Оглавление
Группа авторов. The Peripheral T-Cell Lymphomas
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
The Peripheral T‐Cell Lymphomas
Contributors
About the Companion Website
1 The Fundamentals of T‐cell Lymphocyte Biology
TAKE HOME MESSAGES
Introduction
General View of the Differentiation and Function of T Lymphocytes
The T‐cell System as a Frame for Peripheral T‐cell Lymphoma: Taking Plasticity into Account
Must Reads
References
2 Mechanisms of T‐cell Lymphomagenesis
TAKE HOME MESSAGES
Introduction
Oncogenic Events in the Transformation of T or Natural Killer Cells. Genetic Lesions
Deregulated Pathways in Peripheral T‐cell Lymphoma Oncogenesis (Figure 2.1, Table 2.1) Epigenetic Regulation
Signaling Pathways
Cell‐cycle Control
Immune Surveillance
Role of the Microenvironment in Peripheral T‐cell Lymphoma
The Model of Angio‐immunoblastic T‐cell Lymphoma and T Follicular Helper‐derived Peripheral T‐cell Lymphoma
Crosstalk Between Neoplastic T Follicular Helper Cells and Their Microenvironment in Angioimmunoblastic T‐cell Lymphoma
Genetic Alterations in the Angioimmunoblastic T‐cell Lymphoma Microenvironment
Specific Microenvironment Components Present in Other Primary Cutaneous T‐cell Lymphoma Entities
Macrophages
Angiogenesis
Eosinophils
Underlying Factors Favoring the Tumor Transformation
Viruses
Human T‐cell Leukemia Virus Type 1
Epstein–Barr Virus
Chronic Antigenic Stimulation
Other Factors
Cell of Origin (Table 2.1)
Conclusion
Acknowledgement
Must Reads
References
3 Epigenetics of T‐cell Lymphoma
TAKE HOME MESSAGES
Introduction
Epigenetic Pathways Altered in T‐cell Lymphoma
Epigenetic Changes Within Specific T‐cell Lymphoma Subtypes
Peripheral T‐cell Lymphoma Not Otherwise Specified
Angioimmunoblastic T‐cell Lymphoma and Peripheral T‐cell Lymphoma with T Follicular Helper Phenotype
Anaplastic Large‐cell Lymphoma
Adult T‐cell Leukemia/Lymphoma
Intestinal T‐cell Lymphoma
Hepatosplenic T‐cell Lymphomas
Extranodal Natural Killer/T‐cell Lymphoma
Mycosis Fungoides and Sézary Syndrome
Established and Emerging Drugs Targeting the T‐cell Lymphoma Epigenome
DNA Methyltransferase Inhibitors
Isocitrate Dehydrogenase Inhibitors
EZH2 Inhibitors
BET Inhibitors
Protein Arginine Methyltransferases Inhibitors
Combination Therapies Involving Epigenetic Targeting Agents
Future Directions
Must Reads
References
4 Animal Models of T‐cell Lymphoma
TAKE HOME MESSAGES
Introduction
Angioimmunoblastic T‐cell Lymphoma
The ROQUIN Mouse Model
The Mouse Models Recapitulating Human Angioimmunoblastic T‐cell Lymphoma Genomic Features
Tet2 Gene Trap Mice
G17V RHOA Mouse Model
PDX Models of Angioimmunoblastic T‐cell Lymphoma
Anaplastic Large T‐cell Lymphoma
Viral and Chimeric Models
Transgenic Models
CRISPR‐Based Models
PDX Models of Anaplastic Large‐Cell Lymphomas
Human T‐cell Lymphotropic Virus Type 1 Adult T‐cell Leukemia/Lymphoma
Mice Expressing HTLV‐1 Viral Proteins
PDX Models of Adult T‐cell Leukemia/Lymphoma
Cutaneous T‐cell Lymphoma
Enteropathy‐associated T‐cell Lymphoma
Conclusion
Must Reads
References
5 Geographic Distribution of the Peripheral T‐cell Lymphomas: Global Epidemiology
TAKE HOME MESSAGES
Historical Perspective
Epidemiology
Peripheral T‐cell Lymphoma, Not Otherwise Specified
Angioimmunoblastic T‐cell Lymphoma
Anaplastic Large‐cell Lymphoma
