Day 2 :
Keynote Forum
Jean-Francois Schved
Montpellier University Hospital, France
Keynote: Pathogenesis of thrombosis in myeloproliferative neoplasms
Time : 09:00-09:40
Biography:
Jean-Francois Schved is a Doctor, Professor of Hematology at Faculty of Medicine of Montpellier. His main theme of study and research is “Haemostasis, especially hemorrhagic disease, hemophilia”. His team has also conducted important scientific work on red blood cells and genetic iron overload. He published more than 200 scientific articles in international journals in collaboration with various units of research or hospital services and participated in writing of many medical books. He regularly participates in conferences in France and abroad on Hemostasis or Transfusion Hematology. He reviews frequently manuscripts for major journals.
Abstract:
Venous or arterial thrombosis are the most frequent complications of myeloproliferative neoplasms, mainly polycythemia vera and essential thrombocythemia. Their pathogenesis has been extensively investigated but is not fully elucidated. They are multifactorial involving quantitative and qualitative red blood cell, platelet and leukocyte abnormalities. Blood hyper viscosity is likely to play a role in polycythemia vera. It induces a high shear stress of the vessel wall and mead to chronic endothelial dysfunction and platelet and leukocyte activation. The development of cell aggregate such as red cells, platelet or leukocyte aggregates may disturb blood flow and cause ischemia in the cerebral vessels. For platelet, high platelet count may not be associated to high thrombotic risk. On the contrary, very high thrombocytosis seems to be associated with hemorrhagic complication. Qualitative platelet changes may be more relevant: both polycythemias vera and essential thrombocythemia subjects were found to have an increased urinary excretion of the major thromboxane A2 metabolites. The role of leukocytes has also been investigated. It’s well known that leukocytosis is an independent risk factor for thrombosis. As for platelets, the role of leukocyte activation may be important as assessed by overexpression of CD11b antigen and elevation of leukocyte derived plasma markers, namely cathepsin G and elastase. Finally all these blood cell activation leads to inflammation which is likely to play a significant role in the thrombotic risk of myeloproliferative neoplasms.
Keynote Forum
M Dahmani Fathallah
Arabian Gulf University, Bahrain
Keynote: Genomics, gene editing & biological drugs: The bolsters of the new medical paradigm
Time : 09:40-10:20
Biography:
M Dahmani Fathallah is a Professor of Molecular Biotechnology and International Expert in Health Biotechnology and Biopharmaceuticals. He has obtained a PhD in Molecular Biology & Immunology from the University of Paul Sabatier France and Oxford University, UK in 1985. He also holds a PhD in Molecular Genetics and also validated an e-learning MBA in Biotech Management from Boston University. He is a Former Postdoctoral Fellow and Senior Scholar at Harvard Medical School, Boston, USA. He has founded and directed for 12 years, an R&D group in health biotechnology, at the Institute Pasteur of Tunis. His field of expertise is in the molecular design, engineering and development of new bio drugs, biosimilars, subunit vaccines and antibodies. He is currently leading the Biotechnology program at the Pharmaceutical Technology Center of the Kayyali Chair at King Saud University, School of Pharmacy, Riyadh, KSA. He is the Senior Advisor for Technology Transfer at the Riyadh TechnoValley Inc., and King Saud University Office of Knowledge Exchange & Technology Transfer. He has published over 60 researches, review and pedagogic papers in peer reviewed international journals as well as 2 books and books chapters. He is a Member of several international scientific societies and Reviewers for more than 10 international biotechnology journals.
Abstract:
In the dawn of this new century, advances in our understanding of the intricate molecular mechanisms of human life in health and disease states are introducing a paradigm shift in medicine. Disruptive innovations in the way of diagnosis, prevention and therapy of most alienating diseases will be carried out are underway. In this lecture we will discuss three major technical developments in genomics, biological drugs design and gene editing, that are significantly reshaping the medical landscape. These developments are the results of the translation of a significant amount of scientific knowledge into medical practices. This knowledge was accumulated in the field of genetics and from the unraveling of the human genome, in biotechnology with genetic engineering and mass production of powerful biological products and in the discovery of a more accurate ways to edit genes. Thanks to the development of such approaches, we are shifting from the conventional use of the empirical 'one drug fits all' therapeutic practice to a novel type of personalized medical practice where rational companion genetic testing will be used to back biological drug clinical efficiency by identifying the most genetically qualified patient subgroup. Precision gene editing will correct all genetic alterations associated with diseases and gene therapy should become a safe and routine procedure. These technologies will definitely bolster medicine in the short term and hematological disorders will be at the forefront of the pathological conditions that will benefit from such technologies. The use of these new technologies is not free from ethical and economic issues that urgently need to be sorted out for this new paradigm to thrive.
- Hematology| Blood Disorders: Diagnosis and Treatment| Hematology Oncology
Location: Orly
Chair
M Dahmani Fathallah
Arabian Gulf University, Bahrain
Co-Chair
Natalia Neparidze
Yale School of Medicine, USA
Session Introduction
Igor Križaj
Jožef Stefan Institute, Slovenia
Title: Serine protease homolog from snake venom, a promising new anticoagulant lead molecule
Time : 12:10-12:35
Biography:
Igor Križaj completed his Doctoral studies at Jožef Stefan Institute in Ljubljana (JSIL) and at Imperial College in London. He completed his Post-doctorate studies at Institute Pasteur in Paris. He is Head of Department of Molecular and Biomedical Sciences at JSIL and full Professor of Biochemistry at University of Ljubljana. He has published more than 130 research papers in the SCI-journals. He has been serving as an Editorial Board Member at several scientific journals and as Secretary of the European Section of the International Society on Toxinology.
Abstract:
Most frequently used anticoagulant therapies may induce severe complications. To overcome these limitations, new anticoagulants have been intensively searched for. We report here the purification and characterization of a glycoprotein from the venom of the nose-horned viper (Vipera ammodytes), which significantly prolonged activated partial thromboplastin time in human plasma. Amino acid sequence of this protein (VaaSPH) revealed it as a serine protease possessing two mutations in its catalytic triad that renders it enzymatically inactive. Detailed analysis of the mechanism of blood coagulation inhibition by VaaSPH unveiled that the molecule inhibits the activity of tenase and prothrombinase complexes, with IC50 values of 142 nM and 134 nM, respectively. It was demonstrated that inhibition of the complexes formation was due to the binding of VaaSPH to blood coagulation factors VII, IX and X, to their activated forms and to FVa and FII. In addition, VaaSPH was also found to bind specifically to phosphatidylserine, a negatively charged phospholipid, which directed the assembly of the enzyme–cofactor complexes on membrane surface of platelets. Three-dimensional structure comparison of FVII, FIX, FX, FII and their respective activated forms suggested two areas on their surfaces, in proximity of their active sites, where VaaSPH binds. Such a proposal was also experimentally supported. As a potent non-enzymatic and coagulation factor active-site independent inhibitor of blood coagulation process, VaaSPH is unique and therefore, very interesting for a further characterization to design, based on its structure, a novel family of selective coagulation factor inhibitors of therapeutic relevance for anticoagulant therapy.
