Indolent Lymphomas (Hematologic Malignancies)

✍ Scribed by Martin Dreyling (editor), Marco Ladetto (editor)

• Publisher: Springer
• Year: 2021
• Tongue: English
• Leaves: 244
• Category: Library

✦ Synopsis

This book provides a comprehensive overview of current treatment strategies in indolent lymphomas, the clinical management of which continues to pose significant challenges for the general oncologist despite the tremendous progress in diagnosis, evaluation of risk factors, and molecular targeted approaches. Experts in the field from around the world describe the histomorphology in a clinically relevant manner, consider the role of risk factors in detail, and discuss the full spectrum of therapeutic approaches. Special emphasis is placed on the translation of molecular science into clinical care, and a disease-specific algorithm is proposed for each entity. The coverage encompasses follicular lymphoma, MALT, nodal marginal zone lymphoma, splenic marginal zone lymphoma, Waldenström’s macroglobulinemia, hairy cell leukemia, chronic lymphocytic leukemia, mycosis fungoides, large granular lymphocytic leukemia, and also mantle cell lymphoma. The book will be an excellent resource for experienced and inexperienced practitioners alike.

✦ Table of Contents

Contents
1: The General Pathology
1.1 Introduction
1.1.1 What Are Indolent Lymphomas?
1.1.2 General Considerations on Indolent NHL Diagnostics
1.1.2.1 Technical Issues
1.1.2.2 Anatomic Issues
Reference
2: Molecular Genetics in Indolent Lymphomas
2.1 Introduction
2.2 The Molecular Biology of Indolent Lymphomas: Follicular Lymphoma as a Prototypical Example
2.2.1 The Translocation t (14;18) in FL
2.2.2 Recurrent Genetic Alterations in FL
2.2.3 Mutations in Epigenetic Regulators
2.2.4 Molecular Genetics and the Role of the Tumor Microenvironment
2.2.5 Histological Transformation of Follicular Lymphoma
2.2.6 Classifying Mutations
2.2.7 Temporal and Spatial Evolution in FL and Evidence for a Common Progenitor Cell (CPC)
2.3 Molecular Genetics in Indolent Lymphomas: A Clinical Perspective
2.3.1 Follicular Lymphoma
2.3.2 Marginal Zone Lymphoma (MZL)
2.3.3 Waldenström’s Macroglobulinemia
2.3.4 Mantle Cell Lymphoma (MCL)
2.3.5 Hairy Cell Leukemia (HCL)
2.3.6 Chronic Lymphocytic Leukemia
2.3.7 Indolent T-Cell Lymphomas
2.4 Perspective
References
3: Minimal Residual Disease (MRD) in Indolent Lymphomas
3.1 Introduction
3.2 Methods for MRD Determination
3.2.1 MRD Detection by FC
3.2.2 MRD Detection by PCR-Based Methods
3.2.3 MRD Detection by Next-Generation Sequencing
3.3 MRD in Follicular Lymphoma and Other Indolent Lymphomas
3.4 MRD in Mantle Cell Lymphoma
3.5 MRD in Chronic Lymphocytic Leukemia
3.6 Integrating MRD and Imaging Tools
3.7 Future Perspectives
References
4: PET Imaging
4.1 Introduction
4.2 PET in Staging
4.3 PET Response Assessment
4.3.1 Interim PET
4.3.2 End-of-Induction Assessment
4.3.2.1 PET Response
4.4 PET in Other Indolent B-Cell Lymphomas
4.5 Conclusion
References
5: Role of Radiotherapy
5.1 Introduction
5.2 Evolution of Modern Lymphoma Radiotherapy
5.3 Radiotherapy in Indolent Lymphomas
5.3.1 Early-Stage Nodal Indolent Lymphomas
5.3.1.1 Follicular Lymphoma
5.3.1.2 Mantle Cell Lymphoma
5.3.1.3 Nodal Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma, Small Lymphocytic Lymphoma
5.3.2 Early-Stage Extranodal Indolent Lymphomas
5.3.2.1 Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma
5.3.2.2 Cutaneous Lymphoma
5.3.3 Nodal Indolent Lymphoma, Advanced Disease
5.4 Conclusion
References
Part I: B-Cell Lymphoma
6: Follicular Lymphoma
6.1 Introduction
