Details

The Peripheral T-Cell Lymphomas

1. Aufl.

von: Owen A. O'Connor, Won Seog Kim, Pier L. Zinzani
167,99 €
Verlag:	Wiley-Blackwell
Format:	PDF
Veröffentl.:	19.02.2021
ISBN/EAN:	9781119671329
Sprache:	englisch
Anzahl Seiten:	416

In den Warenkorb

Als Gutschein

DRM-geschütztes eBook, Sie benötigen z.B. Adobe Digital Editions und eine Adobe ID zum Lesen.

Beschreibungen

Titelbeschreibung

THE PERIPHERAL T-CELL LYMPHOMAS Provides a comprehensive look at Peripheral T-Cell lymphomas, including the group’s unique geographic distribution, underlying genetics, and novel treatments Peripheral T-Cell lymphomas (PTCL) are a diverse group of lymphoid malignancies that develop from mature T cells and natural killer (NK) cells. PTCL represent 10-15% of all cases of non-Hodgkin lymphoma in the US, and up to 20-25% of cases in South America, Asia, and other regions around the world. The role of different etiologic factors and the variation of geographic distribution makes PTCL one of the most difficult types of cancer to understand and treat. For the first time in a single volume, The Peripheral T-Cell Lymphomas presents a comprehensive survey of this complex and rare group of blood cancers. Featuring contributions from an international team of leading authorities in the various aspects of PTCL, this authoritative text covers biology, epidemiology, classification, approved and emerging drugs, molecular genetics, and more. Detailed clinical chapters address diagnosis, prognosis, and treatment of each of the major PTCL subtypes identified in the 2018 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. This much-needed resource: <ul><li>Covers the biological basis, epidemiology, classification, and treatment of PTCL</li><li>Discusses the future of the field, including global collaboration efforts and novel approaches to PCTL</li><li>Explores the role of biologics in PTCL and autologous and allogeneic stem-cell transplantation</li><li>Offers new insights on molecular pathogenesis, innovative therapeutics, and novel drug combinations</li><li>Features contributions from the Chairs The T-Cell Lymphoma Forum: the world’s largest meeting focused on PTCL</li></ul> Reflecting the unique epidemiology and genetic diversity of the PTCL, The Peripheral T-Cell Lymphomas is an indispensable source of data, insight, and references for the medical community, particularly oncologists and hematologists in both training and practice.

