Moehler / Goldschmidt Multiple Myeloma

1. Auflage 2011
ISBN: 978-3-540-85772-3
Verlag: Springer Berlin Heidelberg
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 340 Seiten

Reihe: Medicine (R0)

Multiple myeloma is currently still an incurable disease, but during the past decade knowledge of its molecular pathogenesis has increased rapidly. This has led to remarkable progress in both diagnosis and therapy, including in particular the approval of novel and first-in-class drugs such as thalidomide, bortezomib, and lenalidomide. This book, written by internationally acknowledged experts, covers a wide range of topics relating to multiple myeloma, including history, epidemiology, pathophysiology, clinical features, staging, and prognostic systems. The principal focus, however, is on therapy, with detailed information on the various promising treatment options which give hope that this cancer will be transformed into a chronic disease or even become curable. Individualized therapy and the variety of supportive treatment options, as described in this volume, will help in achieving this goal, as well as in reducing adverse events and improving quality of life.

Autoren/Hrsg.

Moehler, Thomas

Goldschmidt, Hartmut

Inhaltsverzeichnis

1;Copyright Page;5
2;Dedication;6
3;Foreword;8
4;Preface;10
5;Acknowledgements;12
6;Contents;14
7;Contributors;22
8;Part I History and Epidemiology;25
8.1;1: History of Multiple Myeloma;26
8.1.1;1.1 Ancient Origins;27
8.1.1.1;1.1.1 Early Well-Documented Cases;27
8.1.2;1.2 Henry Bence Jones (1813–1873);30
8.1.3;1.3 Other Contributions to Bence Jones Proteinuria;33
8.1.4;1.4 Other Early Cases of Multiple Myeloma;34
8.1.4.1;1.4.1 The Case of Dr. Loos;34
8.1.4.2;1.4.2 The First Myeloma Case in America;35
8.1.4.3;1.4.3 Recognition of the Poor Prognosis Associated with Bence Jones Protein;36
8.1.4.4;1.4.4 Case Series;36
8.1.4.5;1.4.5 Plasma Cells;36
8.1.4.6;1.4.6 Antibodies;37
8.1.4.7;1.4.7 Electrophoresis;37
8.1.4.8;1.4.8 Monoclonal Versus Polyclonal Gammopathies;38
8.1.5;1.5 Alkylator and Corticosteroid-Based Therapy;38
8.1.5.1;1.5.1 Urethane;38
8.1.5.2;1.5.2 Melphalan;39
8.1.5.3;1.5.3 Prednisone;39
8.1.5.4;1.5.4 Alkylator Combinations;39
8.1.6;1.6 Stem Cell Transplantation;40
8.1.6.1;1.6.1 Novel Agents;40
8.1.6.1.1;1.6.1.1 Thalidomide;40
8.1.6.1.2;1.6.1.2 Bortezomib;41
8.1.6.1.3;1.6.1.3 Lenalidomide;42
8.1.7;References;42
8.2;2: Epidemiology of Multiple Myeloma;47
8.2.1;2.1 Descriptive Epidemiology;48
8.2.2;2.2 Etiology;48
8.2.2.1;2.2.1 Tobacco;48
8.2.2.2;2.2.2 Alcohol;51
8.2.2.3;2.2.3 Diet;51
8.2.2.4;2.2.4 Obesity;51
8.2.2.5;2.2.5 Physical Activity;52
8.2.2.6;2.2.6 Hormonal Factors;52