6.2 Epidemiology
6.3 Pathology
6.4 Immunophenotype and molecular markers
6.5 Pathological Variants
6.6 Staging
6.7 Clinical Presentation
6.8 Risk Stratification and Prognosis
6.9 First-Line Treatment
6.10 Initial Treatment of Limited-Stage FL
6.11 Initial Treatment of Advanced-Stage FL
6.11.1 Advanced-Stage FL with Low Tumor Burden
6.11.2 Advanced-Stage FL with High Tumor Burden
6.11.3 The Role of Maintenance Therapy
6.12 The Role of High-Dose Chemotherapy and Autologous Stem-Cells Transplant
6.13 The Role of Allogeneic Stem Cell Transplantation
6.14 Radioimmunotherapy (RIT)
6.15 Management of Relapsed FL
6.16 Novel Agents in the Management of FL
6.16.1 Lenalidomide
6.16.2 Phosphatidylinositol 3-Kinases (PI3K) Inhibitors
6.16.3 Bruton’s Tyrosine Kinase Inhibitors
6.16.4 Epigenetic Therapies
6.16.5 Antibody–Drug Conjugates
6.16.6 Bcl-2 Inhibitors
6.17 Conclusions
References
7: Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)
7.1 Introduction
7.2 Pathology and Pathogenesis of MALT Lymphoma
7.2.1 Morphology
7.2.2 Genetics of MALT Lymphoma
7.2.3 Pathogenesis of MALT Lymphoma
7.2.4 Infectious Agents and MALT Lymphoma
7.2.5 Autoimmune Disorders
7.3 Clinical Presentation, Diagnosis and Staging
7.3.1 Diagnostic Procedures for Gastric MALT Lymphoma
7.3.2 Staging Systems
7.3.3 Prognostic Factors
7.4 Treatment of MALT Lymphoma
7.4.1 Anti-infective Therapy
7.4.2 Local Therapy
7.4.3 Systemic Therapies
7.4.4 Alkylating Agents and Combinations
7.4.5 The IELSG19 Phase III Trial
7.4.6 Bendamustine
7.5 Nucleoside Analogues
7.6 Immunotherapy and Immunomodulatory Agents
7.6.1 Rituximab
7.6.2 IMiDs
7.6.2.1 Clarithromycin
7.6.3 Radio-Immunotherapy (90-Y-Ibritumomab-Tiuxetan)
7.7 Conclusion
References
8: Nodal Marginal Zone Lymphoma
8.1 Definition
8.2 Pathogenesis
8.3 Histologic and Biologic Characteristics
8.4 Prognosis
8.5 First-Line Treatment
8.6 Treatment of Relapse and New Options
8.7 Summary
References
9: Splenic Marginal Zone Lymphoma
9.1 Epidemiology
9.2 Clinical Manifestation
9.3 Peripheral Blood Cytology
9.4 Bone Marrow
9.5 Spleen
9.6 Immunophenotype
9.7 Genetic and Biomolecular Landscape
9.8 Diagnosis
9.9 Staging and Prognostic Scores
9.10 Therapy
9.11 Watchful Waiting
9.12 HCV Antiviral Treatment
9.13 Who Needs Anti-neoplastic Treatment?
9.14 Splenectomy
9.15 Chemotherapy
9.16 Rituximab Monotherapy
9.17 Chemoimmunotherapy
References
10: Waldenstrom’s Macroglobulinemia
10.1 Epidemiology
10.2 Clinical Features
10.3 Morbidity Mediated by the Physicochemical Properties of IgM
10.3.1 Hyperviscosity Syndrome
10.3.2 Type I Cryoglobulinemia
10.3.3 Tissue Deposition
10.3.4 Interaction with Circulating Proteins
10.4 Morbidity Mediated by the Immunological Effects of IgM
10.4.1 Autoantibody Activity
10.4.2 Type II Cryoglobulinemia
10.4.3 IgM-Related Neuropathy
10.4.4 Cold Agglutinin Hemolytic Anemia
10.5 Manifestations Related to Tissue Infiltration by Neoplastic Cells
10.6 Laboratory Investigations and Findings
10.6.1 Laboratory Assessment
10.6.2 Genomic Features
10.6.3 Serum Viscosity
10.6.4 Prognosis
10.7 Treatment of Waldenström’s Macroglobulinemia
10.7.1 Asymptomatic Patients
10.7.2 Treatment Options
10.7.3 Immunochemotherapy
10.7.3.1 DRC
10.7.3.2 Rituximab-Bendamustine (B-R)
10.7.3.3 Bortezomib
10.7.4 Chemotherapy-Free Approaches
10.7.4.1 Rituximab
10.7.4.2 BTK Inhibitors
10.7.5 Maintenance Therapy
10.8 High-Dose Therapy and Stem Cell Transplantation
10.9 Future Developments
References
11: Mantle Cell Lymphoma
11.1 Definition and Epidemiology
11.2 Histology and Immunophenotype
11.3 Pathogenesis, Cytogenetics, and Molecular Genetics
