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Book Details
Abstract
This issue of Hematology/Oncology Clinics, edited by Dr. Ali Taher, focuses on Thalassemia. Topics include, but are not limited to, Molecular basis and genetic modifiers; Evolving spectrum of epidemiology; Clinical classification; Ineffective erythropoiesis, anemia and iron overload; Hypercoagulability and vascular disease; Clinical complications and their management; Transfusion and iron chelation therapy; Hematopoietic Stem Cell Transplantation in Thalassemia; Gene therapy and genome editing; Emerging therapies; Quality of life; Advances in understanding pathophysiology and treatment of fertility, pregnancy, and prenatal diagnosis in Thalassemia; and MRI for iron overload.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Thalassemia | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| CONSULTING EDITORS | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Preface: Thalassemia | vii | ||
| The Evolving Spectrum of the Epidemiology of Thalassemia | vii | ||
| Molecular Basis and Genetic Modifiers of Thalassemia | vii | ||
| Clinical Classification, Screening, and Diagnosis for Thalassemia | vii | ||
| Ineffective Erythropoiesis: Anemia and Iron Overload | viii | ||
| Clinical Complications and Their Management | viii | ||
| Hypercoagulability and Vascular Disease | viii | ||
| Interaction of Transfusion and Iron Chelation in Thalassemias | viii | ||
| Iron Chelation Therapy as a Modality of Management | ix | ||
| MRI for Iron Overload in Thalassemia | ix | ||
| Fertility and Pregnancy in Women with Transfusion-Dependent Thalassemia | ix | ||
| Hematopoietic Stem Cell Transplantation in Thalassemia | ix | ||
| Gene Therapy and Genome Editing | x | ||
| Emerging Therapies | x | ||
| HEMATOLOGY/ONCOLOGY\rCLINICS OF NORTH AMERICA\r | xi | ||
| FORTHCOMING ISSUES | xi | ||
| June 2018 | xi | ||
| August 2018 | xi | ||
| October 2018 | xi | ||
| RECENT ISSUES | xi | ||
| February 2018 | xi | ||
| December 2017 | xi | ||
| October 2017 | xi | ||
| Erratum | xiii | ||
| Preface: Thalassemia\r | xv | ||
| The Evolving Spectrum of the Epidemiology of Thalassemia | 165 | ||
| Key points | 165 | ||
| INTRODUCTION | 165 | ||
| WORLD DISTRIBUTION | 166 | ||
| DETERMINING THE ACCURATE FREQUENCY OF THE THALASSEMIAS IN DIFFERENT POPULATIONS | 167 | ||
| Standard Methods of Assessment | 167 | ||
| The Clinical Value of Micromapping | 168 | ||
| REASONS FOR THE HIGH FREQUENCY OF THE DIFFERENT FORMS OF THALASSEMIA | 168 | ||
| Malaria Resistance | 168 | ||
| The Mechanisms of Malaria Resistance | 168 | ||
| Epistatic Interactions of Thalassemia and Hemoglobin Variants | 169 | ||
| Malaria and the Different Frequencies of the Thalassemias Over Short Geographic Distances | 169 | ||
| Other Factors Involved in the Frequency of the Thalassemias | 171 | ||
| Clinical Implications of the Studies of the Relative Distribution of the Thalassemias | 171 | ||
| THALASSEMIA FOR THE FORESEEABLE FUTURE | 171 | ||
| The Frequency of Thalassemia in the Foreseeable Future | 171 | ||