Inhaltsverzeichnis

Contributors xix About the Companion Website xxiii Part I Biological Basis of the Peripheral T-cell Lymphomas 1 1 The Fundamentals of T-cell Lymphocyte Biology 3 Claudio Tripodo and Stefano A. Pileri Introduction 3 General View of the Differentiation and Function of T Lymphocytes 3 The T-cell System as a Frame for Peripheral T-cell Lymphoma: Taking Plasticity into Account 5 Must Reads 7 References 7 2 Mechanisms of T-cell Lymphomagenesis 9 François Lemonnier, Philippe Gaulard and Laurence de Leval Introduction 9 Oncogenic Events in the Transformation of T or Natural Killer Cells 9 Genetic Lesions 9 Deregulated Pathways in Peripheral T-cell Lymphoma Oncogenesis (Figure 2.1, Table 2.1) 10 Signaling Pathways 13 Cell-cycle Control 14 Immune Surveillance 14 Role of the Microenvironment in Peripheral T-cell Lymphoma 15 The Model of Angio-immunoblastic T-cell Lymphoma and T Follicular Helper-derived Peripheral T-cell Lymphoma 15 Specific Microenvironment Components Present in Other Primary Cutaneous T-cell Lymphoma Entities 16 Underlying Factors Favoring the Tumor Transformation 18 Viruses 18 Chronic Antigenic Stimulation 19 Other Factors 19 Cell of Origin (Table 2.1) 20 Conclusion 22 Must Reads 22 References 22 3 Epigenetics of T-cell Lymphoma 27 H. Miles Prince, Jasmine Zain, Anas Younes, Sean Whittaker, Owen A. O’Connor and Sean Harrop Introduction 27 Epigenetic Pathways Altered in T-cell Lymphoma 27 Epigenetic Changes Within Specific T-cell Lymphoma Subtypes 31 Peripheral T-cell Lymphoma Not Otherwise Specified 32 Angioimmunoblastic T-cell Lymphoma and Peripheral T-cell Lymphoma with T Follicular Helper Phenotype 32 Anaplastic Large-cell Lymphoma 33 Adult T-cell Leukemia/Lymphoma 33 Intestinal T-cell Lymphoma 34 Hepatosplenic T-cell Lymphomas 34 Extranodal Natural Killer/T-cell Lymphoma 34 Mycosis Fungoides and Sézary Syndrome 35 Established and Emerging Drugs Targeting the T-cell Lymphoma Epigenome 35 DNA Methyltransferase Inhibitors 35 Isocitrate Dehydrogenase Inhibitors 36 EZH2 Inhibitors 37 BET Inhibitors 38 Protein Arginine Methyltransferases Inhibitors 38 Combination Therapies Involving Epigenetic Targeting Agents 38 Future Directions 38 Must Reads 39 References 39 4 Animal Models of T-cell Lymphoma 47 Keiichiro Hattori, Raksha Shrestha, Tatsuhiro Sakamoto, Manabu Kusakabe and Mamiko Sakata-Yanagimoto Introduction 47 Angioimmunoblastic T-cell Lymphoma 50 The ROQUIN Mouse Model 50 The Mouse Models Recapitulating Human Angioimmunoblastic T-cell Lymphoma Genomic Features 50 Tet2 Gene Trap Mice 50 G17V RHOA Mouse Model 50 PDX Models of Angioimmunoblastic T-cell Lymphoma 51 Anaplastic Large T-cell Lymphoma 51 Viral and Chimeric Models 51 Transgenic Models 51 CRISPR-Based Models 52 PDX Models of Anaplastic Large-Cell Lymphomas 52 Human T-cell Lymphotropic Virus Type 1 Adult T-cell Leukemia/Lymphoma 52 Mice Expressing HTLV-1 Viral Proteins 52 PDX Models of Adult T-cell Leukemia/Lymphoma 52 Cutaneous T-cell Lymphoma 53 Enteropathy-associated T-cell Lymphoma 53 Conclusion 53 Must Reads 53 References 54 Part II Epidemiology and Classification of the PTCL 57 5 Geographic Distribution of the Peripheral T-cell Lymphomas 59 Global Epidemiology Amulya Yellala, Avyakta Kallam and James O. Armitage Historical Perspective 59 Epidemiology 60 Peripheral T-cell Lymphoma, Not Otherwise Specified 60 Angioimmunoblastic T-cell Lymphoma 61 Anaplastic Large-cell Lymphoma 61 Adult T-cell Lymphoma/Leukemia (HTLV Associated) 62 Extranodal NK/T-cell Lymphomas 62 T-cell Prolymphocytic Leukemia 62 Large Granular Lymphocytic Leukemia 62 Primary Cutaneous Gamma/Delta PTCL 63 Enteropathy Associated T-cell Lymphomas and Monomorphic Epitheliotropic Intestinal T-cell lymphoma 63 Hepatosplenic T-cell