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Chronic Myelomonocytic Leukemia

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Chronic Myelomonocytic Leukemia BASIC PHYSIOPATHOLOGY OF GENERAL HEMATOLOGY A SYNOPSIS OF HEMATOLOGY Pierre-Michel Schmidt Pierre Cornu Anne Angelillo-Scherrer with the contribution of : Claire Abbal Anne Cairoli Martine Jotterand Stéphane Quarroz Pieter Canham van Dijken Service d'Hématologie, CHUV - Lausanne Version 16.0, 2014 Universitätklinik für Hämatologie, Inselspital - Bern CONTENTS Part 1 : Red Blood Cell (RBC) pathology PAGES Differentiation of blood cells 10 Normal ranges in hematology 11 Erythropoiesis 12 Evaluation of anemia 13 - 14 Reticulocytes 14 Mechanisms of anemia 15 - 17 Pathophysiological classification of anemias 18 Hyporegenerative normocytic normochromic anemia 19 Anemia of renal failure 20 Pure red cell aplasia / Erythroblastopenia 21 Bone marrow aplasia 22 Aplastic anemia 23 - 25 Microcytic hypochromic anemia 26 - 41 Iron metabolism 27 Hepcidin regulation 28 Iron cycle 29 Transferrin cycle / Ferritin, transferrin receptor and DMT 1 regulation 30 Iron deficiency anemia 31 - 34 Physiological iron losses and iron bioavailability 31 Stages of iron deficiency development / Serum iron, transferin and ferritin 32 Etiology of iron deficiency anemia 33 Treatment of iron deficiency 34 Anemia of chronic disorders / Inflammatory anemia 35 Anemia with iron utilization disorder / Sideroblastic anemia 36 Structure of hemoglobin / Interaction O2 and 2,3-DPG 37 Heme synthesis / Porphyrias 38 Globin synthesis 39 Hemoglobin affinity for oxygen 40 Hemoglobin degradation 41 Macrocytic normochromic hyporegenerative anemia 42 - 55 Pathophysiology of macrocytic megaloblastic anemia 43 Chemical structure of vitamin B12 and folates 44 Vitamin B12 and folates / General data 45 Absorption of vitamin B12 46 LDH and anemia 47 2 CONTENTS (2) PAGES DNA synthesis anomaly and consequences / Schilling test 48 Normal and megaloblastic erythropoiesis 49 Causes of vitamin B12 deficiency 50 Pernicious anemia 51 - 53 Causes of folate deficiency 54 Workup of macrocytic anemia 55 Normocytic normochromic regenerative anemia 56 - 72 Acute blood loss 56 - 57 Hemolytic anemia / Basic data 58 - 59 Hemolytic anemia due to corpuscular defect 60 - 81 RBC glycolysis 61 - 62 RBC enzymopathy 63 - 65 Glucose-6-phosphate dehydrogenase deficiency 64 - 65 Structure of RBC membrane 66 Anomaly of RBC membrane 67 - 72 Hereditary spherocytosis (autosomal dominant) 68 - 69 Paroxysmal Nocturnal Hemoglobinuria 70 - 72 Genetic anomalies of hemoglobin (Hemoglobinopathies) 73 - 81 Classification 73 - 74 Thalassemic syndromes 75 - 78 Physiopathology 75 α-thalassemia 76 β-thalassemia 77 Clinical consequences of thalassemia major / intermedia 78 Sickle cell disease 79 - 80 Combined genetic anomalies of hemoglobin 81 Hemolytic anemia due to extracorpuscular defect 82 - 87 Immune hemolytic anemia 82 Toxic hemolytic anemia 83 - 84 Hemolytic anemia of infectious origin 85 Hemolytic anemia due to mechanic RBC fragmentation 86 - 87 Thrombotic thrombocytopenic purpura (TTP) / Hemolytic uremic syndrome (HUS) 86 Thrombotic microangiopathy / Diagnostic algorithm 87 Part 2 : White Blood Cell (WBC) pathology Differential leukocyte count 