8.2.2.7;2.2.7 Environment and Occupation;52
8.2.2.8;2.2.8 Ionizing Radiation;52
8.2.2.9;2.2.9 Inheritance;53
8.2.2.10;2.2.10 Medical History, Viruses, Immunological Conditions;53
8.2.3;2.3 Summary;53
8.2.4;References;55
9;Part II Pathophysiology;58
9.1;3: Molecular Pathogenesis of Multiple Myeloma: Chromosomal Aberrations, Changes in Gene Expression, Cytokine Networks, and th;59
9.1.1;3.1 Survival, Growth, and Inhibitory Factors of Normal Plasma Cells;60
9.1.1.1;3.1.1 Survival and Growth Factors of Normal Plasma Cells and Their Generation;60
9.1.1.2;3.1.2 Inhibitory Factors Expressed by Normal Plasma Cells;63
9.1.2;3.2 Chromosomal Aberrations;64
9.1.2.1;3.2.1 Background and Methods;64
9.1.2.2;3.2.2 Types of Chromosomal Aberrations;66
9.1.2.3;3.2.3 Association of Chromosomal Aberrations;67
9.1.2.4;3.2.4 Clonal, Subclonal, and Progression-Related Aberrations and Chromosomal Instability;67
9.1.2.5;3.2.5 Prognostic Relevance of Chromosomal Aberrations;68
9.1.3;3.3 Changes in Gene Expression in Multiple Myeloma;70
9.1.3.1;3.3.1 Gene Expression–Based Classifications in Myeloma;70
9.1.3.2;3.3.2 Gene Expression and Risk Stratification;71
9.1.4;3.4 Proliferation and Cell Cycle Regulation;72
9.1.4.1;3.4.1 “Potential to Proliferate” of Normal Plasma Cells;72
9.1.4.2;3.4.2 D-Type Cyclin Expression in Myeloma;73
9.1.4.3;3.4.3 Proliferation of Malignant Plasma Cells;73
9.1.5;3.5 Myeloma Cell Survival and Proliferation Factors;74
9.1.5.1;3.5.1 Interferon Alpha/Interleukin-6 Family and Activation of the JAK/STAT and MAP Kinase Pathways;75
9.1.5.2;3.5.2 Factors Activating the PI-3 and MAP Kinase Pathways: Insulin-Like Growth Factor 1, Heparin-Binding Growth Factors;76
9.1.5.2.1;3.5.2.1 Insulin-Like Growth Factor 1 (IGF-1);76
9.1.5.2.2;3.5.2.2 Insulin;77
9.1.5.3;3.5.3 Heparin-Binding Factors;78
9.1.5.3.1;3.5.3.1 Heparin-Binding Epidermal Growth Factors;78
9.1.5.3.2;3.5.3.2 Hepatocyte Growth Factor (HGF);78
9.1.5.3.3;3.5.3.3 Fibroblast Growth Factor (FGF);79
9.1.5.4;3.5.4 Factors Activating NF-Kappa B: BAFF Family;79
9.1.5.5;3.5.5 Hierarchy of Myeloma Cell Growth Factors and Potential Clinical Applications;79
9.1.6;3.6 Multiple Myeloma Cells and the Microenvironment;80
9.1.6.1;3.6.1 Pathogenesis of Myeloma-Induced Bone Disease;81
9.1.6.2;3.6.2 Patterns and Healing of Bone Defects;83
9.1.6.3;3.6.3 Therapeutic Strategies for Treatment and Prevention of Myeloma Bone Disease;84
9.1.7;3.7 Pathogenetic Model of Multiple Myeloma;84
9.1.7.1;3.7.1 Disease Activity, Tumor Load, and Molecular Characteristics of Myeloma Cells;87
9.1.7.1.1;3.7.1.1 Describing Disease Activity;87
9.1.7.1.2;3.7.1.2 Interpatient Heterogeneity: Many and Multiple Myelomas;88