Lymphoma 63 The Cutaneous T-cell Lymphomas 63 Conclusion 63 Must Reads 64 References 64 6 Classification of the Peripheral T-cell Lymphomas 69 Neval Ozkaya and Elaine S. Jaffe Introduction 69 Angioimmunoblastic T-cell Lymphoma and Other Nodal Lymphomas of T follicular Helper Cell Origin 69 Angioimmunoblastic T-cell Lymphoma 70 Follicular T-cell Lymphoma 71 Nodal Peripheral T-cell Lymphoma with T-follicular Helper Phenotype 71 Peripheral T-cell Lymphoma Not Otherwise Specified 71 Anaplastic Large-cell Lymphomas 72 Anaplastic Large-cell Lymphoma, ALK-Positive 72 Anaplastic Large-cell Lymphoma, ALK-Negative 72 Breast Implant-associated Anaplastic Large-cell Lymphoma (Provisional) 73 Adult T-cell Leukemia/Lymphoma 74 Intestinal T-cell Lymphomas 74 Enteropathy-associated T-Cell Lymphoma 75 Monomorphic Epitheliotropic Intestinal T-cell Lymphoma 76 Intestinal T-cell ymphoma, Not Otherwise Specified 76 Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract (Provisional) 77 NK-Cell Enteropathy 78 Hepatosplenic T-cell Lymphoma 78 Mycosis Fungoides 78 Sézary Syndrome 79 Primary Cutaneous CD30-positive T-cell Lymphoproliferative Disorders 79 Lymphomatoid Papulosis 79 Primary Cutaneous Anaplastic Large-cell Lymphoma 80 Subcutaneous Panniculitis-like T-cell Lymphoma 80 Primary Cutaneous Gamma–Delta T-cell Lymphoma 80 Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-cell Lymphoma (Provisional) 81 Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder (Provisional) 81 Primary Cutaneous Acral CD8+ T-cell Lymphoma (Provisional) 82 Large Granular Lymphocytic Leukemia 82 T-cell Large Granular Lymphocytic Leukemia 82 Chronic Lymphoproliferative Disorder of NK Cells (Provisional) 82 T-cell Prolymphocytic Leukemia 82 NK-cell Lymphomas 83 Extranodal NK/T-cell Lymphoma, Nasal Type 83 Aggressive NK-cell Leukemia 83 EBV-positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood 83 Must Reads 84 References 84 7 Molecular Classification of the Peripheral T-cell Lymphomas 91 Tyler A. Herek and Javeed Iqbal Introduction 91 T-cell Development and Activation: An Overview 92 T-cell Receptor Signaling 92 Derivation of Diagnostic Signatures for Molecular Classification of Peripheral T-cell Lymphomas 95 Angioimmunoblastic T-cell Lymphoma and Other T Follicular Helper-derived Malignancies 95 Recurrent Genetic Features 96 Anaplastic Large-cell Lymphomas 96 Recurrent Genetic Features 96 Adult T-cell Leukemia/Lymphoma 97 Recurrent Genetic Features 97 Peripheral T-cell Lymphoma Not Otherwise Specified 97 Recurrent Genetic Features in Two Novel Subgroups 98 Hepatosplenic T-cell Lymphoma 98 Recurrent Genetic Features 98 Extranodal natural killer/T-cell Lymphoma 98 Recurrent Genetic Features 99 Cutaneous T-cell Lymphomas 99 Conclusion 99 Must Reads 99 References 99 Part III Discrete Clinical Subtypes of PTCL (Unique Epidemiology, Therapy and Management) 105 8 Peripheral T-cell Lymphoma Not Otherwise Specified 107 N. Nora Bennani and Stephen M. Ansell Introduction 107 Epidemiology, Risk Factors, and Clinical Characteristics 107 Basic Principles of Disease Biology 108 Prognostic Tools 109 Frontline Therapy 110 Management of Relapsed or Refractory Disease 111 Future Directions 112 Must Reads 112 References 112 9 Angioimmunoblastic T-cell Lymphoma 115 Jehan Dupuis and Franck Morschhauser Introduction 115 Clinical and Biological Presentation 115 Epidemiology and Risk Factors, Disease Incidence and Prevalence 117 Basic Principles of Disease Biology 118 TET2 Mutations 119 IDH2 Mutations 120 DNMT3A Mutations 120 Rho A Mutations 121 CD28 Alterations 121 Other Mutations Affecting the T-cell Lymphoma Pathway 121 Management of Disease in the Front Line 122 Management of Relapsed or Refractory Disease 122 Conventional Chemotherapy