Natalia Neparidze
Yale School of Medicine, USA
Title: Whole body magnetic resonance imaging in newly diagnosed multiple myeloma: Influence on treatment decisions
Time : 12:35-13:00
Biography:
Natalia Neparidze completed her Medical Degree at Aieti Medical School in Tbilisi, Georgia in 2000. She completed her Post-doctoral Research Fellowship at Emory University, Northwestern University and at Yale University, followed by Internal Medicine Residency and Hematology/Medical Oncology Fellowship at Yale University. She is an Assistant Professor at Yale University, with the research focus on Multiple Myeloma, with specific interests in “Advanced imaging and tumor heterogeneity, as well as strategies for intensification of maintenance therapy in multiple myeloma”.
Abstract:
Advanced imaging modalities are being increasingly utilized for initial evaluation in patients with multiple myeloma. Whole body magnetic resonance imaging (WB-MRI) is far superior to standard metastatic bone survey (MBS), and may even outperform positron-emission tomography (PET). We performed both baseline MBS and WB-MRI on 15 myeloma patients prior to initiation of therapy. Multi-planar, multi-sequence MRI of the whole body was acquired without intravenous contrast. The imaging studies were evaluated to determine their respective merits for disease staging and their impact on treatment decisions. WB-MRI detected myeloma lesions in 33% of patients (5/15), whereas MBS identified lesions in only 6% (1/15). Overall, information obtained from WB-MRI significantly influenced the patient’s staging in 73% of patients (11/15), and directly impacted treatment decisions whether or not to begin induction therapy in 46% of patients (7/15). WB-MRI identified myeloma bone lesions, which otherwise would have been missed by standard bone survey in 27% of patients (4/15). Myeloma related bone lesions occurred predominantly in the axial skeleton, most commonly seen in cervical, thoracic, lumbar spine and pelvis. We conclude that WB-MRI at diagnosis provides valuable information on the extent and the stage of the disease, significantly influences treatment decisions and is worth to be incorporated in initial diagnostic evaluation of patients with multiple myeloma.
Lunch Break 13:05-14:00 @ Mediteraneo
Rouslan Kotchetkov
Royal Victoria Regional Heath Centre, Canada
Title: Characterization and management of synchronous dual hematological malignancies
Time : 14:00-14:25
Biography:
Rouslan Kotchetkov has completed his MD in 1994 at Minsk University, Belarus and PhD in 1998 at Frankfurt University, Germany. After re-training at Queens University, he acknowledged his MD degree in Ontario in 2007, followed by Post-gradual training in Internal Medicine at McMaster University, Adult Hematology at University of Toronto, and fellowship in Mature Lymphoproliferative Disorders and Lymphoma at Princess Margaret Cancer Center. Since July 2013, he is a staff Hematologist-Oncologist at Simcoe Muskoka Regional Cancer Program. He is an Assistant Professor of Medicine at University of Toronto. He has published over 50 papers and has 40 oral and 12 poster presentations at scientific conferences.
Abstract:
Characterization and management of patients with a synchronous dual hematological malignancy (SDHM) is not well described. In our database, we identified 41 patients with clonally unrelated SDHM, a prevalence of 1.35%, median age 75 years (23-90) and male predominance. 31.7% had concomitant solid cancers, suggesting increased susceptibility to SDHM or impaired immunity. Referrals from general practitioners were for a general diagnosis (65%) or for a non-specific symptom (35%). With referrals from specialists only asymptomatic secondary diagnoses were missed. SDHMs were diagnosed incidentally or because of discordance in clinical/laboratory findings. Three combinations of SDHMs were identified. In the myeloid+lymphoid group, concomitant MGUS was most frequent. Within the lymphoid+lymphoid group, SDHM combinations were random. There were only three myeloid+myeloid SDHMs. 70.7% required therapy for primary malignancy, 29.3% needed active surveillance. For a secondary diagnosis, 70.7% patients were actively monitored, and 29.3% needed treatment. At the completion of treatment for primary malignancy, 90% were either in remission/non-progressing disease or 10% progressed. Overall SDHM survival was 82.9% vs. 87.2% of control. Our management experience of SDHM is following: Have low threshold for intensive investigations if there are discordant data; patients with low-grade/low-acuity SDHM can be on active surveillance with early re-evaluation of both diseases if conditions change; if two malignancies require treatment, aim therapy at the more aggressive one; ABVD chemotherapy completely resolves cutaneous T-cell lymphoma lesions; cladribine has no effect on concomitant chronic myelomonocytic leukemia; ruxolitinib precipitates chronic lymphocytic leukemia; hydroxyurea decreases M-spikes in MGUS, regardless of type; azacitidine improves mast cell leukemia, bone marrow fibrosis, but has no effect on follicular lymphoma and; phlebotomized patients with polycythemia vera may develop profound anemia on chemotherapy, requiring holding phlebotomies, IV iron, erythropoietin-stimulating agents/red cell transfusions. Further studies of SDHM, exploring different cohorts and ethnicities, are needed.
Soad K Al Jaouni
King Abdulaziz University, KSA
Title: Hydroxyurea, an effective therapy to avoid splenectomy in sickle cell disease and thalassemia: Single institute experience in Saudi Arabia
Time : 14:25-14:50
Biography:
Soad K Al Jaouni is a Professor and Consultant of Hematology; Professor/Consultant of Pediatric Hematology/Oncology and Senior Researcher in Hematology department, Faculty of Medicine, King Abdulaziz University Hospital- a tertiary care medical center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. She received her certificate of Royal College of Physician and Surgeon in Medicine in 1989. She yearly participates in international and local conferences with more than 260 research and 74 publications. She is well known for her dedication, active role in research on Hereditary Blood Disease, Cancer Research. She has an active role in Public Education to minimize and control inherited blood diseases, environmental pollution and cancer prevention.
Abstract:
Background & Aim: Spleen plays an important part in the immune system which helps the body to fight against infection and has a major role in children. Splenectomy has been decline in hemoglobin disorders in recent years. Aim of this study is to assess the role of hydroxyurea and to eliminate the risk of splenectomy in sickle cell disease (SCD) and thalassemia at our medical center.
Methods: Total of 54 patients enrolled in the study from 2004 to 2016 at King Abdulaziz University Hospital, Faculty of Medicine and King Abdulaziz University, Saudi Arabia. 25 sickle cell disease (SCD), 17 thalassemia major (TM) were suboptimal transfusion dependents and hypersplenism, 12 thalassemia inter media (TI).
Results: Risk of splenectomy has been avoided in 24/25 SCD, 15/17 in TM and 12/12 in TI.