9.1.7.2;3.7.2 Multistep Transformation of Myeloma Cell Model;89
9.1.7.3;3.7.3 Transformation of Bone Marrow Microenvironment Model;90
9.1.7.3.1;3.7.3.1 Features of Normal Plasma Cells as Explanation for Those of Myeloma Cells;90
9.1.7.3.2;3.7.3.2 Pre-MGUS-Stage;90
9.1.7.3.3;3.7.3.3 MGUS-Stage/Smoldering Myeloma;90
9.1.7.3.4;3.7.3.4 Symptomatic Myeloma;91
9.1.8;References;92
9.2;4: Angiogenesis and Vasculogenesis in Multiple Myeloma: Role of Inflammatory Cells;107
9.2.1;4.1 Introduction;107
9.2.2;4.2 Angiogenesis and Antiangiogenesis in Multiple Myeloma;108
9.2.3;4.3 The Role of Inflammatory Cells in Tumor Angiogenesis;109
9.2.4;4.4 The Involvement of Macrophages in Vascular Mimicry in MM;110
9.2.5;4.5 The Involvement of Mast Cells in Vascular Mimicry in MM;111
9.2.6;4.6 Vasculogenesis by Hematopoietic Stem and Progenitor Cells;112
9.2.7;4.7 Concluding Remarks;113
9.2.8;References;113
9.3;5: Immunology and Immunotherapeutic Approaches in Multiple Myeloma;116
9.3.1;5.1 Introduction;116
9.3.2;5.2 Myeloma-Associated Antigens;117
9.3.3;5.3 Vaccination;118
9.3.4;5.4 Immune Evasion;120
9.3.5;5.5 Regulatory T Cells;121
9.3.6;5.6 Humoral Immunotherapy;121
9.3.7;5.7 Adoptive Cellular Therapy;122
9.3.8;5.8 Conclusion;123
9.3.9;References;123
10;Part III Clinical Features;129
10.1;6: Monoclonal Gammopathy and Smoldering Multiple Myeloma: Diagnosis, Staging, Prognosis, Management;130
10.1.1;6.1 Definition of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (sMM);131
10.1.2;6.2 Prevalence of MGUS;131
10.1.3;6.3 Differential Diagnosis and Diagnostic Assessment;133
10.1.3.1;6.3.1 Initial Diagnostic Assessment;133
10.1.3.2;6.3.2 Follow-up Recommendations;134
10.1.4;6.4 Risk Factors for Progression;135
10.1.4.1;6.4.1 Prognostic Factors for Progression for Patients with MGUS;135
10.1.4.2;6.4.2 Prognostic Factors for Progression of sMM;136
10.1.4.2.1;6.4.2.1 Immunophenotyping and Immunoparesis;138
10.1.4.2.2;6.4.2.2 Role of Imaging in Prognostic Evaluation of sMM;138
10.1.4.3;6.4.3 Genetic Risk Stratification;139
10.1.5;6.5 Etiology and Pathogenesis of MGUS and sMM and Considerations Regarding Primary Prevention;139
10.1.5.1;6.5.1 Population-Based Studies;139
10.1.5.2;6.5.2 Concept of Chronic Antigenic Stimulation;139
10.1.5.3;6.5.3 Molecular Genetics and Cytogenetics;140
10.1.5.4;6.5.4 Concepts for Secondary Prevention of Progression to Multiple Myeloma and Other Lymphoproliferative Diseases;141
10.1.5.5;6.5.5 Summary of Clinical Studies to Halt Progression;141
10.1.5.5.1;6.5.5.1 Bisphosphonates;142
10.1.5.5.2;6.5.5.2 Alkylating Agents and Corticosteroids;142
10.1.5.5.3;6.5.5.3 Thalidomide;142
10.1.5.5.4;6.5.5.4 Immunotherapy and Interference with Cytokine Network;143