| The Effects of Emigration | 172 | ||
| Risks of Different Forms of Malaria for Some Types of Thalassemia | 172 | ||
| REQUIREMENTS FOR THE FUTURE | 172 | ||
| SUMMARY | 173 | ||
| ACKNOWLEDGMENTS | 174 | ||
| REFERENCES | 174 | ||
| Molecular Basis and Genetic Modifiers of Thalassemia | 177 | ||
| Key points | 177 | ||
| INTRODUCTION | 177 | ||
| HUMAN α- AND β-GLOBIN GENE LOCI | 178 | ||
| GLOBIN GENE EXPRESSION AND HEMOGLOBIN PRODUCTION DURING DEVELOPMENT | 179 | ||
| SYNTHESIS OF HEMOGLOBIN DURING ERYTHROPOIESIS | 179 | ||
| REGULATION OF GLOBIN GENE EXPRESSION AND SWITCHING | 180 | ||
| MOLECULAR DEFECTS DOWN-REGULATING α-GLOBIN EXPRESSION CAUSING α-THALASSEMIA | 181 | ||
| GENOTYPE-PHENOTYPE CORRELATION OF α-THALASSEMIA | 182 | ||
| MOLECULAR DEFECTS CAUSING β-THALASSEMIA | 183 | ||
| MOLECULAR AND CELLULAR PATHOLOGY OF β-THALASSEMIA | 184 | ||
| GENOTYPE-PHENOTYPE CORRELATION AND GENETIC MODIFIERS OF β-THALASSEMIA | 186 | ||
| GENETIC MODIFIERS THAT WORSEN THE SEVERITY OF β-THALASSEMIA | 187 | ||
| GENETIC MODIFIERS THAT AMELIORATE SEVERITY OF β-THALASSEMIA | 187 | ||
| SUMMARY | 188 | ||
| ACKNOWLEDGMENTS | 188 | ||
| REFERENCES | 188 | ||
| Clinical Classification, Screening and Diagnosis for Thalassemia | 193 | ||
| Key points | 193 | ||
| INTRODUCTION | 193 | ||
| CLINICAL CLASSIFICATION OF THALASSEMIA | 194 | ||
| Transfusion-Dependent Thalassemia | 195 | ||
| Clinical presentation, history, and physical examination | 195 | ||
| Non–Transfusion-Dependent Thalassemia | 196 | ||
| Clinical presentation, history, and physical examination | 198 | ||
| SCREENING AND DIAGNOSIS OF THALASSEMIA | 198 | ||
| Screening Tests for Thalassemia Carriers in a Population Approach | 198 | ||
| One-tube osmotic fragility test | 200 | ||
| Advantages | 200 | ||
| Disadvantages | 200 | ||
| Red blood cell indices: Mean corpuscular volume and mean corpuscular hemoglobin | 201 | ||
| Advantages | 201 | ||
| Disadvantages | 201 | ||
| Dichlorophenol indophenol precipitation test | 201 | ||
| Advantages | 202 | ||
| Disadvantages | 202 | ||
| A combination of thalassemia screening techniques | 202 | ||
| A combination of one-tube osmotic fragility test and dichlorophenol indophenol tests | 202 | ||
| A combination of mean corpuscular volume and dichlorophenol indophenol testing | 202 | ||
| Diagnostic Tests for Thalassemia | 202 | ||
| Interpretation of the peripheral blood smear | 202 | ||
| Hemoglobin analysis | 204 | ||
| DNA or molecular analysis | 205 | ||
| SUMMARY | 207 | ||
| REFERENCES | 207 | ||
| Ineffective Erythropoiesis: Anemia and Iron Overload | 213 | ||
| Key points | 213 | ||
| ERYTHROPOIESIS AND THE ERYTHROBLASTIC ISLAND | 214 | ||
| Hepcidin and Iron Homeostasis | 214 | ||
| Stress and Ineffective Erythropoiesis | 215 | ||
| Iron Overload and Its Therapeutic Targeting | 217 | ||
| CONCLUDING REMARKS | 218 | ||
| ACKNOWLEDGMENTS | 218 | ||
| REFERENCES | 218 | ||
| Clinical Complications and Their Management | 223 | ||
| Key points | 223 | ||
