FACULTY • Sabri Kemahlı (Yeditepe University Faculty of Medicine, Istanbul, Turkey) • Güner Hayri Özsan (Dokuz Eylül University Faculty of Medicine, İzmir, Turkey) • Emin Kansu (Turkey) Hacettepe University Cancer Institute and Department of Stem Cell Sciences, Ankara – Turkey (Retired) • Chaim Hershko (Department of Medicine, Shaare Zedek Medical Center and Hebrew University Hadassah Medical School, Jerusalem, Israel) • Yeşim Aydınok (Ege University, İzmir, Turkey) • Şule Ünal (Hacettepe University, İhsan Doğramacı Child Hospital, Ankara, Turkey) • Amal El-Beshlawy (Cairo University, Egypt) • Miguel Abboud M.D. (Children’s Cancer Center of Lebanon, Beirut, Lebanon) • Elif Gülsüm Ümit (Edirne Sultan 1. Murat State Hospital, Edirne Turkey) • Kaan Kavaklı (Ege University Faculty of Medicine, İzmir, Turkey) • Ayşegül Ünüvar (Istanbul University Faculty of Medicine, İstanbul, Turkey) • Gül Nihal Özdemir (Istanbul Kanuni Sultan Süleyman Training & Research Hospital, Istanbul Turkey) • Muhlis Cem Ar (Istanbul University Faculty of Medicine, İstanbul, Turkey) • Reyhan Diz Küçükkaya (Retired, Istanbul, Turkey) • Yahya Büyükaşık (Hacettepe University Faculty of Medicine, Ankara, Turkey) • Elif Ünal İnce (AnkaraUniversity Faculty of Medicine, Ankara, Turkey) • Ayşegül Üner (Hacettepe University Faculty of Medicine, Ankara, Turkey) • Duygu Uçkan (Hacettepe University, İhsan Doğramacı Child Hospital, Ankara, Turkey) • Sema Anak (Istanbul University Faculty of Medicine, İstanbul, Turkey) 2 TABLE of CONTENTS Current Perspectives on Hematopoiesis and Hematopoietic Stem Cells………………………………………………7,8,9,10,11 Emin Kansu New insights on Iron Metabolism and Iron Deficiency Anemia…………………………………………………………...……12,13,14 Chaim Hershko Iron Overload in Thalassemias : Pathophysiology and Treatment ……………………………………………….…15,16,17,18,19 Yeşim Aydınok The screening programs and pre-natal diagnosis of Hemoglobinopathies: Where are we in the region?...20,21,22 Yeşim Aydınok Thalassemia traits difficult to diagnose and the significance in marital screenings…………………………………………..…23 Şule Ünal New therapeutic approaches in Thalassemias ………………………………………………………………………………………….……….24 Amal El-Beshlawy New science underlying potential treatment approaches for Sickle Cell Anemia………………………………………………..24 Miguel Abboud M.D Microangiopathic Hemolytic Anemias (MAHAs) Differential diagnosis and management…………………….….25,26,27 Elif Gülsüm Ümit Emerging therapeutic options and strategies in hemophilia: Novel factor concentrates……………….………….28,29,30 Kaan Kavaklı Risk factors and clinical management of inhibitor development in Hemophilia……………………..………………………30,31 Ayşegül Ünüvar Hematologic Manifestations and Complications of Gaucher Disease……………………………….……32,33,34,35,36,37,38 Gül Nihal Özdemir Disseminated Intravascular Coagulation (DIC) …. ……………………………………………………………………………….…………39,40 Muhlis Cem Ar When and whom to screen for Hereditary Thrombophilia? ……………………………………………………………..……………….41 Reyhan Diz Küçükkaya Diagnostic challenges in patients with undiagnosed bleeding problems…………………………………………………..42,43,44 Reyhan Diz Küçükkaya Acquired Aplastic Anemia…………………………………………………………………………………………….……………….…………………..45 Yahya Büyükaşık Congenital Dyserythropoietic Anemias (CDA): Diagnosis and Treatment……………………………………………………..46,47 Elif Ünal İnce Clinical and laboratory findings suggestive of hereditary bone marrow failures………….………………………………..48,49 Şule Ünal Stem Cell Transplantation in Fanconi’s Anemia …. ………………………………………………………………………………….49,50,51 Duygu Uçkan Long-term follow-up of pediatric stem cell transplant patients…………………………………………………………………………52 Sema Anak 3 Time 22 December 2017, Friday Opening Remarks Sabri Kemahlı (Secretary – General, ISH-EAD Coordinator, ISH-TSH School of Hematology) 08:30-08:45 Güner Hayri Özsan (Türk Hematoloji Derneği (President of Turkish Society of Hematology (TSH)) Session – I, Hemoglobinopathies Chair: Güner Hayri Özsan Current Perspectives on Hematopoiesis and Hematopoietic Stem Cells 08:45-09:10 Emin Kansu (Turkey) New insights on Iron Metabolism and Iron Deficiency Anemia 09:15-09:40 Chaim Hershko (Israel) Iron Overload in Thalassemias : Pathophysiology and Treatment 09:45-10:10 Yeşim Aydınok (Turkey) The screening programs and pre-natal diagnosis of Hemoglobinopathies: 10:15-10:40 Where are we in the region? Yeşim Aydınok (Turkey) 10:45-11:05 Coffee Break Chair: Ayşegül Ünüvar Thalassemia traits difficult to diagnose and the significance in marital screenings 11:05-11:30 Şule Ünal (Turkey) New therapeutic approaches in Thalassemias 11:35-12:00 Amal El-Beshlawy (Mısır) New science underlying potential treatment approaches for Sickle Cell Anemia 12:05-12:30 Miguel Abboud M.D. (Lebanon) 12:30 – 13:30 Lunch Session – II Hemostasis - Thrombosis and Storage Diseases Chair: Hemostasis - Şule Ünal Microangiopathic Hemolytic Anemias (MAHAs) Differential diagnosis and management 13:30 – 14:00 Elif Gülsüm Ümit (Turkey) Emerging therapeutic options and strategies in hemophilia: Novel factor concentrates 14:05 – 14:35 Kaan Kavaklı (Turkey) Risk factors and clinical management of inhibitor development in Hemophilia 14:40 – 15:10 Ayşegül Ünüvar (Turkey) Hematologic Manifestations and Complications of Gaucher Disease 15:15 – 15:45 Gül Nihal Özdemir (Turkey) 4 15:50 – 16:20 Coffee Break Disseminated Intravascular Coagulation (DIC) 16:20 – 16:50 Muhlis Cem Ar (Turkey) When and whom to screen for Hereditary Thrombophilia? 