Conclusion: Hydroxyurea is an effective and safe therapy can eliminate risk of splenectomy in SCD and thalassemia. Recent studies and meta-analysis showed that hydroxyurea is safe and non-carcinogenic.
Antonella Bianchi
Università Campus Bio-Medico, Italy
Title: PD1-PDL1 axis in lymphoproliferative diseases: The pathologist’s point of view
Time : 14:50-15:15
Biography:
Antonella Bianchi completed her Graduation in Medicine and Surgery in 1991 and Post-graduate Diploma in Pathology at Catholic University of Rome in 1996. She is an Assistant at Pathology Unit of University Hospital Campus Bio Medico of Rome (Italy) and she is the referent for hematological pathology with numerous published papers in reputed journals. She attends national and international conferences and she is a member of two scientific societies (SIAPEC and FIL). She performs teaching and tutorial activity for the School of Medicine.
Abstract:
The PD1-PDL1 axis is one of the major mechanisms of immune escaping exerted by several cancer types in which up-regulation of PDL1 is observed. The success of checkpoint blockade therapy in the treatment of different solid tumor encouraged the research for similar results in the spectrum of lymphoproliferative diseases. Several clinical trials of PD1-PDL1 blockade have been conducted in hematologic malignancies, in particular, in Hodgkin lymphoma. In order to improve the therapeutic usefulness of this approach, several studies were performed to investigate and quantify the PD1-PDL1 expression levels by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue sections, in different B-cell and T-cell lymphoma entities and in classical Hodgkin lymphoma. As for other predictive biomarkers, reliable results are achieved by performing the staining in a standardized setting of pathology laboratory practice. Numerous critical issues are under evaluation to determine the reproducibility of PD1-PDL1 immunohistochemistry. The IHC labeling is sensitive to pre-analytical parameters (e.g. cold ischemia, the type and duration of fixation). Negative and positive control slides should be included in each staining run. An expert pathologist using a light microscope should assess the staining pattern, both in morphologically unequivocal tumor cells and in ineffective inflammatory infiltrating cells. The scoring may be achieved using 10-20x objectives and confirmed at 40x if needed. PDL1 expression should be semi-quantitatively evaluated in representative areas with the higher percentage of neoplastic cells while tumor areas with necrosis should be excluded. Cytological material usually does not allow correct evaluation of the cell stained with anti-PDL1 antibodies.
Osaro Erhabor
Usmanu Danfodiyo University, Nigeria
Title: Some iron parameters among transfusion-dependent subjects in Maiduguri, Nigeria: The case for provision of chelating agents in developing countries
Time : 12:55-13:20
Biography:
Osaro Erhabor is a Professor of Hematology, Transfusion Medicine and Laboratory of Total Quality Management. He is an Alumni of Rivers State University of Science and Technology, Nigeria, University of Greenwich in the United Kingdom and Francis Tuttle College of Technology in Oklahoma, USA. He is the Author of five scientific books. He has published more than 190 scientific papers in the field of Infectious Diseases, Hematology, Blood Transfusion Science and Total Quality Management. He is a member of the editorial board as well as an article Reviewer of several international scientific journals.
Abstract:
The spectrum of haemolytic disease of the new-born has changed over the last decade. With the implementation of rhesus D immunoprophylaxis, haemolytic disease due to ABO incompatibility and other alloantibodies has now emerged as major causes of this condition. In this present study, we investigated ABO and rhesus D blood group distribution and haemolytic disease among the new-born in Sokoto Specialist Hospital Nigeria. The study included a total of 79 samples each collected from mothers and neonates delivered in Sokoto Specialist Hospital. ABO and rhesus D blood group was determined on samples from the mothers and the neonates. Direct anti-globulin test (IgG and complements) was carried out on the samples from the neonates. ABO, rhesus D and direct anti-globulin (IgG and complements C3b and C3d) was carried out using the column agglutination technique (Ortho Diagnostics, USA). ABO blood group distribution indicated that a total of 44 mothers were of blood group O (55.7%), 22 were of blood group A (27.8%), 12 were of blood group B (15.2%) and one was AB (1.3%). Among the neonates, rhesus D positive has the highest frequency of 57 (72.2%) and rhesus D negative with a frequency of 22 (27.8%). Rhesus D group distribution among the mothers indicated that 74 mothers were rhesus D positive (93.7%) and only 5 were grouped as rhesus D negative (6.3%). Of the 79 neonates tested, 36 were of blood group O (45.6%), 21 were of blood group A (26.6%), 20 were of blood group B (25.3%), 2 were of blood group AB (2.5%). Haemolytic disease of the fetus and new-born (HDFN) status of the neonates indicated that four neonates were positive (5.1%). Two (2.5%) cases were ABO incompatibility-related while rhesus D related incompatibility accounted for two (2.5%). Among the four cases of HDFN, two cases (2.5%) of due to the effects of complements while two (2.5%) were due to IgG antibodies. Findings from this study indicates that haemolytic disease of the fetus and newborn due to ABO and rhesus D incompatibility between mothers and their babies is prevalent in Sokoto, North Western Nigeria. We recommend that universal antenatal screening in all pregnant women can be initiated. A close follow up throughout pregnancy is required to detect the presence of irregular antibodies. There is need to consider universal antenatal screening and provision of prophylactic anti-D prophylaxis to prevent rhesus D negative pregnant women from producing immune anti-D following potentially sensitizing events and HDFN in subsequent pregnancies.
Biography:
Aisha Patel has completed her BSc (Honours) in Life Sciences and Psychology at Queen’s University of Canada and MBBS at Imperial College, London. She is currently a Doctor in Emergency department at Gloucester Royal Hospital, UK. She has keen interest in Oncology.
Abstract:
This study presents a case report of a 54 year old female recently diagnosed with pancreatic cancer. Sudden onset of right leg pain with subsequent diagnosis of acute limb ischaemia and death two days later from septicaemia was observed. Venous thrombosis is a common complication of cancer, especally pancreatic cancer. However, the research available on arterial thrombosis as a complication of pancreatic cancer is sparse and it is hoped that there will be a greater vigilance for both venous and arterial thrombus as this is a very serious complication and can be difficult to manage. This case report includes in depth look at the research available on arterial thrombosis in pancreatic cancer.
Elvira MaliÄev
Blood Transfusion Centre of Slovenia, Slovenia
Title: A flow cytometric assay for the confirmation of heparin-induced thrombocytopenia (HIT)
Time : 16:25-16:50
Biography:
Elvira MaliÄev is an Assistant Professor at University of Ljubljana and Head of Laboratory for flow cytometry at Blood Transfusion Centre of Slovenia, where she works on Platelets, Erythrocytes and Stem cells. Her main research interests include Mesenchymal and Hematopoietic Stem Cell Biology.