| INTRODUCTION | 223 | ||
| CARDIAC COMPLICATIONS | 224 | ||
| Cardiac Dysfunction | 224 | ||
| Arrhythmia | 225 | ||
| LIVER DISEASE | 226 | ||
| Iron Overload | 226 | ||
| Viral Hepatitis | 227 | ||
| Hepatocellular Carcinoma | 227 | ||
| ENDOCRINE COMPLICATIONS | 228 | ||
| Hypogonadotropic Hypogonadism | 228 | ||
| Growth Hormone Deficiency | 228 | ||
| Hypothyroidism | 229 | ||
| Diabetes | 229 | ||
| Hypoparathyroidism | 229 | ||
| Adrenal Insufficiency | 229 | ||
| BONE DISEASE | 230 | ||
| HYPERCOAGULABILITY AND VASCULAR DISEASE | 230 | ||
| Pulmonary Hypertension | 231 | ||
| OTHER COMPLICATIONS | 231 | ||
| REFERENCES | 232 | ||
| Hypercoagulability and Vascular Disease | 237 | ||
| Key points | 237 | ||
| INTRODUCTION | 237 | ||
| PATHOPHYSIOLOGY | 238 | ||
| CLINICAL THROMBOSIS AND VASCULAR DISEASE | 239 | ||
| PREVENTION AND MANAGEMENT | 241 | ||
| REFERENCES | 242 | ||
| Interaction of Transfusion and Iron Chelation in Thalassemias | 247 | ||
| Key points | 247 | ||
| INTRODUCTION | 247 | ||
| OBJECTIVES OF TRANSFUSION IN THALASSEMIAS | 248 | ||
| BODY IRON CONTENT AND IMPACT OF TRANSFUSION | 249 | ||
| MECHANISMS OF BODY IRON DISTRIBUTION IN THALASSEMIAS | 249 | ||
| EFFECT OF BLOOD TRANSFUSION REGIMEN ON IRON DISTRIBUTION | 251 | ||
| Effect of Cumulative Blood Transfusion on Iron Distribution | 251 | ||
| Effect of Intensity of Transfusion Regimen on Iron Accumulation and Iron Distribution | 251 | ||
| Differences in the Activity of Erythron with Transfusion as Marked by Soluble Transferrin Receptors | 252 | ||
| Control of Iron Retention in Tissues Through Ferroportin-Hepcidin Interactions | 253 | ||
| INTERACTION OF BLOOD TRANSFUSION AND CHELATABLE IRON POOLS | 253 | ||
| Interaction of Transfusion with Chelatable Iron Pools | 253 | ||
| Interaction of Blood Transfusion with Chelator Dose Needed for Iron Balance | 254 | ||
| Other Factors Affecting Extrahepatic Iron Removal with Chelation Therapy | 255 | ||
| REFERENCES | 255 | ||
| Iron Chelation Therapy as a Modality of Management | 261 | ||
| Key points | 261 | ||
| INTRODUCTION | 261 | ||
| Quantifying Iron Overload | 262 | ||
| Properties of Iron Chelators in Clinical Use | 264 | ||
| Objectives of Iron Chelation Therapy in Thalassemia | 264 | ||
| The Impact of Transfusional Iron Intake on Chelation Efficacy | 264 | ||
| The Importance of Existing Total Body Iron Burden on Choice of Chelator Dosing and Regimen | 264 | ||
| Cardiac Iron Clearance | 266 | ||
| Is There Any Impact of Hepatic Iron on Cardiac Iron Clearance? | 267 | ||
| Iron Chelation Therapy for Prevention and Reversal of Endocrine Complications in Thalassemia | 267 | ||
| Importance of Adherence | 269 | ||
| Chelation Therapy in Non-Transfusion-Dependent Thalassemia | 269 | ||
| REFERENCES | 270 | ||
| MRI for Iron Overload in Thalassemia | 277 | ||
| Key points | 277 | ||
| INTRODUCTION | 277 | ||
| WHY MRI IS A CENTRAL PART OF IRON OVERLOAD DIAGNOSIS: LIMITATIONS OF ALTERNATIVE TOOLS | 277 | ||
| PRINCIPLES OF MRI | 280 | ||
| General Principles | 280 | ||