89 Neutrophil granulocytes kinetics 90 3 CONTENTS (3) PAGES Etiology of neutrophilic leukocytosis 91 Toxic changes of neutrophils 92 Myelocytosis and erythroblastosis 93 Neutropenia 94 - 96 Hereditary morphological neutrophil anomalies 97 Eosinophils 98 Basophils / Mastocytes 99 Monocytes / Macrophages 100 - 101 Lymphocytes 102 - 113 Lymphoid organs / B and T lymphocytes in bone marrow and peripheral blood 102 B-lymphocytes 103 Steps of B-lymphocyte maturation in secondary lymphoid organs 104 T-lymphocytes / Thymic selection 105 B- and T-lymphocyte differentiation markers 106 NK-lymphocytes (Natural Killer lymphocytes) 107 Lymphocytes / Immune response 108 - 111 Lymphocytosis / Lymphopenia / Plasmacytosis / Mononucleosis syndrome 112 - 113 Tumors of hematopoietic and lymphoid tissues 114 - 202 WHO classification 2008 114 - 116 Myeloid neoplasms 117 - 159 Myeloproliferative neoplasms 118 - 134 Polycythemia Vera 119 - 120 Differential diagnosis of erythrocytosis 121 - 123 Chronic myelogenous leukemia 124 - 126 Essential thrombocythemia 127 - 129 Differential diagnosis of thrombocytosis 130 Primary myelofibrosis 131 - 132 Chronic neutrophilic leukemia / Chronic eosinophilic leukemia, NOS 133 Mastocytosis 134 Myeloid and lymphoid neoplasms with eosinophilia and anomalies of PDGFRA, PDGFRB or FGFR1 135 Myelodysplastic syndromes (MDS) 136 - 145 General features / Myelodysplasia 136 - 137 Morphological signs of myelodysplasia 138 Classification of MDS / Peripheral blood and bone marrow features 139 Differential diagnosis of MDS and acute myeloid leukemia (AML) / Other anomalies in MDS 140 4 CONTENTS (4) PAGES Prognostic scores of MDS / IPSS and WPSS / revised IPSS (IPSS-R) 141 - 142 Other adverse prognostic factors in MDS 143 Complications / Course / Survival 144 Treatment of MDS 145 Myelodysplastic / myeloproliferative neoplasms : Chronic myelomonocytic leukemia 146 Acute myeloid leukemia (AML) 147 - 159 Epidemiology 147 Clinical features of AML 148 Bone marrow and peripheral blood features 149 WHO classification 2008 150 - 153 Prognostic factors 154 Karnofsky performance status 155 Therapeutical principles 156 Chemotherapy of AML 157 Kinetics of leukemic cells in relation with treatment 158 Hematopoietic stem cell transplantation 159 Lymphoid neoplasms 160 - 202 General data 160 - 165 Simplified classification (WHO 2008) 160 Proof of monoclonality 161 Clinical stage / ECOG clinical performance status / Prognostic factors / Clinical behaviour 161 Staging (Ann Arbor) 162 Initial assessment / IPI and aaIPI scores 163 Treatment of lymphoid neoplasms 164 B-cell differentiation / Relationship to major B-cell neoplasms 165 Precursor B or T-cell lymphoid neoplasms 166 - 171 Lymphoblastic leukemia / lymphoma 166 B-cell lymphoblastic leukemia / lymphoma, NOS 167 B-cell lymphoblastic leukemia / lymphoma with recurrent genetic anomalies 168 T-cell lymphoblastic leukemia / lymphoma 169 Immunological markers of ALL- B and ALL-T 170 Treatment of lymphoblastic leukemia / lymphoma 171 Mature B-cell lymphoid neoplasms 172 - 193 Relative frequency of mature B-cell lymphoid neoplasms 172 Diffuse large B-cell lymphoma (DLBCL) 173 Chronic lymphocytic leukemia (CLL) 174 - 178 Definition / Symptoms and clinical features / Peripheral blood count 