria; Janssen: Honoraria; AbbVie: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Beelen:Medac: Consultancy, Other: Travel Support.
Prognostic Impact of Notch Signaling in Acute Myeloid Leukemia (AML)
Authors: Takam Kamga Paul , Resci Federica , Dal Collo Giada , Adamo Annalisa , Bazzoni Riccardo , Mercuri Angela , Bonifacio Massimiliano , Krampera Mauro 
Published: October 2019

Abstract
Background: Notch signaling is a developmental pathway involved in normal and malignant hematopoiesis. Mutations in Notch genes lead to T-ALL and are associated with poor prognosis in B-CLL. However its role in AML is still under investigation, with controversial results. In addition, although the pathway consists of 4 receptors and 5 ligands, many studies are mostly based on single receptor or ligand.
Aims: This study was conducted to determine if the expression level of each Notch receptor and ligand are associated with known prognostic factors and patient's survival.
Methods: AML primary cells were collected from 79 AML patients after informed consent. The follow-up was for 36 months. Flow cytometry analysis was used to study the expression of each Notch receptor and ligand. Prognostics or risk factors considered were sex, white blood counts, FAB and cytogenetics. The Mann-Whitney test was used for analyzing differences in expression levels between two groups. Spearman test was used for correlation between Notch expression levels and prognostics factors. Differences in overall (OS) and progression free (PFS) survival were established through Gehan-Breslow-Wilcoxon test.
Results: Consistently with previous findings, we found expression of Notch1, Notch2, Notch3, Notch4, Jagged1, Jagged2 and DLL3 in AML samples. There were no differences in expression levels between male and female. For each receptor or ligand, higher expression levels were found in more immature samples (M0, M1, and M2). Notch3, Notch4 and Jagged2 were enriched in adverse cytogenenetics risk groups compared to favorable cytogenetics risk patients. Then, for each receptor or ligand, patients were divided into two groups; patients with higher expression levels and patients with lower expression levels. Analyzing OS and PFS, we found that patients with lower expression levels of Notch4, Jagged2 and DLL3 displayed a longer survival compared to patients with higher expression levels.
Conclusion: Given its oncogenic role in T-ALL and other malignancies Notch1 has been the more studied receptors in hematological malignancies. However, we have previously demonstrated that Notch4, DLL3 and Jagged2 are all involved in survival of AML and B-ALL cells. Studying the prognostic value of all Notch receptors and ligands, the current research clearly shows that higher levels of Notch4 and Jagged2 are found in poor cytogenetics risk groups and are associated with a shorter patient's survival. These demonstrations suggest that expression levels of Notch receptors and ligands in AML patient's samples at diagnostic could stand as prognostic marker for clinical care.

Disclosures
No relevant conflicts of interest to declare.
Single Cell Transcriptomics Maps the Embryonic Emergence of HSC and Identifies Intercellular Interactions Regulating HSC Genesis
Authors: Hadland Brandon , Varnum-Finney Barbara , Dozono Stacey , Jackson Dana , Rafii Shahin , Bernstein Irwin D. , Trapnell Cole 
Published: October 2019