10.1.5.5.5;6.5.5.5 Summary and Brief Outlook Regarding Clinical Studies;143
10.1.6;6.6 Summary and Conclusions;143
10.1.7;References;144
10.2;7: Imaging in Multiple Myeloma;149
10.2.1;7.1 Introduction;149
10.2.2;7.2 Imaging Methods;150
10.2.2.1;7.2.1 Morphologic Imaging;150
10.2.2.2;7.2.2 Functional Imaging;151
10.2.2.2.1;7.2.2.1 Dynamic Contrast-Enhanced MRI (DCE MRI);151
10.2.2.2.2;7.2.2.2 Diffusion-Weighted Imaging (DWI);151
10.2.2.2.3;7.2.2.3 Bone Scintigraphy and Positron Emission Tomography (PET);152
10.2.3;7.3 Radiological–Pathological Correlation;152
10.2.4;7.4 Differential Diagnosis;158
10.2.5;7.5 Staging;159
10.2.6;7.6 Treatment Effects;160
10.2.7;7.7 Prognostic Factors;160
10.2.8;7.8 The Radiologist’s Tasks;161
10.2.9;References;161
11;Part IV Therapy;164
11.1;8: Novel Drugs in Myeloma: Harnessing Tumour Biology to Treat Myeloma;165
11.1.1;8.1 Introduction;165
11.1.2;8.2 Intracellular Drug Targets;166
11.1.2.1;8.2.1 Targeting Signalling Pathways Within Myeloma Cells;166
11.1.2.1.1;8.2.1.1 The Ras/Raf/MEK/MAPK Pathway;167
11.1.2.1.2;8.2.1.2 The Janus Kinase (JAK)/STAT Pathway;168
11.1.2.1.3;8.2.1.3 The Phosphatidylinositol-3 Kinase (PI3-K)/Akt Pathway;169
11.1.2.1.4;8.2.1.4 The Nuclear Factor-Kappa B (NF-kB) Pathway and the Ubiquitin Proteasome System;170
11.1.2.1.5;8.2.1.5 The Wingless/int (Wnt)/b-Catenin Pathway;172
11.1.2.2;8.2.2 Targeting the Unfolded Protein Response;172
11.1.2.3;8.2.3 Targeting Chromatin;173
11.1.2.3.1;8.2.3.1 Histone Deacetylase (HDAC) Inhibitors;174
11.1.2.3.2;8.2.3.2 Hypomethylating Agents;175
11.1.2.3.3;8.2.3.3 New Alkylators;175
11.1.2.4;8.2.4 Targeting Intracellular Cell Cycle Regulatory Proteins;176
11.1.2.4.1;8.2.4.1 Cyclin D Kinases;176
11.1.2.4.2;8.2.4.2 Aurora Kinases;176
11.1.2.4.3;8.2.4.3 Pim Kinases;177
11.1.2.4.4;8.2.4.4 Inhibitor of Apoptosis Proteins;177
11.1.3;8.3 Extracellular Drug Targets;177
11.1.3.1;8.3.1 Targeting Cytokines or Their Receptors;177
11.1.3.1.1;8.3.1.1 Interleukin-6 (IL-6);178
11.1.3.1.2;8.3.1.2 Insulin-Like Growth Factor-1 (IGF-1);178
11.1.3.1.3;8.3.1.3 Fibroblast Growth Factor (FGFR3);179
11.1.3.1.4;8.3.1.4 Vascular Endothelial Growth Factor (VEGF);179
11.1.3.1.5;8.3.1.5 Platelet Derived Growth Factor Receptor b (PDGFRb);179
11.1.3.1.6;8.3.1.6 CD40 Ligand;180
11.1.3.1.7;8.3.1.7 B-Cell Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL);180
11.1.3.1.8;8.3.1.8 TNF-Related Apoptosis-Inducing Ligand (TRAIL);180
11.1.3.1.9;8.3.1.9 Fas;180
11.1.3.1.10;8.3.1.10 p38 mitogen-activated protein kinase (MAPK);180
11.1.3.2;8.3.2 Targeting Myeloma Cell Adhesion Molecules;181
11.1.3.2.1;8.3.2.1 Stromal Cell Derived Factor-1 (SDF-1);181