Agents 123 Bendamustine 123 Pralatrexate 123 Romidepsin 124 Belinostat 124 Newer Targeted Therapy Approaches 125 Future Directions 125 Must Reads 126 References 126 10 The Spectrum of Anaplastic Large-cell Lymphoma 129 Jianping Kong and Andrew L. Feldman Introduction 129 Epidemiology and Risk Factors 129 Disease Incidence and Prevalence 131 Basic Principles of Disease Biology 133 Management of Disease in the Front Line 134 Management of the Relapsed or Refractory Patient 137 Future Directions 138 Acknowledgement 140 Must Reads 140 References 140 11 Human T-cell Lymphotropic Virus Type 1 Positive Adult T-cell Leukemia/Lymphoma 145 Wataru Munakata and Kensei Tobinai Epidemiology and Disease Incidence 145 Basic Principles of Disease Biology 145 CCR4 and Adult T-cell Leukemia/Lymphoma 146 Clinical Features of Adult T-cell Leukemia/Lymphoma 146 Prognosis and Prognostic Index of ATLL 147 Front-line Management of Aggressive Adult T-cell Leukemia/Lymphoma 149 Chemotherapy and Hematopoietic Stem-cell Transplantation 149 Mogamulizumab with Dose-intensified Chemotherapy 150 Interferon alpha and Antiretroviral Agents 151 Chemotherapy in Transplant-ineligible Patients with Aggressive Adult T-cell Leukemia/Lymphoma 151 Front-line Management of Indolent ATLL 152 Management of Relapsed or Refractory Patients 152 Mogamulizumab Monotherapy 152 Lenalidomide Monotherapy 153 Other Treatments for Relapsed or Refractory Adult T-cell Leukemia/Lymphoma 153 Future Directions 154 Must Reads 154 References 154 12 Natural Killer/T-cell Lymphomas 159 Seok Jin Kim, Ritsuro Suzuki, Arnaud Jaccard, Soon Thye Lim and Wong Seog Kim Introduction 159 Epidemiology and Risk Factors 161 Disease Incidence and Prevalence 161 Basic Principles of Disease Biology 161 Genetic Susceptibility to NK/T-Cell Lymphoma 161 Molecular Pathogenesis 162 JAK–STAT and Associated Pathways 162 Nuclear Factor Kappa B and Other Deregulated Pathways 163 The Programmed Cell Death 1/Programmed Death Ligand 1 Pathway 163 Management of Newly Diagnosed Treatment-naïve Patients 163 Diagnosis and Initial Assessment 164 Monitoring the Response 165 Treatment Strategies 165 Localized Disease 165 Disseminated Disease 167 Consolidation Treatment with Hematopoietic Stem-cell Transplantation 167 Management of Relapsed or Refractory Disease 167 Treatment of Localized Nasal Relapse 167 Treatment of a Systemic Relapse 167 Novel Agents for Relapsed or Refractory ENKTL 168 Future Directions 168 Must Reads 168 References 169 13 T-Prolymphocytic Leukemia 175 Dima El-Sharkawi and Claire Dearden Introduction 175 Incidence 175 Clinical Features 175 Laboratory Findings 175 Treatment 176 Stem-cell Transplantation 178 Treatment for Relapsed/Refractory Disease 178 Future Directions 178 Must Reads 179 References 179 14 Large Granular Lymphocyte Leukemia 183 Karolina H. Dziewulska, Katharine B. Moosic, HeeJin Cheon, Kristine C. Olson, David J. Feith and Thomas P. Loughran, Jr Introduction 183 Epidemiology and Risk Factors 183 Prevalence of Concomitant Disorders 184 Autoimmune Diseases 184 Hematological Disorders 184 Basic Principles of Disease Biology 185 Biology 185 STAT3 Dysregulation 185 STAT3 and Common Cytopenias 186 JAK–STAT Pathway 187 Other Mutated and Dysregulated Pathways 187 Chronic Activation and Large Granular Lymphocyte Clonal Malignancy 188 STAT3 and Clonality 188 Antigenic Stimulation 188 Immune System Dysregulation 189 Cytotoxic Killer Cells and Autoimmunity 189 Humoral Abnormalities 189 Abnormal Bone Marrow 190 Neutropenia and Rheumatoid Arthritis 190 Spleen Pathology 191 Management of Disease in the Front Line 191 Diagnosis 191 Prognosis 191 Current Treatments 192 Indications for Treatment 192 Evaluation of Treatment Response 192 Therapeutic Approach 