11.4 Prognostic Factors
11.5 Clinical Presentation
11.6 Diagnosis and Differential Diagnosis
11.7 Therapy
11.7.1 Localized Stage
11.7.2 Advanced Stage
11.7.2.1 Conventional Chemotherapy
11.7.2.2 Combined Immunochemotherapy
11.7.2.3 Therapy in Patients ≤65 years
Induction: Dose-Intensified, Cytarabine-Containing Regimen
Consolidation: Autologous Stem Cell Transplantation
Maintenance
Radioimmunotherapy
11.7.2.4 Therapy in Patients >65 Years
Induction
Maintenance
11.7.3 Recurrent and Refractory Disease
11.7.3.1 Allogenic Transplantation
11.7.3.2 Molecular Targeted Therapies
11.8 Outlook
References
12: Hairy Cell Leukemia
12.1 Introduction
12.2 Epidemiology
12.3 Molecular Biology and Pathogenesis
12.4 Differential Diagnosis
12.5 Prognosis
12.6 Treatment Response Evaluation and Disease Progression
12.7 Treatment of Newly Diagnosed Patients with Classic HCL
12.8 Treatment of Relapsed and Refractory Patients with Classic HCL
12.9 Treatment of Hairy Cell Leukemia Variant
12.10 Novel Agents
12.11 Treatment Complications and Supportive Care
12.12 Conclusions
References
13: Treatment of Chronic Lymphocytic Leukemia
13.1 Treatment
13.1.1 Indication for Treatment Initiation
13.1.2 General Considerations for the Choice of Therapy
13.2 Frontline Treatment
13.2.1 Treatment of Fit Patients
13.2.2 Treatment of Less Fit Patients
13.3 Conclusion
13.4 Relapse Treatment
13.4.1 Management of Late Relapsed Patients After Chemoimmunotherapy
13.4.2 Inhibitors of the B-Cell Receptor Pathway to Treat r/r Patients
13.4.3 BCL-2 Antagonists in r/r CLL
13.4.4 Treatment of After Therapy Discontinuation of Targeted Agents
13.4.5 Investigational Drugs in r/r Disease
13.4.6 Allogenic Stem Cell Transplantation in r/r Disease
13.5 Conclusion of Relapse Treatment
13.6 Outlook to Future Combinations
References
Part II: T-Cell Lymphoma
14: Indolent Cutaneous T-Cell Lymphomas
14.1 Introduction
14.2 Mycosis Fungoides
14.2.1 Clinical Features
14.2.2 Histopathology
14.2.3 Treatment
14.2.4 Prognosis and Predictive Factors
14.3 Variants of MF
14.4 Folliculotropic MF
14.4.1 Clinical Features
14.4.2 Histopathology
14.4.3 Treatment and Prognosis
14.5 Pagetoid Reticulosis (Woringer–Kolopp Disease)
14.6 Granulomatous Slack Skin
14.7 Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorders
14.8 Lymphomatoid Papulosis
14.8.1 Clinical Features
14.8.2 Histopathology
14.8.3 Treatment and Prognosis
14.9 Primary Cutaneous Anaplastic Large Cell Lymphoma
14.9.1 Clinical Features
14.9.2 Histopathology
14.9.3 Treatment and Prognosis
14.10 Subcutaneous Panniculitis-Like T-Cell Lymphoma
14.10.1 Clinical Features
14.10.2 Histopathology
14.10.3 Treatment and Prognosis
14.11 Primary Cutaneous Acral CD8+ T-Cell Lymphoma
14.11.1 Clinical Features
14.11.2 Histopathology
14.11.3 Treatment and Prognosis
14.12 Primary Cutaneous CD4-Positive Small/Medium T-Cell Lymphoproliferative Disorder
14.12.1 Clinical Features
14.12.2 Histopathology
14.12.3 Treatment and Prognosis
14.13 Conclusion
References
15: Large Granular Lymphocyte Leukemia
15.1 Introduction
15.1 LGL Leukemia: Clinical Aspects
15.1.1 Leukemic LGL Cytology and Immunophenotype
15.1.2 Diagnosis
15.1.3 Clinical Features
15.1.4 The Predicting Value of the Immunophenotype
15.1.5 Therapy
15.2 LGL Leukemia: Molecular Aspects
15.2.1 Pathogenesis
15.2.2 The Inciting Event
15.2.3 Bone Marrow Involvement
15.2.4 Peripheral Blood Inflammatory Cytokines
15.2.5 Clonal Drift
15.2.6 AICD Failure
15.2.7 JAK/STAT Pathway
15.2.8 Other Cell Survival Dysregulated Pathways
15.2.9 Neutropenia Molecular Mechanism
15.3 Concluding Remarks
References