11.1.3.2.2;8.3.2.2 Cell Surface 1 Surface Antigen (CS1);181
11.1.3.2.3;8.3.2.3 CD56;182
11.1.3.2.4;8.3.2.4 CD38;182
11.1.3.2.5;8.3.2.5 CD138;182
11.1.3.2.6;8.3.2.6 CD66;182
11.1.3.3;8.3.3 Targeting the Host Immune System;183
11.1.3.3.1;8.3.3.1 Immunomodulatory Drugs (IMiDs);183
11.1.3.3.1.1;Thalidomide;183
11.1.3.3.1.2;Lenalidomide (CC-5013);184
11.1.3.3.1.3;Pomalidomide (CC4047);185
11.1.3.4;8.3.4 Targeting Bone Disease;185
11.1.3.4.1;8.3.4.1 Receptor Activator of NF-kB Ligand (RANKL);186
11.1.3.4.2;8.3.4.2 Dickkopf-1 (DKK1) and Wingless/int (Wnt);186
11.1.3.4.3;8.3.4.3 Macrophage Inflammatory Protein 1-a (MIP-1a);186
11.1.3.4.4;8.3.4.4 Activin A;187
11.1.4;8.4 Conclusion;187
11.1.5;References;188
11.2;9: Firstline Treatment and Maintenance in Newly Diagnosed Multiple Myeloma Patients;202
11.2.1;9.1Frontline Treatment in MM Patients Eligible for High-Dose Therapy;203
11.2.1.1;9.1.1Induction Treatment: What Combination of New Drugs?;203
11.2.1.1.1;9.1.1.1Two-Drug Induction Regimens;204
11.2.1.1.1.1;Thalidomide-Based Induction Regimens;204
11.2.1.1.1.2;Bortezomib-Based Induction Regimens;204
11.2.1.1.1.3;Lenalidomide-Based Induction Regimens;204
11.2.1.1.2;9.1.1.2Three-Drug Regimens;204
11.2.1.1.2.1;Anthracyclins or Cyclophosphamide in Combination with Thalidomide, Bortezomib, or Lenalidomide;205
11.2.1.1.2.2;Bortezomib in Combination with Thalidomide or Lenalidomide;205
11.2.1.1.3;9.1.1.3Four-Drug Induction Regimens;206
11.2.1.2;9.1.2Autologous Stem Cell Transplantation Upfront or at the Time of Relapse?;207
11.2.1.3;9.1.3Maintenance/Consolidation Treatment;208
11.2.2;9.2Frontline Treatment in Elderly MM Patients;209
11.2.2.1;9.2.1What Is the Best Combination with Alkylating Agents?;210
11.2.2.1.1;9.2.1.1Thalidomide;210
11.2.2.1.2;9.2.1.2Bortezomib;211
11.2.2.1.3;9.2.1.3Lenalidomide;212
11.2.2.1.4;9.2.1.4Combinations of New Agents Plus MP;212
11.2.2.1.4.1;VMPT;212
11.2.2.2;9.2.2Firstline Treatment: Can New Agents Replace Alkylators?;213
11.2.2.2.1;9.2.2.1Thalidomide;213
11.2.2.2.2;9.2.2.2Lenalidomide;213
11.2.2.2.3;9.2.2.3Combinations of New Agents;214
11.2.2.2.3.1;Bortezomib and Thalidomide;214
11.2.2.3;9.2.3Can We Reduce Toxicities of New Drugs-Incorporating Regimens?;214
11.2.2.3.1;9.2.3.1Bortezomib in a Weekly Schedule;214
11.2.2.3.2;9.2.3.2Low-Dose Dexamethasone;214
11.2.2.3.3;9.2.3.3Prevention of IMiDs-Associated Venous Thromboembolism (VTE);215
11.2.2.4;9.2.4Maintenance Therapy in Elderly;215
11.2.3;References;216
11.3;10: High-Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma;220
11.3.1;10.1Introduction;221
11.3.2;10.2Peripheral Blood Stem Cell Mobilization;221
11.3.2.1;10.2.1The Role of Adhesion Molecules;221