Abstract:
Heparin-induced thrombocytopenia (HIT) is induced by the antibodies against neoepitopes in complexes of heparin with a platelet factor 4 (PF4). Anti-heparin/PF4 antibodies are capable of platelet activation by cross-linking to platelet Fcγ receptor IIa. Patients with HIT usually have thrombocytopenia between 5-10 days after heparin therapy has started and are at an increased risk of developing venous or/and arterial thromboses. However, not all patients with detected anti-heparin/PF4 antibodies go on to develop HIT. The diagnosis is a challenge and requires an exact analysis of the clinical and laboratory parameters. Laboratory testing includes both serological and functional assays. Enzyme immunoassays (ELISA) are most often used for detecting the presence or absence of anti-heparin/PF4 antibodies in a patient`s serum. ELISA is highly sensitive but has a low specificity because it detects both platelet activating and platelet non-activating anti-heparin/PF4 antibodies. To confirm the presence of pathogenic platelet activating antibodies, one of the functional assays has to be done. Functional assays generally require technical expertise, special equipment and the use of fresh donor platelets; therefore, laboratories rarely perform them. The serotonin release assay (SRA) and the heparin-induced platelet activation assay (HIPA) are the most well-known functional assays. Another possibility to confirm HIT could be the use of flow cytometry. We have introduced the functional flow cytometric assay for routine testing of suspect HIT patients. The assay is based on detection of CD61 antigens, and CD62P molecules (P-selectins), expressed on platelet surface after α-granule exocytosis. Each sample (patient’s serum, positive and negative control) is tested against fresh platelets obtained from four healthy donors. The assay is positive when at least two of four donor platelets are activated at a low concentration of heparin, and at the same time the parallel reaction is inhibited in the presence of excess heparin.
Salem Khalil
King Faisal Specialist Hospital and Research Centre, Saudi Arabia
Title: Paroxysmal nocturnal hemoglobinuria: A multicenter study from Saudi Arabia
Biography:
Salem Khalil completed his MBBS at King Saud University Riyadh in 1984; fellowship of the Royal College of Pathologists of Australasia, Australia in 1992 and; fellowship in Molecular Hematopathology at MD Anderson Cancer Center, Huston, Texas, USA.
Abstract:
Background & Aim: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic stem cell disorder, characterized by the deficiency of glycophosphatidylinositol (GPI) that anchors proteins in cell membranes. PNH is manifested variously with hemoglobinuria, thrombosis, or bone marrow failure. This multi-central retrospective study was aimed at assessing the incidence and characteristics of patients diagnosed with PNH in Saudi Arabia.
Methods: Patients referred for PNH diagnosis at King Faisal Specialist Hospital and Research Centre, Riyadh during the 3-year period (2007-2009) and the 2-year period (2012-2013), also at King Faisal Specialist Hospital and Research Centre, Jeddah, King Abdulaziz Medical City (NG), Riyadh, King Abdulaziz Medical City (NG), Jeddah data during the last year 2014, were included in the analysis. Peripheral blood samples were used for multi-parametric flow cytometry analysis based on fluorescent inactive aerolysin (FLAER), and the markers, CD235a and CD59 on red blood cells (RBCs), and CD14, CD45, CD64, CD24, and CD15 on white blood cells (WBCs) exclusively monocytes and granulocytes. Univariate analysis of the disease characteristics was performed.
Results: Of the 843 samples submitted for PNH screening, 40 were positive (4.7%). Of the 40 patients analyzed, 22 patients (55%) presented with aplastic anemia, 4 patients (10%) with pancytopenia, and 3 patients with thrombosis (7.5%) one with Budd-Chiari syndrome and 2 with portal vein thrombosis. Hemolytic anemia represented 5% (2 patients) of all cases. Other positive cases were presented with unrelated diseases such as immune thrombocytopenic purpura (ITP) in 2 cases (5%) and non-specific diagnosis in the rest. All samples showed type II and III GPI-deficient clones with a median clone size of 12 (range, 0.04%-85%) in the RBCs, and 56 (range, 1%-100%) in WBCs (monocytes and granulocytes).
Conclusions: This study confirms the rarity of PNH and its predominant presentation as aplastic anemia or thrombosis in a Saudi Arabian population, similar to the worldwide incidence.
Yulia Einav
Holon Institute of Technology, Israel
Title: Thalassemia minor diagnostics by a computational method
Biography:
Yulia Einav completed her PhD at Tel Aviv University. She works at Holon Institute of Technology (Israel). Currently, she has published 20 papers and book chapters in reputed journals and textbooks. In addition, she serves as Dean of Students of Holon Institute.
Abstract:
Thalassemia minor (TM) condition is often unrecognized and undiagnosed due to technical or cost issues. The benefit of early diagnosis of TM patients is a prevention of unnecessary treatments and costly tests and a referral to a genetic counseling. The use of complete blood count (CBC) parameters to screen for TM condition has been proposed in the past decade and performed with variable success. Here, we propose to use artificial neural networks (ANNs), which are successfully applied to various fields of medicine and beyond to find patterns in ambiguous data. ANN model comprises of an interconnected group of artificial neurons that learn through experience. Like a biological neuron network, the ANN is designed to obtain an input, analyze the data and supply the output, which in most cases would be some prediction about the patterns and behavior of the studied system. In this study, we created more than 1,500 ANNs and selected the networks that gave highest accuracy results. Input consisted of six CBC parameters: MCV, RBC, RDW, HB, MCH, and platelet count. This broad approach allowed us to provide a differential diagnosis for TM patients with specificity above 0.96 and sensitivity of 1. In addition, we show that in our method MCV, RBC, and RDW counts are of greater importance than the other three parameters. The low cost of our model makes it important worldwide and especially in the developing countries. Moreover, similar ANN-based method can be applied for the screening of other diseases that change CBC parameters.
Chintan Shah
University of Florida, USA
Title: Incidence, natural history and outcome of targeted therapy-induced cardiotoxicity in hematologic malignancy (HM) patients
Time : Chintan Shah
Biography:
Chintan Shah, is working as a Clinical Assistant Professor at the University of Florida, Florida, USA. After being born and raised in India, he moved to the United States in 2011. He completed his graduate training in the field of internal medicine from the Western Michigan University School of Medicine and is currently working as an internist. He has done quite a few presentations at the national and international conferences and has published in peer-reviewed journals. His goal is to achieve clinical excellence, provide compassionate care to patients and pursue a carrier in the field of Hematology and Oncology.
Abstract:
Introduction & Aim: Unanticipated cardiotoxicity is now identified as a significant clinical problem associated with new anti-cancer targeted agents. Risk factors and natural history are still poorly understood and are the main aim of this study.