Abstract
Hematopoietic stem cells (HSC) are generated during a transient window of embryonic development from endothelial-like hemogenic precursors within specific arterial vessels such as the aorta of the AGM (aorta-gonad-mesonephros region). During HSC emergence, hemogenic precursors must acquire and maintain HSC-defining properties such as the ability to self-renew, home, and provide multilineage hematopoiesis, properties which distinguish rare HSC from a multitude of other hematopoietic progenitors arising simultaneously in the developing embryo. However, the precise niche-derived signals necessary and sufficient to support the acquisition and maintenance of these properties remains poorly defined. Toward identification of these signals, we generated a platform consisting of endothelial cells from the embryonic AGM (AGM-EC) which supports the specification and self-renewal of engrafting HSC from clonal embryo-derived hemogenic precursors in vitro. Using this platform to assay functional HSC potential at the single cell level, we determined a phenotype (VE-Caderin+CD61+EPCRhigh) that encompasses the population of hemogenic precursors during their asynchronous transition to HSC between E9.5 and E11.5 in murine embryonic development. To elucidate the transcriptional changes associated with the emergence of HSC from hemogenic precursors, we analyzed the global transcriptional profiles of FACS-purified VE-Caderin+CD61+EPCRhigh cells at various stages of embryonic development by single cell RNA-sequencing and reconstructed their developmental trajectory in "pseudotime" based on incremental changes in their transcriptional profiles. Complementary analysis of AGM-EC by bulk and single cell RNA-sequencing revealed a unique transcriptional profile of niche endothelial cells supporting HSC development enriched for immune/inflammatory signals. Combining the transcriptional profiles of emerging HSC with niche AGM-EC, we have identified candidate ligand-receptor pairs regulating intercellular interactions during HSC specification and self-renewal and have begun to validate the functional importance of these interactions in supporting HSC generation from hemogenic precursors in vitro. We expect these studies will enhance our understanding of the unique signal pathways necessary for the development of functional HSC, a critical step toward engineering HSC in vitro for clinical applications in disease modeling, drug discovery, and gene modification to identify novel therapies for hematologic and immunologic disorders.

Disclosures
Rafii: Angiocrine Bioscience: Equity Ownership.
Molecular Analysis of Factor V, Prothrombin and Methylenetetrahydrofolate Redutase in Thrombolic Patients
Authors: Paiva Aldair Sousa , Paiva Hugo Diogenes De Oliveira , Cavalcanti Geraldo Barroso , Leão Gioconda DR , Leão Marcos Dias , Bahia Frank , Vasconcelos Roberto C , Fernandes Andrea LAC , Gil Erica Aires , Soares Victor lima , Januario Geisa , Santos Karla Cristina , Lemos Telma Araujo , Jardim Alessandra Suelen 
Published: October 2019

Abstract
Background: The study of thrombotic events requires knowledge of changes in the hemostatic system associated with multiple acquired and hereditary risk factors that suggest predisposition to thrombosis. The factor V or Leiden (G1621A), Prothrombin (G21210A) and Methylenetetrahydrofolate redutase-MTHFR (C677T) mutations are the major genetic risk factors for venous thrombosis. This study assessed the frequency of mutations of the Factor V (Leiden), Prothrombin and MTHFR in patients with thrombophilia from the DNA Center Laboratory, Natal - RN. Methods: The detection of mutations was made by PCR-RFLP followed by enzymatic restriction with HindIII (Leiden and Prothrombin) and HinfI (MTHFR). Results: From 69 selected patients, 52 (75.36%) were females and 35 (24.64%) were males. The frequency of genotypes for the Factor V were: 3 mutated homozygous (4.35%), 4 heterozygous (5.80%) and 62 normal homozygous (89.85%). Regarding the mutation in the Prothrombin gene it was observed in 65 normal homozygous patients (94.2%) and 4 (5.8%) heterozygous. The analysis of the mutation in the gene MTHFR showed 35 (50.7%) normal homozygous patients, 5 (7.2%) mutated homozygous patients and 29 heterozygotes patients (42.1%). Conclusions: Approximately 50% of patients tested had at least one type of genetic alteration combined. Based on data obtained it is indicated the investigation of three markers (Factor V, Prothrombin and MTHFR) thrombophilia-related, targeting the real impact of the molecular mutations in thrombosis and the conduct of treatment.