192 Canonical Immunosuppressive Treatments 192 Non-canonical Immunosuppressive Treatments 193 Supportive Therapy 194 Summary of Therapeutic Recommendations 194 Management of Relapsed or Refractory Disease 194 Future Directions 194 JAK–STAT Pathway Targeting 194 Natural Compounds 196 Other Candidate Agents 196 Funding 196 Disclosures 197 Must Reads 197 References 197 15 Gamma–Delta T-cell Lymphomas 203 Francine Foss, Aadil Ahmed and Mina Xu Introduction 203 Epidemiology and Risk Factors 203 Biology of Primary Cutaneous Gamma–Delta T-cell Lymphoma 204 Management of Disease in the Front Line 206 Management of Relapsed/Refractory Disease 208 Must Reads 209 References 209 16 Enteropathy-Associated and Monomorphic Epitheliotropic Intestinal T-cell Lymphomas 211 Craig R. Soderquist, Jennifer Shingleton, Sandeep Dave and Govind Bhagat Introduction 211 Enteropathy-associated T-cell Lymphoma 211 Epidemiology and Risk Factors 211 Disease Incidence and Prevalence 212 Basic Principles of Disease Biology 212 Morphology and Immunophenotype 212 Molecular and Genetic Alterations 212 Management of Patients in the Front Line 213 Management of the Relapsed or Refractory Patient 214 Future Directions 214 Refractory Celiac Disease 214 Disease Definition, Risk Factors, Incidence, and Prevalence 214 Basic Principles of Disease Biology 214 Morphology and Immunophenotype 214 Molecular and Genetic Alterations 215 Management of Patients in the Front-Line 216 Management of the Relapsed or Refractory Patient 216 Future Directions 216 Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma 216 Disease Risk Factors, Incidence, and Prevalence 216 Basic Principles of Disease Biology 216 Morphology and Immunophenotype 216 Molecular and Genetic Alterations 218 Management of Disease in the Front Line 218 Management of Relapsed or Refractory Disease 218 Future Directions 218 Must Reads 218 References 219 17 Hepatosplenic T-cell Lymphomas 225 Robert N. Stuver, Mwanasha Merrill and Salvia Jain Epidemiology and Disease Incidence 225 Basic Principles of Disease Biology 227 Clinical Features 227 Management of Disease in the Front Line 228 Management of the Relapsed or Refractory Disease 229 Splenectomy 230 Future Directions 230 Funding 231 Must Reads 231 References 231 18 Cutaneous T-cell Lymphoma 235 Alejandro A. Gru, Bethanie Rooke, Kevin Molloy and Julia Scarisbrick Introduction 35 Epidemiology and Risk Factors 236 Basic Principles of Disease Biology 237 Clinical, Pathologic, and Immunophenotypic Findings 240 Management of Front-Line Mycosis Fungoides/Sézary Syndrome 247 Early-stage Disease (Stages IA–IIA) 248 Late-stage Disease (Stage IIB–IVA2) 250 Stage IIB (Tumor-stage Disease) 250 Stage III–IVA1 Disease (Erythrodermic Disease and Sézary) 250 Stage IVA2–IVB Disease 250 Management of Relapsed or Refractory Disease with Mycosis Fungoides/Sézary Syndrome 250 Early-stage Disease (Stage IA–IIA) 250 Late-stage Disease (IIB–IVA2) 251 Stage IIB (Tumor-stage Disease) 251 Stage III–IVA1 (Erythrodermic Disease) 251 Stage IVA2–IVB Disease 252 Front-Line Management of Non-mycosis Fungoides Cutaneous T-cell Lymphomas 252 Management of Relapsed or Refractory Non-mycosis Fungoides Cutaneous T-cell Lymphomas 252 Future Directions 252 Must Reads 253 References 253 19 Other Rare Subtypes of Peripheral T-cell Lymphoma 259 Pier Paolo Piccaluga Introduction 259 Chronic Lymphoproliferative Disorders of Natural Killer Cells 259 Epidemiology and Risk Factors 259 Disease Incidence and Prevalence 259 Basic Principles of Disease Biology 260 Management of Front-line Disease 260 Epstein–Barr Virus-associated T-cell and NK-cell Lymphoproliferative Disorders of Childhood 260 Systemic Epstein–Barr Virus-positive T-cell Lymphoma of Childhood 260 Epidemiology