Methods: We used 114 diagnosis codes for HM and 17 for cardiac diseases in order to identify patients in our electronic medical records (EPIC) over 10-year period. Cardiotoxicity was defined by left ventricular ejection fraction (LVEF) of <50%, arrhythmias, or ischemic cardiovascular event that occurred after initiation of the drug of interest. The targeted agents of interest include tyrosine kinase inhibitors (TKIs), proteasome inhibitors, monoclonal antibodies, hypomethylating agents, and immunomodulatory agents. Multivariable logistic regression, Kaplan-Meier analysis and log-rank test were used for statistical calculations.
Results: Of 820 patients with both HM and cardiac diagnosis, 29 patients (3.5%) developed cardiotoxicity after initiation of targeted therapies. We selected 70 matched controls based on type of targeted therapy. In the study group, the median time from exposure to cardiac event was 120 days (interquartile range, 30-180). Multiple variables, including conventional risk factors for heart disease, were not different between the two groups except prior history of DVT/PE (P=0.011), and Karnofsky score of ≥80% (P=0.005). With median follow-up of 27 months, two patients in the study group died of cardiac causes. Repeat echocardiograms showed stable/improved LVEF in 23 patients. There was a trend towards worse OS in the study group (P=0.071).
Conclusions: About 3.5% of patients with HM experienced unanticipated cardiotoxicity due to targeted anti-cancer agents with related mortality of 6.8%. Most patients do well with stable compensated cardiac function. Risk of cardiotoxicity was significantly higher in patients with known history of DVT/PE. Future studies of possible underlying genetic predisposition will be of great importance.
- Blood Disorders|Hematology and Its Various Aspects| Case Reports
Location: Orly
Chair
John Batchelor
Central Manchester Foundation Trust, UK
Co-Chair
Rouslan Kotchetkov
Royal Victoria Regional Heath Centre, Canada
Session Introduction
Leonard Tan
Singapore General Hospital, Singapore
Title: Dynamic apperception of the sick germinal centre insights gleaned by follow-up of earlypattern angioimmunoblastic T-cell lymphoma and its immune-architectural comparison with reactive lymphoid hyperplasia
Time : 10:20-10:45
Biography:
Leonard Tan completed his Graduation at National University of Singapore, Faculty of Medicine in 1989 and completed his Degree in Histopathology at Royal College of Pathologists in London in 1999. He was a visiting Research Fellow in Hematopathology at Weill Medical College of Cornell University. He is now a Senior Consultant, Histopathologist at Singapore General Hospital, and has been Chief Diagnostic Pathologist of Lymphoma Work Group at National Cancer Centre, Singapore since 2006. His main research interest is in “Lymphoid immuno-architecture, particularly of peripheral T-cell lymphomas with large B-cells”.
Abstract:
Angioimmunoblastic T-cell lymphoma (AITL) ranges widely in clinical tempo, on the one hand mimicking an immune reaction and on the other, being as aggressive as any T-cell lymphoma. This is reflected by its varied histological pattern, designated one through three, with hyperplastic, regressed or effaced germinal centers (GCs), respectively. Having recently being clinched as a neoplasm of follicular helper-T (TFH) cells by gene expression profiling, it has now become pertinent and also feasible to distinguish the changes of pattern 1 AITL from reactive lymphoid hyperplasia by immune architectural analysis. In population studies, the life cycle of any organism can be inferred by photographing individuals of various ages, juxtaposing the most similar photographs to form a spectrum, then blending or morphing them to create meta-animation, so as to impart dynamic apperception of the organism’s life cycle. This would effectively translate a cross-section of the population into a representation of an individual organism’s entire lifespan, circumventing barriers of limited contact time and interference with natural history. In the same way, immunohistological sections, which are formalin-fixed, paraffin-embedded snapshots-in-time of living tissue can be interrogated with multiple photomicrographs of the GCs in early-pattern AITL, juxtaposed in similar gradation, and then shown in sequence to produce a meta-movie of the aberrant outward migration of neoplastic TFH cells, as though being filmed in real-time through a microscope trained on live cells. Hence, this presentation aims to demonstrate a phenomenon hitherto unexpressed through conventional histopathology, coupled with clinical and scientific observations that support this dynamic interpretation.
Soad K Al Jaouni
King Abdulaziz University, KSA
Title: Nigella sativa and honey improves quality of life in Kostmann syndrome: Case report
Time : 10:45-11:10
Biography:
Soad K Al Jaouni is a Professor and Consultant of Hematology; Professor/Consultant of Pediatric Hematology/Oncology and Senior Researcher in Hematology department, Faculty of Medicine, King Abdulaziz University Hospital- a tertiary care medical center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. She received her certificate of Royal College of Physician and Surgeon in Medicine in 1989. She yearly participates in international and local conferences with more than 260 research and 74 publications. She is well known for her dedication, active role in research on Hereditary Blood Disease, Cancer Research. She has an active role in Public Education to minimize and control inherited blood diseases, environmental pollution and cancer prevention.
Abstract:
Congenital agranulocytosis (Kostmann syndrome) is associated with severe neutropenia, recurrent infections resulting with the demise of the patient at an earlier age. Aim of this study is to evaluate applying supplementation of Nigella sativa and honey for Kostmann syndrome. 14 years old male patient diagnosed during the first few months of life as Kostmann syndrome by frequent admission for bacterial infection and peripheral blood films with automated neutrophil count (ANC) range from 0.1-0.3x10(9)/L, bone marrow aspiration confirming the diagnosis of Kostmann syndrome, patient have positive consanguinity and family history for a similar condition, elder brother died of sepsis during the first year of life. Patient has history of frequent hospital admissions for infections, starting from 2nd day of life, including 26 inpatient admissions from 2002 to 2004 with positive blood and urine cultures. Patient received courses of filgrastim recombinant granulocyte colony-stimulating factor (G-CSF) with reported cataract after few months later. Patient was started on regular daily intake of Nigella sativa and honey from 2005; he showed dramatic improvement in several days like aspects as his hospital admissions with no single admission for infection from 2005 till 2016. Family reports marked improvement in patient quality of life with better regular school attendance after subsidence of infections. Patient was monitored regularly in hematology clinic. We conclude Nigella sativa and honey may not affect the automated neutrophil count but may improve the immune system and the quality of life in Kostmann syndrome. More research is needed to find the relation between Nigella sativa supplementation and immune modulation
Mingzhi Zhang
First Affiliated Hospital of Zhengzhou University, China
Title: Progress in diagnosis and treatment of advanced NK/T cell lymphoma
Biography:
Mingzhi Zhang completed his PhD at Zhengzhou University Medical School. He is the Director of Lymphoma Diagnosis and Treatment Center in Henan Province and Department of Oncology, The First Affiliated Hospital of Zhengzhou University. He has published more than 30 papers in reputed journals and achieved honors and awards on Lymphoma Research in China.