Disclosures
No relevant conflicts of interest to declare.
Apixaban, Dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial
Authors: McBane Robert D. , Wysokinski Waldemar E. , Le-Rademacher Jennifer , Ashrani Aneel A. , Tafur Alfonso J , Gundabolu Krishna , Perez-Botero Juliana , Perepu Usha , Anderson Daniel M. , Kuzma Charles , leon Ferre Roberto , Henkin Stanislav , Lenz Charles , Loprinzi Charles 
Published: October 2019

Abstract

Background: Currently, low molecular weight heparin is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients.
Methods: Patients with cancer associated acute VTE were randomly assigned to receive either apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin (200 IU/kg for 1 month followed by 150 IU/kg once daily) for 6 months. The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding.
Results: Of the 300 patients who underwent randomization, 287 were included in the primary analysis. Of these, metastatic disease was present in 65.5% of subjects and 74% were receiving concurrent systemic cancer therapy. Colorectal, lung, pancreas, and breast cancers were the four most prevalent cancer types. Major bleeding occurred in 0 of the 142 patients (0%) in the apixaban group as compared with 3 of the 145 patients (2.1%) in the dalteparin group (p=0.9956). Recurrent VTE occurred in 5 patients (3.4%) in the apixaban group and 20 patients (14.1%) in the dalteparin group (difference in risk -10.7 percentage points) with a Hazard Ratio (HR) 0.26, (95% CI, 0.09 - 0.80, p = 0.0182). Major plus clinically relevant non-major bleeding were similar at 9% for both groups. There were no mortality differences comparing apixaban (15.9%) and dalteparin (10.6%) groups at 6 months (HR 1.36, 95% CI 0.79 - 2.35). Monthly quality of life surveys favored apixaban therapy for many measures including: concern for excess bruising, stress, irritation, burden of delivery, and overall satisfaction with anticoagulant therapy (p<0.05). Monthly bruising questionnaire favored apixaban at each interval (p<0.002).
Conclusions: Oral apixaban therapy was associated with very low rates of bleeding and significantly lower VTE recurrence with superior quality of life outcome measures compared to parenteral dalteparin in the treatment of cancer associated VTE. These data support the clinical utility of apixaban for the acute treatment of VTE in this patient population.
Table. Table.

Disclosures
No relevant conflicts of interest to declare.
Reactivation of Hepatitis B Virus Infection in Aplastic Anemia Patients Receiving Immunosuppressive Therapy
Authors: Yin Hua , Wang Suli , Lu Xingyu , Shen Wenyi , Lu Ruinan , Zhu Yu , Miao Kourong , Hong Ming , Wang Shuai , Zhang Jianfu , Qiao Chun , Wu Yujie , Wu Xuemei , He Guangsheng , Li Jianyong 
Published: October 2019

Abstract

Objective: The aim of this study was to assess the risk of HBV reactivation in HBsAg-positive or negative, HBcAb-positive patients with aplastic anemia (AA) receiving immunosuppressive therapy.
Methods: We analyzed clinical data of 60 AA patients with HBV infection out of 201 cases. Entecavir or lamivudine therapy was initiated if HBV reactivation was encountered, or used as antiviral prophylaxis regimen for HBsAg-positive patients.
Result: Among 60 AA patients, 12 were chronically infected and 48 were previously exposed. There was no difference in clinical features in AA patients with or without HBV infection. The prevalence of non-severe AA (NSAA) progressed to severe AA (SAA) was similar in two groups (35.6% vs 42.7%, p=1.0). In NSAA group, the response rate to CsA, to ATG and CsA, and progression to SAA were similar in patients with or without HBV infection (35.7% vs 35.3%, p>0.05; 42.8% vs 58.8%, p= 1.0; 35.5% vs 42.7%, p= 0.414). In SAA group, patients with or without HBV infection responded to ATG and CsA therapy similarly (83.33% vs 59.0%, p = 0.252). HBV reactivation was occurred in all 5 HBsAg positive patients without any antiviral therapy, while no HBV reactivation happened in other 7 patients received antiviral therapy. Disease course (RR=1.012, p=0.036) and absolute reticulocyte count (RR=11.556, P=0.025) were the risk factors for HBV reactivation by univariate analysis. Logistic regression indicated that HBsAg positivity without preventive therapy was the only strong factor for HBV reactivation.
Conclusion: Antiviral prophylaxis is recommended for HBsAg-positive patients with AA who will receive IST because of high rate of HBV reactivation. HBV infection has no influence on the clinic course of AA, and antiviral therapy does not affect the efficacy of IST.