Adult T‐cell Lymphoma/Leukemia(HTLV Associated)
Extranodal NK/T‐cell Lymphomas
T‐cell Prolymphocytic Leukemia
Large Granular Lymphocytic Leukemia
Primary Cutaneous Gamma/Delta PTCL
Enteropathy Associated T‐cell Lymphomas and Monomorphic Epitheliotropic Intestinal T‐cell lymphoma
Hepatosplenic T‐cell Lymphoma
The Cutaneous T‐cell Lymphomas
Conclusion
Must Reads
References
5.A 2017 World Health Organization Classification of Mature T- and NK-cell Neoplasms
6 Classification of the Peripheral T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Angioimmunoblastic T‐cell Lymphoma and Other Nodal Lymphomas of T follicular Helper Cell Origin
Angioimmunoblastic T‐cell Lymphoma
Follicular T‐cell Lymphoma
Nodal Peripheral T‐cell Lymphoma with T‐follicular Helper Phenotype
Peripheral T‐cell Lymphoma Not Otherwise Specified
Anaplastic Large‐cell Lymphomas
Anaplastic Large‐cell Lymphoma, ALK‐Positive
Anaplastic Large‐cell Lymphoma, ALK‐Negative
Breast Implant‐associated Anaplastic Large‐cell Lymphoma (Provisional)
Adult T‐cell Leukemia/Lymphoma
Intestinal T‐cell Lymphomas
Enteropathy‐associated T‐Cell Lymphoma
Monomorphic Epitheliotropic Intestinal T‐cell Lymphoma
Intestinal T‐cell ymphoma, Not Otherwise Specified
Indolent T‐cell Lymphoproliferative Disorder of the Gastrointestinal Tract (Provisional)
NK‐Cell Enteropathy
Hepatosplenic T‐cell Lymphoma
Mycosis Fungoides
Sézary Syndrome
Primary Cutaneous CD30‐positive T‐cell Lymphoproliferative Disorders
Lymphomatoid Papulosis
Primary Cutaneous Anaplastic Large‐cell Lymphoma
Subcutaneous Panniculitis‐like T‐cell Lymphoma
Primary Cutaneous Gamma–Delta T‐cell Lymphoma
Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T‐cell Lymphoma (Provisional)
Primary Cutaneous CD4+ Small/Medium T‐Cell Lymphoproliferative Disorder (Provisional)
Primary Cutaneous Acral CD8+ T‐cell Lymphoma (Provisional)
Large Granular Lymphocytic Leukemia
T‐cell Large Granular Lymphocytic Leukemia
Chronic Lymphoproliferative Disorder of NK Cells (Provisional)
T‐cell Prolymphocytic Leukemia
NK‐cell Lymphomas
Extranodal NK/T‐cell Lymphoma, Nasal Type
Aggressive NK‐cell Leukemia
EBV‐positive T‐cell and NK‐cell Lymphoproliferative Diseases of Childhood
Must Reads
References
7 Molecular Classification of the Peripheral T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
T‐cell Development and Activation: An Overview
T‐cell Receptor Signaling
Derivation of Diagnostic Signatures for Molecular Classification of Peripheral T‐cell Lymphomas
Angioimmunoblastic T‐cell Lymphoma and Other T Follicular Helper‐derived Malignancies
Recurrent Genetic Features
Anaplastic Large‐cell Lymphomas
Recurrent Genetic Features
Adult T‐cell Leukemia/Lymphoma
Recurrent Genetic Features
Peripheral T‐cell Lymphoma Not Otherwise Specified
Recurrent Genetic Features in Two Novel Subgroups
Hepatosplenic T‐cell Lymphoma
Recurrent Genetic Features
Extranodal natural killer/T‐cell Lymphoma
Recurrent Genetic Features
Cutaneous T‐cell Lymphomas
Conclusion
Must Reads
References
8 Peripheral T‐cell Lymphoma Not Otherwise Specified
TAKE HOME MESSAGES
Introduction
Epidemiology, Risk Factors, and Clinical Characteristics
Basic Principles of Disease Biology
Prognostic Tools
Frontline Therapy
Management of Relapsed or Refractory Disease
Future Directions
Must Reads
References
9 Angioimmunoblastic T‐cell Lymphoma