Abstract:
Natural killer/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin’s lymphoma, which has a higher incidence in East-Asia compared with United States and Europe. This tumor is characterized by highly aggressive nature, rapid progression and poor survival. However, optimal treatment strategies for advanced NKTCL have not been defined. Traditional CHOP and CHOP-like regiments usually provide poor clinical outcomes. Recently, L-asparaginase (L-Asp) based regimen including dexamethasone, methotrexate, ifosfamide, L-Asp and etoposide (SMILE) has been devised and showed a relatively improved efficacy, but at the same time, severe hematologic toxicity were seen. We formulated a novel pegaspargase based chemotherapy regimen: dexamethasone, cisplatin, gemcitabline, pegaspargase (DDGP) and performed clinical trial (No. NCT01501149). Patients were newly diagnosed in stage III-IV and had performance scores in 0-2. Six cycles of DDGP or SMILE chemotherapy were randomly assigned to them. In conclusion,DDGP chemotherapy resulted in significant improvement in one-year PFS (86% versus 38%, P=0.006), two-year OS (74% versus 45%, P=0.027) and better tolerability compared with SMILE chemotherapy. We also discussed and elucidated the mechanisms concerned with the better effect of DDGP on DNA damage, nucleic acid metabolism, and ATP-binding cassette transporters-dependent multidrug resistance. In addition, we are making great efforts to explore new approaches including hematopoietic stem cell transplantation with a unique induction chemotherapy and application of PD-1 immune checkpoint inhibitor, which greatly benefit the patients after chemotherapy failure.
Jean-Francois Schved
Montpellier University Hospital, France
Title: Management of cardiovascular disease in hemophilia
Time : 10:20-10:45
Biography:
Jean-François Schved is a Doctor and Professor of Hematology at Faculty of Medicine, Montpellier University. His main theme of study and research is Haemostasis, especially hemorrhagic disease and hemophilia. His other research work focused on “Thrombotic disease and the risk factors for thrombosis”. His team has also conducted important scientific work on red blood cells and genetic iron overload. He published, in collaboration with various units of research or hospital services, more than 200 scientific articles in international journals and participated in writing of many medical books. He reviews frequently manuscripts for major journals.
Abstract:
With the well-known increase of the life expectancy in patients with hemophilia (PWH), patients are faced with age-related comorbidities. Thus, over the last few years, hematologists appear to be witnessing an increase in the frequency of cardiovascular diseases, mainly ischemic cardiopathies or atrial fibrillation. These diseases raise major difficulties in PWH while the recommended treatments rely on antiplatelet agents and anticoagulants. Anticoagulants and antiplatelet treatments increase the risk of bleeding in hemophiliacs and cardiovascular interventions commonly complicate bleeding. To minimize these risks, the clotting factor deficiency needs to be adapted. To get more information on the possibility of treatment, we launched an observational study called COCHE (comorbidity of cardiovascular origin in hemophilia) including PWH treated for atrial fibrillation or ischemic cardiopathies. Some patients underwent endovascular procedures, the minimal follow-up being two years. From these data, it appears that anti-platelet agents can be used with caution and under certain conditions in most hemophiliacs. Invasive cardiovascular interventions are possible and anticoagulants treatments or dual anti-platelet therapy can often be used. In all cases, close collaboration between the cardiologist and hematologist is necessary to offer the patient an optimum treatment.
Ayesha Junaid
Shifa International Hospital, Pakistan
Title: Implementing NAT & universal parasitic screening for blood donors: Maximizing donor surveillance
Time : 12:30-12:55
Biography:
Ayesha Junaid completed her Graduation at King Edward Medical University, Lahore. She is a member of Clinical Pathology (2000) and Fellow of Clinical Hematology (2002) at College of Physicians & Surgeons, Pakistan. She has completed her training in Cytogenetics & FISH technique at UCLA, USA (2008). She is a Consultant Hematologist and In-charge of Blood Transfusion Services & Hematology department at Tertiary Care Hospital, Islamabad. She also works as a Transplant Consultant mainly involved in Hematological Malignancies. She is presently working as Professor of Pathology at Shifa College of Medicine, Islamabad. She is an elected syndicate member of Shifa Tameer-e Millat University, Islamabad.
Abstract:
Introduction: Selection of an uninfected donor is of extreme importance in enhancing transfusion safety. Presence of week’s long window period of fatal viral infections in serologically screened donors provides an ever existing possibility of fatal disease transmission through transfusion. We introduced nucleic acid amplification testing for viral screening and also scanned donors for two common endemic parasitic infections, Plasmodium and Treponema pallidum. Our institute provides 500 bedded tertiary care facilities with around 15,000 blood donors walking in annually to meet transfusion demand for a varied mix of oncology, dialysis, obstetric, pediatric, surgical and critical care patients. Malaria screening was added as our country falls in malaria endemic zone, while syphilis screening is lately added to prevent STD transmission.
Aim: Aim of this study is to minimize transfusion transmissibility of viral and parasitic infections to critical in-patients.
Methods: We tested 6,411 sero-negative donors (out of 6588 total donors) on NAT for HBV, HCV & HIV viruses in a period of six months (July-December 2015) using a minipool of six donors. Malaria screening was performed on 6588 donors using rapid testing based on species specific plasmodium LDH detection in human blood. 296 donor samples were screened for syphilis using qualitative electrochemiluminescence immunoassay.
Results: Five donors were found NAT positive for HBV out of a total of 6,411, saving 20 possible HBV transmissions through transfusion. Two donors out of 6588 were positive for Plasmodium vivax. Two donors out of 296 were positive for syphilis. Improved screening saved 36 possible infectious disease transmissions through transfusion over a period of six months.
Conclusion: Donor screening plays a vital role in improving transfusion practice. Hemovigilance activity upgrading and standardizing screening practices should be part of our vision to prevent infectious disease spread. Our next mission is to screen donors for dengue infection as the disease has lately shown marked increase in incidence in our country.
M Dahmani Fathallah
Arabian Gulf University, Bahrain
Title: A novel bispecific recombinant biological agent modulating inflammation’s early cellular events
Time : 12:55-13:20
Biography:
Abstract:
Multivalent and multifunctional bioactive molecules offer the promise of more effective therapeutics. In this work, we present selegrin, a new bispecific molecule that prevents the interaction of leukocytes circulating in the blood vessels with the endothelial barrier cells and could modulate the over flux of activated PMN to inflamed tissues. Prior to the development of selegrin, we have demonstrated using a rat model of skeletal muscle injury, that a recombinant form of the beta 2 integrin alpha chain CD11b, A or I domain prevents muscle inflammatory injury by transiently preventing leukocyte transmigration through the vascular endothelial cell barrier. Selegrin molecular design consisted in combining the CD11b A domain with the L selectin CD62, lectin-like domain in a single 52KDa fusion protein. Recombinant selegrin was produced in CHO cells under two structural forms, a linear and an IgG-like structure. Both form exhibited specific biological activity in real time of flow in physiological and inflammatory states using the ex vivo real-time imaging of leukocyte adhesion to the vascular endothelium of Sprague Dawley rats carotid arteries and HUVEC cell layers. Indeed, under inflammatory conditions, selegrin showed a significant inhibition of leukocytes tethering, rolling and adhesion to vascular endothelial cells. In addition, the transcription of IL6, ICAM1, VCAM1 and MCP1 gene and the expression of the corresponding proteins by respectively RT-PCR and immune fluorescence using specific Mabs, were significantly down regulated in endothelial cells treated with TNFa and in presence of selegrin. This delineates the underlying causes of the biological activity displayed by selegrin. This work demonstrated that selegrin exerts inhibitory effects on human leukocytes interaction with vascular endothelium cells under flow in physiological and inflammatory conditions. The data provide strong mechanistic information behind the anti-inflammatory properties of selegrin and are translatable in preclinical trial.