11.3.2.2;10.2.2The Role of Hematopoietic Growth Factors;223
11.3.2.3;10.2.3The Role of Cytotoxic Stem Cell Mobilization;225
11.3.2.4;10.2.4The Role of Pegfilgrastim for Stem Cell Mobilization;226
11.3.3;10.3High-Dose Therapy and Autologous Stem Cell Transplantation;228
11.3.3.1;10.3.1The Beginning of High-Dose Therapy in the 1980;228
11.3.3.2;10.3.2The Role of Purging of the Autograft;229
11.3.3.3;10.3.3The Role of the Conditioning Regimen;230
11.3.3.4;10.3.4Supportive Care During High-Dose Chemotherapy;231
11.3.3.5;10.3.5High-Dose Chemotherapy Is Superior to Conventional Chemotherapy;232
11.3.3.6;10.3.6Timing of High-Dose Chemotherapy;234
11.3.3.7;10.3.7Tandem Autologous Transplantation;234
11.3.3.8;10.3.8The Role of Induction Treatment;235
11.3.3.9;10.3.9The Role of Consolidation or Maintenance Treatment;236
11.3.3.10;10.3.10Prognostic Factors;237
11.3.3.11;10.3.11Targeted Versus High-Dose Chemotherapy;239
11.3.4;References;240
11.4;11: Therapy of Relapsed and Refractory Multiple Myeloma;252
11.4.1;11.1Introduction;253
11.4.2;11.2Diagnostic Workup of Patients at Relapse;253
11.4.3;11.3Conventional Treatment of Relapsed/Refractory Disease;253
11.4.4;11.4High-Dose Chemotherapy (HDCT) Supported by Autologous Stem Cell Transplantation;254
11.4.5;11.5Allogeneic Stem Cell Transplantation;255
11.4.6;11.6Thalidomide and Immunomodulatory Drugs;258
11.4.6.1;11.6.1Thalidomide as Single Agent and Combined with Corticosteroids;258
11.4.6.2;11.6.2Thalidomide in Combination with Chemotherapy/Corticosteroids;259
11.4.6.3;11.6.3Lenalidomide;262
11.4.6.4;11.6.4Lenalidomide Combination Therapies;262
11.4.6.5;11.6.5Pomalidomide;264
11.4.7;11.7Bortezomib;264
11.4.7.1;11.7.1Bortezomib Single Agent;264
11.4.7.2;11.7.2Bortezomib Combination Therapy;265
11.4.8;11.8Novel Proteasome Inhibitors;267
11.4.9;11.9Combination of Novel Agents;268
11.4.10;11.10Emerging Therapies and Novel Pathways;273
11.4.11;11.11Prognostic Factors;273
11.4.12;11.12Therapeutic Strategy for Relapsed/Refractory Myeloma Patients;273
11.4.13;References;276
11.5;12: Allogeneic Transplantation in Multiple Myeloma;285
11.5.1;12.1 Introduction;286
11.5.2;12.2 Myeloablative High Dose Conditioning;286
11.5.3;12.3 Molecular Remission;287
11.5.4;12.4 Source of Stem Cells;287
11.5.5;12.5 Reduced Intensity conditioning (RIC);288
11.5.5.1;12.5.1 Retrospective Studies;288
11.5.5.2;12.5.2 Prospective Studies;288
11.5.6;12.6 How to Improve Results of Allogeneic Transplantation?;291
11.5.6.1;12.6.1 Donor Lymphocyte Transfusions;291
11.5.6.2;12.6.2 NK Cells Have Antimyeloma Effect and Moderate GVHD;292
11.5.6.3;12.6.3 Role of Immunosuppressive Agents in the Conditioning Therapy;292
11.5.6.4;12.6.4 Targeted Drugs Pretransplant or Posttransplant;293