Disclosures
No relevant conflicts of interest to declare.
Assessment of the Application and Clinical Value of Next-Generation Sequencing for the Diagnosis of Inherited Thrombocytopenia
Authors: Jiang Miao , Wang Qi , Zhao Yiming , Yu Ziqiang , Chen Suning , Xia Lijun , Ruan Changgeng 
Published: October 2019

Abstract
Inherited thrombocytopenia is a group of hereditary diseases with a reduction in platelet count as the main clinical manifestation. Clinically, there is an urgent need for a convenient and rapid diagnosis method. We introduced a high-throughput next-generation sequencing (NGS) platform into the routine diagnosis of patients with unexplained thrombocytopenia and analyzed the gene sequencing results to evaluate the value of NGS technology in the screening and diagnosis of inherited thrombocytopenia.
From a cohort of 182 patients with thrombocytopenia, we screened 78 patients with hereditary features. For the blood samples of these 78 patients, a gene sequencing platform for hemorrhagic and thrombotic diseases comprising 89 genes was used to perform gene detection using NGS technology. When we combined the screening results with clinical features and other findings, 23 of 78 patients (29.5%) were diagnosed with inherited thrombocytopenia. In addition, 29 pathogenic variants, including 11 previously unreported variants, were identified in these patients.
In summary, NGS could play more important role in the molecular pathology diagnosis of inherited thrombocytopenia. Through the use of this detection platform, we expect to establish a more effective diagnostic approach to such disorders.

Disclosures
No relevant conflicts of interest to declare.
Impact of Mhealth and Ehealth Applications on Hemophilia Treatment Management
Authors: Santandreu Estelrich Maria Margalida , Sánchez-Raga José María , Massanet Antonio Palomero , Galmés Sureda Bernat , Delgado Olga , Sampol Antonia , Canaro Mariana 
Published: October 2019

Abstract
Objective:
To evaluate the effect of the implementation of a smart-phone based therapy management application over the monitoring of the hemophilia A (HA) and B (HB) patients in home-care setting.
Setting:
Since 2016 our hospital is using a mobile app and real time therapy management system for hemophilia patients (Haemoassist™, StatConsult) as a new tool of hemophilia patients care management complementing the existing health charts.
Methods:
A retrospective research conducted at one hemophilia treatment center covering four islands. HA and HB patients using the mobile app with at least 6-month follow-up period were included. Data on socio-demographics, clinical and therapy were collected before and after 6-month period of the app introduction. Sources of information were the electronic medical history (Millenium-Cerner™), pharmacy outpatient delivery program (Hospiwin™) and the above mentioned smart-phone app.
The adherence was estimated calculating real factor consumption divided by the theoretical factor consumption according to prescribed prophylactic regimen for each study period. The extra doses for bleeding episodes were collected only after the intervention, due to unavailable reliable reports for mild and moderate bleeding events before the incorporation of the app.
Results:
A total of 28 patients with severe and moderate HA and HB on prophylactic treatment were included. The median age was 25 years (range 3-57). The median of the first period adherence was 72.7 % (range 30.77-100%) and of the second was 100% (range 51.88-100%). The median of the difference between periods was 15% (see chart 1 for more detailed information). In the post-intervention period, 12 (43 %) patients had a median of 3 bleeding events (range 1 -7) and needed extra-infusions with a median of 7 doses (range 3-17).
Conclusions:
The adherence to prophylactic treatment is crucial to reduce joint bleedings (Manco-Johnson MJ et al. NEJM. 2007). The use of therapy management mobile app has contributed to increase adherence in our patients allowing a precise monitoring of the administered factor and bleeding events in real time.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.