TAKE HOME MESSAGES
Introduction
Clinical and Biological Presentation
Epidemiology and Risk Factors, Disease Incidence and Prevalence
Basic Principles of Disease Biology
TET2 Mutations
IDH2 Mutations
DNMT3A Mutations
Rho A Mutations
CD28 Alterations
Other Mutations Affecting the T‐cell Lymphoma Pathway
Management of Disease in the Front Line
Management of Relapsed or Refractory Disease
Conventional Chemotherapy Agents
Bendamustine
Pralatrexate
Romidepsin
Belinostat
Newer Targeted Therapy Approaches
Future Directions
Must Reads
References
10 The Spectrum of Anaplastic Large‐cell Lymphoma
TAKE HOME MESSAGES
Introduction
Epidemiology and Risk Factors
Disease Incidence and Prevalence
Basic Principles of Disease Biology
Management of Disease in the Front Line
Management of the Relapsed or Refractory Patient
Future Directions
Acknowledgement
Must Reads
References
11 Human T‐cell Lymphotropic Virus Type 1 Positive Adult T‐cell Leukemia/Lymphoma
TAKE HOME MESSAGES
Epidemiology and Disease Incidence
Basic Principles of Disease Biology
CCR4 and Adult T‐cell Leukemia/Lymphoma
Clinical Features of Adult T‐cell Leukemia/Lymphoma
Prognosis and Prognostic Index of ATLL
Front‐line Management of Aggressive Adult T‐cell Leukemia/Lymphoma. Chemotherapy and Hematopoietic Stem‐cell Transplantation
Mogamulizumab with Dose‐intensified Chemotherapy
Interferon alpha and Antiretroviral Agents
Chemotherapy in Transplant‐ineligible Patients with Aggressive Adult T‐cell Leukemia/Lymphoma
Front‐line Management of Indolent ATLL
Management of Relapsed or Refractory Patients. Mogamulizumab Monotherapy
Lenalidomide Monotherapy
Other Treatments for Relapsed or Refractory Adult T‐cell Leukemia/Lymphoma
Future Directions
Must Reads
References
12 Natural Killer/T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Epidemiology and Risk Factors
Disease Incidence and Prevalence
Basic Principles of Disease Biology
Genetic Susceptibility to NK/T‐Cell Lymphoma
Molecular Pathogenesis
JAK–STAT and Associated Pathways
Nuclear Factor Kappa B and Other Deregulated Pathways
The Programmed Cell Death 1/Programmed Death Ligand 1 Pathway
Management of Newly Diagnosed Treatment‐naïve Patients
Diagnosis and Initial Assessment
Monitoring the Response
Treatment Strategies
Localized Disease
Disseminated Disease
Consolidation Treatment with Hematopoietic Stem‐cell Transplantation
Management of Relapsed or Refractory Disease
Treatment of Localized Nasal Relapse
Treatment of a Systemic Relapse
Novel Agents for Relapsed or Refractory ENKTL
Future Directions
Must Reads
References
13 T‐Prolymphocytic Leukemia
TAKE HOME MESSAGES
Introduction. Incidence
Clinical Features
Laboratory Findings
Treatment
Stem‐cell Transplantation
Treatment for Relapsed/Refractory Disease
Future Directions
Must Reads
References
14 Large Granular Lymphocyte Leukemia
TAKE HOME MESSAGES
Introduction
Epidemiology and Risk Factors
Prevalence of Concomitant Disorders
Autoimmune Diseases
Hematological Disorders
Basic Principles of Disease Biology. Biology
STAT3 Dysregulation
STAT3 and Common Cytopenias
JAK–STAT Pathway
Other Mutated and Dysregulated Pathways
Chronic Activation and Large Granular Lymphocyte Clonal Malignancy
STAT3 and Clonality
Antigenic Stimulation
Immune System Dysregulation
Cytotoxic Killer Cells and Autoimmunity
Humoral Abnormalities