| How Does MRI Measure Iron? | 281 | ||
| ASSESSMENT OF IRON OVERLOAD IN THE LIVER | 282 | ||
| The Signal Intensity Ratio Technique | 282 | ||
| Relaxometry Methods: T2 and T2* | 282 | ||
| ASSESSMENT OF IRON OVERLOAD IN THE HEART | 285 | ||
| ASSESSMENT OF IRON OVERLOAD IN OTHER ORGANS | 288 | ||
| INTERPRETING MRI RESULTS: A PRACTICAL APPROACH TO FIRST USE OF MRI AND FOLLOWING PATIENTS | 288 | ||
| SUMMARY | 290 | ||
| REFERENCES | 290 | ||
| Fertility and Pregnancy in Women with Transfusion-Dependent Thalassemia | 297 | ||
| Key points | 297 | ||
| IRON TOXICITY AND THE FEMALE REPRODUCTIVE SYSTEM | 298 | ||
| Mechanisms | 298 | ||
| Evaluation | 298 | ||
| PREGNANCIES IN WOMEN WITH TRANSFUSION-DEPENDENT THALASSEMIA | 299 | ||
| Planning for Pregnancy: Considerations Prior to and During Pregnancy | 304 | ||
| Cardiac | 304 | ||
| Thrombotic risk | 305 | ||
| Infection | 305 | ||
| Liver disease | 305 | ||
| Endocrine | 305 | ||
| Other considerations | 305 | ||
| Attaining Pregnancy | 307 | ||
| MANAGEMENT DURING PREGNANCY AND PERINATAL PERIOD | 307 | ||
| Transfusions | 307 | ||
| Iron Chelation | 307 | ||
| Cardiac, Endocrine, and Gastroenterology Evaluation | 308 | ||
| Perinatal | 308 | ||
| Postnatal Considerations | 308 | ||
| Social/Psychological/Ethical Considerations | 309 | ||
| ATTAINING A FAMILY: OTHER OPTIONS | 309 | ||
| PRENATAL SCREENING FOR THALASSEMIA: AN UPDATE | 309 | ||
| FUTURE METHODS OF PRENATAL DIAGNOSIS | 310 | ||
| REFERENCES | 310 | ||
| Hematopoietic Stem Cell Transplantation in Thalassemia | 317 | ||
| Key points | 317 | ||
| INTRODUCTION | 317 | ||
| PRETRANSPLANTATION RISK STRATIFICATION | 318 | ||
| CONDITIONING REGIMEN | 319 | ||
| DONOR-RECIPIENT CHIMERISM | 319 | ||
| IN THALASSEMIA MAJOR | 320 | ||
| TRANSPLANTATION | 320 | ||
| UNRELATED UMBILICAL CORD BLOOD TRANSPLANTATION IN THALASSEMIA MAJOR | 322 | ||
| (HAPLO- HSCT) IN THALASSEMIA MAJOR | 323 | ||
| SUMMARY/DISCUSSION | 324 | ||
| REFERENCES | 325 | ||
| Gene Therapy and Genome Editing | 329 | ||
| Key points | 329 | ||
| INTRODUCTION | 329 | ||
| RATIONALE FOR GLOBIN GENE TRANSFER TO CURE β-THALASSEMIA | 330 | ||
| GLOBIN GENE TRANSFER | 330 | ||
| How It All Started: The First 10 Years (–2000): Preclinical Proof-of-Principle and Safety Studies | 330 | ||
| The Following 10 Years | 332 | ||
| The present state of affairs: Gene therapy trials | 333 | ||
| Essential features of globin gene therapy trials | 336 | ||
| The host | 336 | ||
| The hematopoietic progenitor cells | 337 | ||
| The cytoreduction | 337 | ||
| The transduction efficiency | 337 | ||
| The risks of globin gene therapy | 337 | ||
| GENE EDITING | 338 | ||
| SUMMARY AND PERSPECTIVES | 339 | ||
| REFERENCES | 339 | ||
| Emerging Therapies | 343 | ||
| Key points | 343 | ||
| INTRODUCTION | 343 | ||
| EMERGING THERAPIES IN CLINICAL TRIALS | 344 | ||
| INNOVATIVE THERAPIES IN PRECLINICAL STAGES | 345 | ||
| NOVEL TOOLS FOR DRUG DEVELOPMENT AND THERAPY DISCOVER | 348 | ||
| DISCUSSION | 348 | ||
| ACKNOWLEDGMENTS | 349 | ||
| REFERENCES | 349 |