Sally Saad Mandour Esawy
National Liver Institute, Menoufia University, Egypt
Title: The diagnostic value of serum squamous cell carcinoma antigen (SCCA) for prediction of HCC patients
Time : 14:20-14:45
Biography:
Sally Saad Mandour Esawy completed his Master’s degree at Menoufia University. She is an Assistant Lecuturer in Clinical Pathology department at National Liver Institute, Menoufia University.
Abstract:
Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and shows a growing incidence worldwide related to the increased prevalence of the various risk factors of chronic liver diseases, such as hepatitis infection with hepatitis C and B viruses. Each year hepatocellular carcinoma is diagnosed in more than half a million people worldwide. Therefore, prompt diagnosis of HCC is imperative.
Aim: Aim of this study is to determine the efficacy of serum squamous cell carcinoma antigen (SCCA) in comparison to alpha-fetoprotein in the detection of hepatocellular carcinoma.
Methods: This study was carried out in Clinical Pathology department, Faculty of Medicine at National Liver Institute, Menoufia University all over the period from June 2012 to November 2013. The study included 30 patients with liver cirrhosis and 30 patients with HCC in addition to 17 unrelated healthy adult subjects with matched age and gender were included as controls. Serum alpha fetoprotein (AFP) and serum squamous cell carcinoma antigen level were estimated by enzyme linked immunosorbent assay.
Results: Although SCCA has more sensitivity than AFP in detection of HCC, AFP remains a relatively good diagnostic marker for HCC with high specificity.
Conclusion: AFP is a relatively good diagnostic test for cirrhosis with high specificity. Moreover combination of the two markers may improve the sensitivity making them combined a perfect screening tests for prediction of HCC
Osaro Erhabor
Usmanu Danfodiyo University, Nigeria
Title: Some iron parameters among transfusion-dependent subjects in Maiduguri, Nigeria: The case for provision of chelating agents in developing countries
Time : 14:45-15:10
Biography:
Osaro Erhabor is a Professor of Hematology, Transfusion Medicine and Laboratory of Total Quality Management. He is an Alumni of Rivers State University of Science and Technology, Nigeria, University of Greenwich in the United Kingdom and Francis Tuttle College of Technology in Oklahoma, USA. He is the Author of five scientific books. He has published more than 190 scientific papers in the field of Infectious Diseases, Hematology, Blood Transfusion Science and Total Quality Management. He is a member of the editorial board as well as an article Reviewer of several international scientific journals.
Abstract:
Conditions associated with refractory anemia require repeated blood transfusion. Despite the benefits of red cell transfusion, it is associated with complications including iron overload. The aim of this study was to determine some serum iron parameters, antioxidant vitamins and micronutrients levels among transfusion-dependent subjects. The study included 101 transfusion-dependent subjects and 50 apparently healthy controls that had no history of blood transfusion. Some iron parameters such as ferritin, serum iron and percentage transferrin saturation were significantly higher among the transfusion-dependent subjects (p=0.000) compared to controls. There was no correlation observed between ferritin and C-reactive protein (r=0.059, p=0.558). This study showed a significant decrease in HB, PCV, RBC, MCV, MCH and increase in platelet and white cell count among the subjects compared to the control (p<0.05). Vitamin A, B5, E and copper were significantly lower among the subjects compared to the control participants (p<0.05). There was no correlation between ferritin and vitamin A, B5, E and copper among the study subjects (p>0.05). Similarly, there was no significant correlation between the ferritin and zinc levels among the study subjects (p>0.014). There was a significant elevation in the serum iron parameters and simultaneous decrease in the antioxidant vitamins and micronutrients levels among the transfusion-dependent subjects. There may be need to routinely provide iron chelating treatment and supplementation of vitamin A, B5 and E for transfusion-dependent subjects in the area to obviate the possible negative effect of iron overload among the subjects.
Osaro Erhabor
Usmanu Danfodiyo University, Nigeria
Title: Some iron parameters among transfusion-dependent subjects in Maiduguri, Nigeria: The case for provision of chelating agents in developing countries
Biography:
Osaro Erhabor is a Professor of Hematology, Transfusion Medicine and Laboratory of Total Quality Management. He is an Alumni of Rivers State University of Science and Technology, Nigeria, University of Greenwich in the United Kingdom and Francis Tuttle College of Technology in Oklahoma, USA. He is the Author of five scientific books. He has published more than 190 scientific papers in the field of Infectious Diseases, Hematology, Blood Transfusion Science and Total Quality Management. He is a member of the editorial board as well as an article Reviewer of several international scientific journals.
Abstract:
Conditions associated with refractory anemia require repeated blood transfusion. Despite the benefits of red cell transfusion, it is associated with complications including iron overload. The aim of this study was to determine some serum iron parameters, antioxidant vitamins and micronutrients levels among transfusion-dependent subjects. The study included 101 transfusion-dependent subjects and 50 apparently healthy controls that had no history of blood transfusion. Some iron parameters such as ferritin, serum iron and percentage transferrin saturation were significantly higher among the transfusion-dependent subjects (p=0.000) compared to controls. There was no correlation observed between ferritin and C-reactive protein (r=0.059, p=0.558). This study showed a significant decrease in HB, PCV, RBC, MCV, MCH and increase in platelet and white cell count among the subjects compared to the control (p<0.05). Vitamin A, B5, E and copper were significantly lower among the subjects compared to the control participants (p<0.05). There was no correlation between ferritin and vitamin A, B5, E and copper among the study subjects (p>0.05). Similarly, there was no significant correlation between the ferritin and zinc levels among the study subjects (p>0.014). There was a significant elevation in the serum iron parameters and simultaneous decrease in the antioxidant vitamins and micronutrients levels among the transfusion-dependent subjects. There may be need to routinely provide iron chelating treatment and supplementation of vitamin A, B5 and E for transfusion-dependent subjects in the area to obviate the possible negative effect of iron overload among the subjects.