Abnormal Bone Marrow
Neutropenia and Rheumatoid Arthritis
Spleen Pathology
Management of Disease in the Front Line. Diagnosis
Prognosis
Current Treatments. Indications for Treatment
Evaluation of Treatment Response
Therapeutic Approach
Canonical Immunosuppressive Treatments
Non‐canonical Immunosuppressive Treatments
Supportive Therapy
Summary of Therapeutic Recommendations
Management of Relapsed or Refractory Disease
Future Directions
JAK–STAT Pathway Targeting
Natural Compounds
Other Candidate Agents
Funding
Disclosures
Must Reads
References
15 Gamma–Delta T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Epidemiology and Risk Factors
Biology of Primary Cutaneous Gamma–Delta T‐cell Lymphoma
Management of Disease in the Front Line
Management of Relapsed/Refractory Disease
Must Reads
References
16 Enteropathy‐Associated and Monomorphic Epitheliotropic Intestinal T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Enteropathy‐associated T‐cell Lymphoma. Epidemiology and Risk Factors
Disease Incidence and Prevalence
Basic Principles of Disease Biology
Morphology and Immunophenotype
Molecular and Genetic Alterations
Management of Patients in the Front Line
Management of the Relapsed or Refractory Patient
Future Directions
Refractory Celiac Disease. Disease Definition, Risk Factors, Incidence, and Prevalence
Basic Principles of Disease Biology
Morphology and Immunophenotype
Molecular and Genetic Alterations
Management of Patients in the Front‐Line
Management of the Relapsed or Refractory Patient
Future Directions
Monomorphic Epitheliotropic Intestinal T‐Cell Lymphoma. Disease Risk Factors, Incidence, and Prevalence
Basic Principles of Disease Biology
Morphology and Immunophenotype
Molecular and Genetic Alterations
Management of Disease in the Front Line
Management of Relapsed or Refractory Disease
Future Directions
Must Reads
References
17 Hepatosplenic T‐cell Lymphomas
TAKE HOME MESSAGES
Epidemiology and Disease Incidence
Basic Principles of Disease Biology
Clinical Features
Management of Disease in the Front Line
Management of the Relapsed or Refractory Disease
Splenectomy
Future Directions
Funding
Must Reads
References
18 Cutaneous T‐cell Lymphoma
TAKE HOME MESSAGES
Introduction
Epidemiology and Risk Factors
Basic Principles of Disease Biology
Clinical, Pathologic, and Immunophenotypic Findings
Management of Front‐Line Mycosis Fungoides/Sézary Syndrome
Early‐stage Disease (Stages IA–IIA)
Late‐stage Disease (Stage IIB–IVA2) Stage IIB (Tumor‐stage Disease)
Stage III–IVA1 Disease (Erythrodermic Disease and Sézary)
Stage IVA2–IVB Disease
Management of Relapsed or Refractory Disease with Mycosis Fungoides/Sézary Syndrome. Early‐stage Disease (Stage IA–IIA)
Late‐stage Disease (IIB–IVA2) Stage IIB (Tumor‐stage Disease)
Stage III–IVA1 (Erythrodermic Disease)
Stage IVA2–IVB Disease
Front‐Line Management of Non‐mycosis Fungoides Cutaneous T‐cell Lymphomas
Management of Relapsed or Refractory Non‐mycosis Fungoides Cutaneous T‐cell Lymphomas
Future Directions
Must Reads
References
19 Other Rare Subtypes of Peripheral T‐cell Lymphoma
TAKE HOME MESSAGES
Introduction
Chronic Lymphoproliferative Disorders of Natural Killer Cells. Epidemiology and Risk Factors
Disease Incidence and Prevalence
Basic Principles of Disease Biology
Management of Front‐line Disease