and Risk Factors 260 Basic Principles of Disease Biology 260 Management of Front-Line Disease 261 Chronic Active Epstein–Barr Virus Infection of T- and NK-cell Type, Systemic Form 261 Epidemiology and Risk Factors 261 Basic Principles of Disease Biology 261 Management of Front-Line Disease 262 Chronic Active Epstein–Barr Virus Infection of T- and NK-cell Type, Cutaneous Form 264 Hydroa Vacciniforme-like Lymphoproliferative Disorder 264 Basic Principles of Disease Biology 264 Management of Disease in the Front Line 264 Severe Mosquito Bite Allergy 265 Epidemiology and Risk Factors 265 Basic Principles of Disease Biology 265 Management of Disease in the Front-Line 265 Future Directions 265 Must Reads 265 References 266 Part IV Treatment of the PTCL 269 20 Standard Front-line Therapies 271 Raphael Koch and Lorenz Truempe Introduction 271 Initial Workup and Risk Stratification 271 Front-line Therapy 274 Front-line Treatment Approaches for Common Subtypes 274 Systemic Anaplastic Large-cell Lymphomas 276 Breast Implant-associated Anaplastic Large-cell Lymphomas 277 Enteropathy-associated T-cell Lymphoma and Monomorphic Epitheliotropic Intestinal T-cell Lymphoma 277 Hepatosplenic T-cell Lymphoma 278 Extranodal natural killer/T-cell Lymphoma, Nasal Type 279 T-cell Prolymphocytic Leukemia 280 Adult T-Cell Leukemia/Lymphoma 280 Must Reads 281 References 281 21 Approved Agents in the Relapsed or Refractory Setting, Excluding Brentuximab Vedotin 287 Helen Ma and Owen A. O’Connor Introduction 287 Challenges in Developing New Drugs in Peripheral T-cell Lymphomas 288 Drugs Approved by the US Food and Drug Administration with an Indication in Relapsed/Refractory Peripheral T-cell Lymphoma 288 Pralatrexate 289 Pharmacology 289 Early-phase Data 289 Pivotal Data 289 Recent Developments 291 Histone Deacetylase Inhibitors (Including Romidepsin and Belinostat) 291 Pharmacology 291 Early Phase Data 292 Pivotal Data 292 Recent Developments 293 Drugs Approved by the US Food and Drug Administration But Without An Indication in Relapsed/Refractory Peripheral T-cell Lymphoma 294 Etoposide 294 Pharmacology 294 Clinical Experiences in Peripheral T-cell Lymphoma 294 Summary 294 Bortezomib 294 Pharmacology 294 Clinical Experiences in Peripheral T-cell Lymphoma 296 Recent Developments 296 Bendamustine 296 Pharmacology 296 Clinical Experience in Peripheral T-cell Lymphoma 296 Recent Developments 296 Gemcitabine 296 Pharmacology 296 Clinical Data 297 Recent Developments 297 Drugs Approved by International Regulatory Agencies, Not Including the United States, that Carry an Indication in Relapsed/Refractory Peripheral T-cell Lymphoma 297 Chidamide 297 Pharmacology 297 Early Phase Data 297 Pivotal Data 297 Recent Developments 297 Forodesine 297 Pharmacology 297 Early Phase Data 297 Pivotal Data 298 Recent Developments 298 Considerations in the Selection of Therapy 298 Treatment Goals 298 Aggressive Versus Indolent Disease 299 Transplant Eligible or Ineligible 299 Suitability for Chemotherapy 299 Conclusion 299 Must Reads 299 References 300 22 The Role of Autologous Stem-cell Transplantation in Peripheral T-cell Lymphomas 305 Juan Alejandro Ospina-Idárraga, Rolando Humberto Martinez-Cordero, Leonardo José Enciso-Olivera and Henry Idrobo-Quintero Introduction 305 Autologous Stem-cell Transplantation in First Complete Remission 306 Autologous Stem-cell Transplantation in Relapsed/Refractory Disease 307 Interpretation of Available Literature 307 Identifying the Most Relevant Determinants for Survival among Patients with Peripheral T-cell Lymphoma Undergoing Autologous Stem-cell Transplantation 308 Status of Response Prior to Autologous Stem-cell Transplantation 309 Risk of Stage 310 Number of Prior Therapies and Refractory