16:55 – 17:25 Reyhan Diz Küçükkaya (Turkey) Session-III Meet the Expert Session Diagnostic challenges in patients with undiagnosed bleeding problems 17:30 – 18:00 Reyhan Diz Küçükkaya (Turkey) 18:00 – 18:30 General Discussion Saat 23 December 2017, Saturday Session-VI Anemia and Bone Marrow Failure Chair: Sema Anak Acquired Aplastic Anemia 09:00 – 09:25 Yahya Büyükaşık (Turkey) Congenital Dyserythropoietic Anemias (CDA): Diagnosis and Treatment 09:30 – 09:55 Elif Ünal İnce (Turkey) Case Discussions: 10:00 – 10:45 Difficult Clinical Cases to be presented with Hematopathologic Discussions Ayşegül Üner (Turkey) 10: 45 – 1:05 Coffee Break Clinical and laboratory findings suggestive of hereditary bone marrow failures 11:05 – 11:30 Şule Ünal (Turkey) Stem Cell Transplantation in Fanconi’s Anemia 11:35 – 12:00 Duygu Uçkan (Turkey) 12:00-13:00 Lunch Session-V Meet the Expert Session Long-term follow-up of pediatric stem cell transplant patients 13:00-13:45 Sema Anak (Turkey) 13:45 – 14:00 General Discussion 14:00 – 14:15 Evaluation of the Scientific Program 14:15 – 14:30 Certificates to the Attendees Closing Remarks by 14:30 – 14:45 5 Güner Hayri Özsan (THD), Emin Kansu (ISH) Current Perspectives on Hematopoietic Stem Cell Dr. Emin Kansu (Turkey) Stem cell is defined as a primitive cell with a very high potential and infinite ability of self-renewal and differentiation into other cell types. Stem cells have unlimited potential for self-renewal to keep stem cell numbers and stem cell pool size constant life-long. These cells are clonal and have multilineage differentation features as well as engraftment potential to another host with complete reconstitution of hematopoiesis. Hematopoietic stem cells (HSC) have either symmetric or asymmetric divisions to keep their reserve constant and to differentiate to other cell types. HSCs can gotoapoptosiswhenneeded, enter into mitosis phase and also circulate in the peripheral blood at a constantrate.Themostimportant and useful property of stem cells is that of self-renewal. HSC is an adult stem cell derived from mesodermal stem cells (MSCs). MSCs as somatic stem cells also produce bone, muscle and cartilage stem cells. Adult HSCs have a long term self-renewal capacity and function as unipotent stem cells to produce erythroid, myeloid, lymphoid and megakaryocytic lineages. All these committed lineages are tightly regulated by hematopoietic growth factors, namely Erythropoietin (Epo), G-CSF /GM-CSF and Thrombopoietin (TPO) and IL-7. Current schema of hematopoiesis is shown in Figure – 1. Each committed HSC has a specific receptor on its surface for its respective ligand - hematopoietic growth factor (Figure-2). HSCs are composed of a combination of heterogenous cells with different phenotypic characteristics. Mostly HSCs have a CD34 (+) and CD38(-) phenotype (Figure – 1). The stem cells or primitive progenitors from various tissues in adults share several phenotypic characteristics. 1. SELF - RENEWAL 3. MULTIPOTENTIALITY RBCs CMP Plts PMN SELF-RENEWAL CAPACITY GIMP MEG HSC D Cell LT-HSC ST-HSC MPP CD 34 + CD 34 + CD 34 + CD 38- CD 38- CD 38+ T - Cells CD 90+ CD 90- CD 90- B - Cells Go : 70 % 35 % 5 % 2. ENGRAFMENT CLP Common Lymphoid NK - Cells & progenitor RECONSTITUTION CLP Figure – 1 . Current schema of hematopoiesis with self-renewal capacity, multipotentiality and engraftment / reconstitution features 6 During embryonic stages and fetal life, human HSCs start to appear in aorta- gonad-mesonephros (AGM), then switch to yolk sac stage for a very brief period followed by placental period and finally into the fetal bone marrow. During embryonic development, blood forming stem cells (HSCs) go from the yolk sac region to AGM. As HSCs divide some of the daughter cells remain as stem cells and continue dividing while others become committed to specific lineages. HSCs go into different stages of development in mouse and in human (Figures-2 , -3, -4 and -5). HSCs can be found in peripheral blood, bone marrow and cord blood. CYTOKINE ACTION ERYTHTROPOIETIN HEMATOPOIETIC G-CSF / GM-CSF GROWTH FACTOR RECEPTOR THROMBOPOIETIN HSC COMMITTED PROGENITORS Figure – 2.