Albara Abdulfatah Mohammed
University of Khartoum, Sudan
Title: Assessment of coagulation profile, fibrinogen, protein C, protein S, antithrombin, and vitamin K levels among Sudanese neonates with proven sepsis in Omdurman Maternity Hospital, Sudan
Time : 15:10-15:35
Biography:
Albara Abdulfatah Mohammed has completed his PhD at University of Khartoum, Sudan; BSc and MSc at University of Medical Sciences and Technology. He is the Coordinator of Medical Laboratories Sciences Program at Alfajr College. His research interest is in Hemostasis.
Abstract:
Aim: Neonatal sepsis is lethal disease represents one of the most common causes of neonatal morbidity and mortality worldwide. Aim of this study is to assess platelets count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, protein C, protein S, antithrombin (AT) and vitamin K (VK) in Sudanese septic neonates and compare them with healthy neonates in order to study hemostatic alteration among septic neonates.
Methods: Prospective study was conducted in Omdurman Maternity Hospital in the period June 2013 to April 2015 on total of 100 samples divided into case and control group (50 for each). Blood culture was done routinely for all neonates with suspected sepsis; the first 50 neonates with a positive culture were taken as case group. Platelets were counted by cell counter haematology analyzer Sysmex KX-21. PT, APTT, TT, fibrinogen, PC and PS were assessed by clotting procedure via coagulometer Stago Start four. AT assessed spectrophotometrically by turbidimetric method via chemistry analyzer Mindray BA-88A. VK assessed by the Schmiatzu.10 ADVP. Data were tabulated; means were compared and analyzed by SPSS20 via one sample t test.
Results: In case group, 17 neonates underwent early onset sepsis (0-7 days) and 33 late onsets (7-28 days). In the outcome, 10 neonates were died. Means of platelets count, PT, APTT, TT, fibrinogen, PC, PS, AT and VK were 60,289 c/mm3, 16.6 s, 47.8 s, 18.6 s, 482.2 mg/dl, 34.4%, 33.4%, 183.9 mg/ml and 0.86 ng/ml; and 212,030 c/mm3, 13.9 s, 37.5 s, 20.6 s, 393.7 mg/dl, 36.8%, 34.7%, 221.5 mg/ml and 1.23 ng/ml for case and control respectively.
Conclusions: Platelets count significantly decreased, PT and APTT significantly prolonged, TT significantly shorted, fibrinogen significantly increased and AT significantly decreased in neonatal sepsis. APTT and PC showed significant correlation with outcome, so both can predict early mortality, PT and TT showed significant correlation with early sepsis.
Salem Khalil
King Faisal Specialist Hospital and Research Centre, Saudi Arabia
Title: Mutational analysis in hematological diseases
Time : 15:35-16:00
Biography:
Salem Khalil completed his MBBS at King Saud University Riyadh in 1984; fellowship of the Royal College of Pathologists of Australasia, Australia in 1992 and; fellowship in Molecular Hematopathology at MD Anderson Cancer Center, Huston, Texas, USA.
Abstract:
Background & Aim: Mutation analysis testing and targeting selected regions of multiple genes to facilitate diagnosis, classification and selection of therapy in patients with hematological diseases including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and beta thalassemia was reviewed.
Method: Genetic examinations were carried out by polymerase chain reaction using specific primers to amplify regions of interest. The amplified sequences were then determined by direct sequencing (Sanger sequencing) and quantitative real time PCR.
Results & Discussion: This study analyzed JAK2 mutations (exons 12–15) in 1811 patients tested between 2010 and 2013. 271 patients (16%) were positive for JAK2 mutations with median patient age of 54 years. In agreement with previous reports, 262 patients (96.7%) were positive for the JAK2 p.V617F mutation. Non-p.V617F JAK2 mutations were detected in the remaining nine (3.3%) patients. 87 patients (84%) were diagnosed with MPN, 40.2% with PV, 25.2% with ET, 12.6% with MF, 19.5% with unclassifiable MPN and 2.2% with CML. A variety of AML-specific mutations were screened in bone marrow samples of 100 adult and pediatric AML patients diagnosed between 2012–2014 showed 45% positivity for different kind of gene mutations. However, the frequency of these different mutations in AML is lower in our population compared to previously published studies from different international centers. In a total of 123 CML patients analyzed, 25 (20%) were positive for 11 different mutations across the ABL1 kinase domain mutations (11 patients had T315I, three patients with Y253H, two patients with E255K, and two more patients with F317L). 19 different mutations of the HBB gene were identiï¬ed in all detectable cases (103 patients). Among these mutations c.315+1 G>A, c.118C>T and c.92+5 G>C were detected in majority of cases (66%) with five novel mutations (c.410 G>A, c.-151C>T, c.68_74delAAGTTGG, c.316-3C>A, and c.-31 C>T) that are first time reported in Saudi population.
Conclusions: The results of this study underscore the importance of screening for genetic mutations in the initial evaluation of patients with suspected MPNs and AMLs or during a workup for relapse and TKI therapy resistance.
Kamran Mansouri
Kermanshah University of Medical Sciences, Iran
Title: L-arginine/5-fu combination preferentially rescues normal cells from apoptosis and not cancer cells
Biography:
Kamran Mansouri completed his PhD at Tehran University of Medical Sciences, Iran. He is the Head of Department of Molecular Medicine at Kermanshah University of Medical Sciences, Iran. He has published more than 50 papers in reputed journals.
Abstract:
Aim: This study aims to investigate L-arginine, nitric oxide (NO) precursor, in combination with 5-fluorouracil (5-FU) decreases 5-FU adverse effects on normal cells but not cancer cells which is among important chemotherapy goals especially during pregnancy.
Methods: The human umbilical vein endothelial cells (HUVECs) and human breast cancer cell line (BT-20) were treated with L-arginine/5-FU to study their effect on cell survival, NO concentration, and glycolytic activity. Moreover, using molecular docking study, L-arginine effect on glycolysis enzymes activity was evaluated. L-arginine/5-FU effect on angiogenesis was also assessed in vivo and in vitro. Furthermore, L-arginine effect on 5-FU toxicity was assessed by measuring embryo weight. Real-time PCR and zymography were used to evaluate VEGF and MMP2, 9 expression and enzyme activities, respectively.
Results: L-arginine/5-FU treatment increased cell survival in HUVECs but induced cell death in BT-20. NO concentration in both cell lines was increased. An inhibitory effect of L-arginine on glycolysis enzyme, human glucokinase (HG) was affirmed through molecular docking study and further supported by glycolysis experiment showing glucose and lactate levels decrease in cancer cells but not in normal cells. Angiogenesis induction in HUVECs was confirmed through VEGF and MMP-2, 9 up-regulated gene expressions and increased MMP-2, 9 activities but a down-regulation in BT-20 treated with both drugs alone and in combination. Furthermore, increase in vivo angiogenesis and decrease embryo cytotoxicity was observed.
Conclusion: Altogether, findings speculate that L-arginine inhibits cell death induced by 5-FU in normal cells by attenuating the adverse effects of 5-FU, while it doesn’t do so in cancer cells (BT-20).