Epstein–Barr Virus‐associated T‐cell and NK‐cell Lymphoproliferative Disorders of Childhood
Systemic Epstein–Barr Virus‐positive T‐cell Lymphoma of Childhood. Epidemiology and Risk Factors
Basic Principles of Disease Biology
Management of Front‐Line Disease
Chronic Active Epstein–Barr Virus Infection of T‐ and NK‐cell Type, Systemic Form. Epidemiology and Risk Factors
Basic Principles of Disease Biology
Management of Front‐Line Disease
Chronic Active Epstein–Barr Virus Infection of T‐ and NK‐cell Type, Cutaneous Form
Hydroa Vacciniforme‐like Lymphoproliferative Disorder. Epidemiology and Risk Factors
Basic Principles of Disease Biology
Management of Disease in the Front Line
Severe Mosquito Bite Allergy. Epidemiology and Risk Factors
Basic Principles of Disease Biology
Management of Disease in the Front‐Line
Future Directions
Must Reads
References
20 Standard Front‐line Therapies
TAKE HOME MESSAGES
Introduction
Initial Workup and Risk Stratification
Front‐line Therapy
Front‐line Treatment Approaches for Common Subtypes
Systemic Anaplastic Large‐cell Lymphomas
Breast Implant‐associated Anaplastic Large‐cell Lymphomas
Enteropathy‐associated T‐cell Lymphoma and Monomorphic Epitheliotropic Intestinal T‐cell Lymphoma
Hepatosplenic T‐cell Lymphoma
Extranodal natural killer/T‐cell Lymphoma, Nasal Type
T‐cell Prolymphocytic Leukemia
Adult T‐Cell Leukemia/Lymphoma
Must Reads
References
21 Approved Agents in the Relapsed or Refractory Setting, Excluding Brentuximab Vedotin
TAKE HOME MESSAGES
Introduction
Challenges in Developing New Drugs in Peripheral T‐cell Lymphomas
Drugs Approved by the US Food and Drug Administration with an Indication in Relapsed/Refractory Peripheral T‐cell Lymphoma
Pralatrexate. Pharmacology
Early‐phase Data
Pivotal Data
Recent Developments
Histone Deacetylase Inhibitors (Including Romidepsin and Belinostat) Pharmacology
Early Phase Data
Pivotal Data
Recent Developments
Drugs Approved by the US Food and Drug Administration But Without An Indication in Relapsed/Refractory Peripheral T‐cell Lymphoma
Etoposide. Pharmacology
Clinical Experiences in Peripheral T‐cell Lymphoma
Summary
Bortezomib. Pharmacology
Clinical Experiences in Peripheral T‐cell Lymphoma
Recent Developments
Bendamustine. Pharmacology
Clinical Experience in Peripheral T‐cell Lymphoma
Recent Developments
Gemcitabine. Pharmacology
Clinical Data
Recent Developments
Drugs Approved by International Regulatory Agencies, Not Including the United States, that Carry an Indication in Relapsed/Refractory Peripheral T‐cell Lymphoma. Chidamide. Pharmacology
Early Phase Data
Pivotal Data
Recent Developments
Forodesine. Pharmacology
Early Phase Data
Pivotal Data
Recent Developments
Considerations in the Selection of Therapy
Treatment Goals
Aggressive Versus Indolent Disease
Transplant Eligible or Ineligible
Suitability for Chemotherapy
Conclusion
Must Reads
References
22 The Role of Autologous Stem‐cell Transplantation in Peripheral T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Autologous Stem‐cell Transplantation in First Complete Remission
Autologous Stem‐cell Transplantation in Relapsed/Refractory Disease
Interpretation of Available Literature
Identifying the Most Relevant Determinants for Survival among Patients with Peripheral T‐cell Lymphoma Undergoing Autologous Stem‐cell Transplantation