11.5.7;12.7 Conclusions;293
11.5.8;References;293
11.6;13: Radiotherapy;297
11.6.1;13.1 Solitary Plasmocytoma;297
11.6.1.1;13.1.1 Diagnostic Workup;298
11.6.1.2;13.1.2 Radiotherapy of SBP;298
11.6.1.3;13.1.3 Radiotherapy of EP;299
11.6.1.4;13.1.4 Treatment Toxicity;299
11.6.2;13.2 Palliative Treatment of Multiple Myeloma;299
11.6.2.1;13.2.1 Pain Control;300
11.6.2.2;13.2.2 Recalcification;300
11.6.3;13.3 Total Body Irradiation (TBI);301
11.6.4;References;302
11.7;14: Osteoplastic Procedures for the Treatment of Vertebral Complications in Multiple Myeloma Patients;304
11.7.1;14.1 Introduction;305
11.7.2;14.2 Osteoplastic Procedures;305
11.7.3;14.3 Balloon Kyphoplasty;305
11.7.4;14.4 Vertebroplasty;306
11.7.5;14.5 Comparison of Kyphoplasty and Vertebroplasty;307
11.7.6;14.6 Indications and Contraindications;307
11.7.7;14.7 Randomized Controlled Studies of Osteoplastic Procedures for Vertebral Osteoporotic Fractures;308
11.7.8;14.8 Studies Using Kyphoplasty and Vertebroplasty in Patients with Multiple Myeloma;309
11.7.9;References;316
11.8;15: Supportive Therapy in Multiple Myeloma;318
11.8.1;15.1 Introduction;318
11.8.2;15.2 Myeloma Bone Disease;319
11.8.2.1;15.2.1 Mechanisms of Bone Disease;319
11.8.2.2;15.2.2 Bone Fractures;320
11.8.2.3;15.2.3 Vertebral Lesions;320
11.8.2.4;15.2.4 Bisphosphonates;320
11.8.2.4.1;15.2.4.1 Adverse Events of Bisphosphonates;322
11.8.2.4.1.1;Osteonecrosis of the Jaw (ONJ);322
11.8.2.4.2;15.2.4.2 Guidelines for the Use of Bisphosphonates;325
11.8.2.4.3;15.2.4.3 Prophylactic Measures for ONJ;325
11.8.3;15.3 Hypercalcemia;325
11.8.3.1;15.3.1 Diagnosis and Symptoms;325
11.8.3.2;15.3.2 Treatment of Hypercalcemia;326
11.8.3.2.1;15.3.2.1 Rehydration;326
11.8.3.2.2;15.3.2.2 Bisphosphonates;326
11.8.3.2.3;15.3.2.3 Calcitonin and Corticosteroids;327
11.8.4;15.4 Anemia;327
11.8.4.1;15.4.1 Pathogenesis of Anemia;327
11.8.4.2;15.4.2 Clinical Symptoms of Anemia;327
11.8.4.3;15.4.3 Treatment of Anemia;328
11.8.4.3.1;15.4.3.1 Transfusions;328
11.8.4.3.2;15.4.3.2 Erythropoiesis-Stimulating Proteins (ESAs);328
11.8.4.3.3;15.4.3.3 Treatment Recommendations for ESAs;330
11.8.5;15.5 Infections;331
11.8.5.1;15.5.1 Causes of Infections;331
11.8.5.2;15.5.2 Prophylaxis of Infections;332
11.8.5.3;15.5.3 Vaccination;333
11.8.5.4;15.5.4 Treatment of Infections;333
11.8.6;15.6 Pain;334
11.8.6.1;15.6.1 Characteristics and Causes of Pain;334
11.8.6.2;15.6.2 Medical Pain Treatment;335
11.8.7;15.7 Renal Failure;336
11.8.7.1;15.7.1 Prevalence and Causes of Renal Failure;336
11.8.7.2;15.7.2 Management of Myeloma-Induced Renal Failure;337
11.8.8;References;337
12;Appendix: Staging and Prognosis Systems;345