Disease 311 Autologous Stem-cell Transplantation on Specific Subtypes of Peripheral T-cell Lymphoma 311 Peripheral T-cell Lymphomas Not Otherwise Specified 311 Angioimmunoblastic T Cell Lymphoma 312 Anaplastic T Large-cell Lymphoma 312 Extranodal Natural Killer/T-cell Lymphoma, Nasal Type 313 The Role of Autologous Stem-cell Transplantation in Cutaneous T-cell Lymphomas 314 Must Reads 314 References 315 23 Allogeneic Stem-cell Transplantation 319 Anna Dodero and Paolo Corradini Introduction 319 Allogeneic Stem-cell Transplantation for Relapsed and Refractory Disease (Focus on Nodal Hystotypes) 320 Allogeneic Stem-cell Transplantation as Consolidation of First Remission 322 Allogeneic Stem-cell Transplantation in Specific Subtypes 322 Cutaneous T-cell Lymphomas 322 Hepatosplenic T-cell Lymphomas 324 Extranodal Natural Killer/T-cell Lymphomas, Nasal Type 324 Adult T-cell Leukemia/Lymphoma 324 Future Directions 325 Must Reads 325 References 325 24 Emerging Immunotherapy Approaches in Peripheral T-cell Lymphomas 329 Barbara Pro and Andrei Shustov Introduction 329 Monoclonal Antibody Therapy 329 Alemtuzumab 330 Mogamulizumab 330 Immunoconjugate-Based Therapy for Peripheral T-Cell Lymphoma 331 Brentuximab Vedotin 332 Cell-Mediated or Cellular Immunotherapy in Peripheral T-Cell Lymphoma 333 PD1–PD-L1 Checkpoint Inhibition 334 AFM13 – Targeted Natural Killer Cell Immunotherapy Facilitator 335 TTI-621 – Targeted Macrophage Immunotherapy Facilitator 335 4-1BB – Enabled Adoptive Therapy of Epstein–Barr Virus-Positive Malignancies 335 IPH4102 (Anti-KIR3DL2 Monoclonal Antibody) 336 Chimeric Antigen Receptor T-cell Therapy for Peripheral T-cell Lymphoma 336 Challenges and Future Directions 336 Must Reads 337 References 338 25 Emerging New Small Molecules in Peripheral T-cell Lymphomas 343 Alessandro Broccoli and Pier Luigi Zinzani Introduction 343 Demethylating Agents 344 Janus-associated Kinase–Signal Transducers and Activators of Transcription and Spleen Tyrosine Kinase Inhibitors 345 Phosphatidylinositol 3-Kinase Inhibitors 345 Miscellaneous 347 Pro-apoptotic Small Molecules 347 Farnesyltransferase Inhibitors 347 Aurora Kinase Inhibitors 347 Conclusion 348 Must Reads 348 References 348 Part V Future Directions 351 26 The Value and Relevance of T-cell Lymphoma Registries 353 Tetiana Skrypets, Martina Manni, Monica Civallero, Iryna Kriachok and Massimo Federico Introduction 353 Population-based Cancer Registries 353 Retrospective Studies 355 T-cell Lymphoma Registries 360 T-cell Project 1.0 360 COMPLETE 363 T-cell Project 2.0 363 Future Directions 364 Disclosures 364 Must Reads 364 References 365 27 Innovative Chemotherapy-free Approaches for the Treatment of Peripheral T-Cell Lymphoma 367 Enrica Marchi, Ahmed Sawas, Helen Ma, Luigi Scotto and Francesca Montanari Introduction 367 Targeting the Peripheral T-cell Lymphoma Epigenome 369 Romidepsin Plus Pralatrexate 370 Preclinical Rationale 370 Clinical Experience 370 Romidepsin Plus 5-Azacytidine 371 Preclinical Rationale 371 Clinical Experience 371 Romidepsin Plus Duvelisib 372 Preclinical Rationale 372 Clinical Experience 372 Romidepsin Plus Lenalidomide 373 Preclinical Rationale 373 Clinical Experience 373 Panobinostat and Bortezomib 373 Preclinical Rationale 373 Clinical Experience 374 A Glance at the Future: Building on the Active Doublets 374 Must Reads 375 References 375 28 Global Collaborations 379 Dejan Radjeski, Eliza Hawke, Owen A. O’Connor, Pier Luigi Zinzani, Won Seog Kim and Enrica Marchi Introduction 379 The Global T-cell Lymphoma Consortium 380 The Mission 380 Structure 380 Organizational Features 380 Submission of Trial Concepts 381 Budget Negotiations 382 Institutional Review Board 383 Publications 383 Conclusion 384 Index 385