174 Rai and Binet stages 175 5 CONTENTS (5) PAGES Course / Complications / Differential diagnosis 176 Prognostic factors 177 Treatment of CLL 178 Follicular lymphoma (FL) 179 Lymphoplasmacytic lymphoma / Waldenström macroglobulinemia 180 Splenic B-cell marginal zone lymphoma (SMZL) 181 Splenic B-cell leukemia / lymphoma, unclassifiable 181 Splenic diffuse red pulp small B-cell lymphoma (SMZL-diffuse variant) 181 Hairy cell leukemia-variant ("prolymphocytic variant") 181 Mantle cell lymphoma (MCL) 182 Hairy Cell Leukemia 183 Prolymphocytic B-cell leukemia 183 Burkitt lymphoma 184 Burkitt type acute lymphoblastic leukemia 184 Plasma cell neoplasms 185 - 192 Definition / WHO classification 2008 / Heavy chain diseases 185 Diagnostic work-up / Frequence of the different paraproteinemias 186 Free light chains (FLC) measurement in serum / κ /λ ratio 187 Differential diagnosis of MGUS, smoldering myeloma and plasma cell myeloma / Clinical course 188 Prognostic factors / Durie and Salmon staging 189 Prognostic factors / Impact of ISS and combination ISS with κ /λ ratio on survival 190 Complications of plasma cell myeloma 190 Treatment 191 Risk related treatment algorithms 192 Immunological markers, cytogenetics and molecular biology in B-cell lymphoid leukemias 193 Mature T- and NK-cell lymphoid neoplasms 194 - 198 Relative frequency of mature T / NK cell leukemia / lymphoma 194 Peripheral T-cell lymphoma NOS 195 Angioimmunoblastic T cell lymphoma 195 Adult T-cell leukemia / lymphoma 196 Anaplastic large cell lymphoma 196 T-cell prolymphocytic leukemia 197 T-cell large granular lymphocytic leukemia 197 Mycosis fungoides / Sézary syndrome 198 Other mature T- / NK-cell lymphomas 198 6 CONTENTS (6) PAGES Hodgkin lymphoma 199 - 202 Symptoms / Clinical features / Histology 199 Staging / Cotswolds revision of Ann Arbor classification 200 Diagnosis and prognostic staging 201 Treatment / Prognosis and response predictive factors 202 Part 3 : Hemostasis Exploration methods 205 Thrombus and embolus 205 Main actors of hemostasis 206 Role of the liver in hemostasis 207 Steps of hemostasis / Primary hemostasis 208 - 209 Von Willebrand factor 210 Production of platelet from the megakaryocyte 211 Secondary hemostasis / Coagulation 212 Tissue factor : major initiator of coagulation 213 Coagulation factors 214 - 215 Vitamin K dependent coagulation factors 215 Coagulation cascade 216 - 218 Classical scheme 216 Conceptual changes 217 - 218 Factor XIII and fibrin stabilization 219 Natural anticoagulants 220 Tertiary hemostasis / Fibrinolysis 221 Hemorrhagic syndrome / Primary hemostasis 222 - 231 Vascular purpura 222 Prolongation of occlusion time (PFA-100TM / PFA-200TM) 223 Acquired thrombopathy 224 Hereditary thrombopathy 225 Thrombocytopenia 226 - 231 Definition / Hemorrhagic risk / Recommendations 226 Thrombocytopenia in the setting of bi- or pancytopenia 227 Solitary central thrombocytopenia 227 Solitary peripheral thrombocytopenia 228 - 230 7 CONTENTS (7) PAGES Non immunological thrombocytopenia 228 Immunological thrombocytopenia 229 Heparin induced thrombocytopenia (HIT) 229 Primary immune thrombocytopenia (PIT) 230 Investigation of thrombocytopenia 231 Hemorrhagic syndrome / Coagulation
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