Status of Response Prior to Autologous Stem‐cell Transplantation
Risk of Stage
Number of Prior Therapies and Refractory Disease
Autologous Stem‐cell Transplantation on Specific Subtypes of Peripheral T‐cell Lymphoma. Peripheral T‐cell Lymphomas Not Otherwise Specified
Angioimmunoblastic T Cell Lymphoma
Anaplastic T Large‐cell Lymphoma
Extranodal Natural Killer/T‐cell Lymphoma, Nasal Type
The Role of Autologous Stem‐cell Transplantation in Cutaneous T‐cell Lymphomas
Must reads
References
23 Allogeneic Stem‐cell Transplantation
TAKE HOME MESSAGES
Introduction
Allogeneic Stem‐cell Transplantation for Relapsed and Refractory Disease (Focus on Nodal Hystotypes)
Allogeneic Stem‐cell Transplantation as Consolidation of First Remission
Allogeneic Stem‐cell Transplantation in Specific Subtypes. Cutaneous T‐cell Lymphomas
Hepatosplenic T‐cell Lymphomas
Extranodal Natural Killer/T‐cell Lymphomas, Nasal Type
Adult T‐cell Leukemia/Lymphoma
Future Directions
Must Reads
References
24 Emerging Immunotherapy Approaches in Peripheral T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Monoclonal Antibody Therapy
Alemtuzumab
Mogamulizumab
Immunoconjugate‐Based Therapy for Peripheral T‐Cell Lymphoma
Brentuximab Vedotin
Cell‐Mediated or Cellular Immunotherapy in Peripheral T‐Cell Lymphoma
PD1–PD‐L1 Checkpoint Inhibition
AFM13 – Targeted Natural Killer Cell Immunotherapy Facilitator
TTI‐621 – Targeted Macrophage Immunotherapy Facilitator
4‐1BB – Enabled Adoptive Therapy of Epstein–Barr Virus‐Positive Malignancies
IPH4102 (Anti‐KIR3DL2 Monoclonal Antibody)
Chimeric Antigen Receptor T‐cell Therapy for Peripheral T‐cell Lymphoma
Challenges and Future Directions
Must Reads
References
25 Emerging New Small Molecules in Peripheral T‐cell Lymphomas
TAKE HOME MESSAGES
Introduction
Demethylating Agents
Janus‐associated Kinase–Signal Transducers and Activators of Transcription and Spleen Tyrosine Kinase Inhibitors
Phosphatidylinositol 3‐Kinase Inhibitors
Miscellaneous. Pro‐apoptotic Small Molecules
Farnesyltransferase Inhibitors
Aurora Kinase Inhibitors
Conclusion
Must Reads
References
26 The Value and Relevance of T‐cell Lymphoma Registries
TAKE HOME MESSAGES
Introduction
Population‐based Cancer Registries
Retrospective Studies
T‐cell Lymphoma Registries
T‐cell Project 1.0
COMPLETE
T‐cell Project 2.0
Future Directions
Disclosures
Must Reads
References
27 Innovative Chemotherapy‐free Approaches for the Treatment of Peripheral T‐Cell Lymphoma
TAKE HOME MESSAGES
Introduction
Targeting the Peripheral T‐cell Lymphoma Epigenome
Romidepsin Plus Pralatrexate. Preclinical Rationale
Clinical Experience
Romidepsin Plus 5‐Azacytidine. Preclinical Rationale
Clinical Experience
Romidepsin Plus Duvelisib. Preclinical Rationale
Clinical Experience
Romidepsin Plus Lenalidomide. Preclinical Rationale
Clinical Experience
Panobinostat and Bortezomib. Preclinical Rationale
Clinical Experience
A Glance at the Future: Building on the Active Doublets
Must Reads
References
28 Global Collaborations
Introduction
The Global T‐cell Lymphoma Consortium
The Mission
Structure
Organizational Features
Submission of Trial Concepts
Budget Negotiations
Institutional Review Board
Publications
Conclusion
Index. a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
r
s
t
u
v
w
WILEY END USER LICENSE AGREEMENT