Autorenportrait

About the Editors Owen A. O’Connor, American Cancer Society Research Professor, Professor of Medicine, Department of Medicine, Division of Hematology and Oncology, Program for T-cell Lymphoma Research, Department of Microbiology, Immunology, and Cancer Research, University of Virginia Cancer Center, Charlottesville, VA, USA. Won Seog Kim, MD, PhD is Professor of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Pier Luigi Zinzani, MD, PhD is Professor of Hematology, Director of Lymphoma and CLL Unit, and Chief of Phase I clinical trials, Institute of Hematology, University of Bologna, Italy.

Back cover copy

Provides a comprehensive look at Peripheral T-Cell lymphomas, including the group’s unique geographic distribution, underlying genetics, and novel treatments Peripheral T-Cell lymphomas (PTCL) are a diverse group of lymphoid malignancies that develop from mature T cells and natural killer (NK) cells. PTCL represent 10-15% of all cases of non-Hodgkin lymphoma in the US, and up to 20-25% of cases in South America, Asia, and other regions around the world. The role of different etiologic factors and the variation of geographic distribution makes PTCL one of the most difficult types of cancer to understand and treat. For the first time in a single volume, The Peripheral T-Cell Lymphomas presents a comprehensive survey of this complex and rare group of blood cancers. Featuring contributions from an international team of leading authorities in the various aspects of PTCL, this authoritative text covers biology, epidemiology, classification, approved and emerging drugs, molecular genetics, and more. Detailed clinical chapters address diagnosis, prognosis, and treatment of each of the major PTCL subtypes identified in the 2018 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. This much-needed resource: <ul><li>Covers the biological basis, epidemiology, classification, and treatment of PTCL</li><li>Discusses the future of the field, including global collaboration efforts and novel approaches to PCTL</li><li>Explores the role of biologics in PTCL and autologous and allogeneic stem-cell transplantation</li><li>Offers new insights on molecular pathogenesis, innovative therapeutics, and novel drug combinations</li><li>Features contributions from the Chairs The T-Cell Lymphoma Forum: the world’s largest meeting focused on PTCL</li></ul> Reflecting the unique epidemiology and genetic diversity of the PTCL, The Peripheral T-Cell Lymphomas is an indispensable source of data, insight, and references for the medical community, particularly oncologists and hematologists in both training and practice.