1;Preface;6<br />2;Contents;8<br />3;Contributors;12<br />4;Chapter 1 Introduction and Historical Background: Pediatric Hodgkin Lymphoma;14<br />4.1;1.1 The Way It Was;14<br />4.2;1.2 Lessons from the Children;16<br />4.3;1.3 The Hidden Secrets The Discovery of Late Eff ects;16<br />4.4;1.4 Current Optimal Management;17<br />4.5;References;17<br />5;Chapter 2 Biology and Pathology of Hodgkin s Disease;20<br />5.1;2.1 History of Hodgkin s Disease Pathologic Classification;20<br />5.2;2.2 Lineage of Hodgkin Reed-Sternberg cells; B-cell phenotype;22<br />5.3;2.3 Some Evidence of an Antigen-Presenting Function;23<br />5.4;2.4 Apoptosis;23<br />5.5;2.5 NF-kappaB;24<br />5.6;2.6 Jak/STAT Pathways;25<br />5.7;2.7 Tumor Necrosis Factor Receptor (TNFR) Family;25<br />5.8;2.8 Tumor Necrosis Factor Receptor-Associated Factors (TRAFs);25<br />5.9;2.9 Cytokines and Chemokines;26<br />5.10;2.10 Cytogenetics;27<br />5.11;2.11 Gene Profi le;27<br />5.12;2.12 Association with EBV;27<br />5.13;2.13 Pathology of Classical Hodgkin Lymphoma;29<br />5.14;2.14 Immunophenotype of Classical HRS Cells;30<br />5.15;2.15 Flow Cytometry;31<br />5.16;2.16 Histologic Classifi cation of CHL;32<br />5.16.1;2.16.1 Nodular Sclerosis HL;32<br />5.16.2;2.16.2 Mixed Cellularity HL;33<br />5.16.3;2.16.3 Nodular Lymphocyte Rich CHL;34<br />5.16.4;2.16.4 Lymphocyte Depleted HL;35<br />5.17;2.17 Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL);35<br />5.18;2.18 Hodgkin Lymphoma in the Setting of HIV Infection;36<br />5.19;2.19 Bone Marrow Involvement and Histologic Staging;36<br />5.20;2.20 Pathology of Relapse and Second Malignancy;37<br />5.21;2.21 Differential Diagnosis of HL;38<br />5.22;References;40<br />6;Chapter 3 Treatment of Pediatric Hodgkin Lymphoma;48<br />6.1;3.0 Introduction;48<br />6.2;3.1 Clinical Presentation;49<br />6.2.1;3.1.1 Systemic Symptoms;50<br />6.2.2;3.1.2 Laboratory Evaluation;50<br />6.2.3;3.1.3 Immunologic Status;51<br />6.3;3.2 Differential Diagnosis;52<br />6.4;3.3 Diagnostic Evaluation and Staging;53<br />6.5;3.4 Prognostic Factors;56<br />6.6;3.5 Combination Chemotherapy;58<br />6.7;3.6 Chemotherapy Alone Versus Combined Modality Therapy;62<br />6.8;3.7 Risk-Adapted Therapy;64<br />6.8.1;3.7.1 Treatment of Low-Risk Disease;64<br />6.8.2;3.7.2 Treatment of Intermediate- and High-Risk Disease;66<br />6.9;3.8 Principles of Radiation Therapy;67<br />6.9.1;3.8.1 Volume Considerations;69<br />6.9.2;3.8.2 Dose Considerations;71<br />6.9.3;3.8.3 Energy;72<br />6.10;3.9 Summary Recommendations for Primary Disease/Selection of Therapy;72<br />6.11;3.10 Acute Effects of Therapy;72<br />6.11.1;3.10.1 Chemotherapy Side-Effects;72<br />6.11.2;3.10.2 Radiation Side-Effects;74<br />6.12;3.11 Future Directions;74<br />6.13;References;74<br />7;Chapter 4 Treatment of Relapsed/Refractory Hodgkin Lymphoma;80<br />7.1;4.1 Introduction;80<br />7.2;4.2 Strategies for Re-induction;80<br />7.2.1;4.2.1 Role of Re-induction Chemotherapy;81<br />7.2.2;4.2.2 Standard Re-induction with ICE;81<br />7.2.3;4.2.3 Re-induction Therapy with Ifosfamide/Vinorelbine (IV);82<br />7.3;4.3 High-Dose Therapy;83<br />7.3.1;4.3.1 Immunomodulation as a Therapeutic Strategy to Augment High-Dose Therapy;84<br />7.3.2;4.3.2 Reduced-Intensity/Non-myeloablative Allogeneic Stem Cell Transplantation;85<br />7.4;4.4 Salvage Strategies Following Transplantation;85<br />7.4.1;4.4.1 Combination Chemotherapy with Gemcitabine/ Vinorelbine (GEM/VRB);86<br />7.4.2;4.4.2 Molecular Targeting of the NF-.B Pathway;87<br />7.4.3;4.4.3 Targeted Immunotherapy Strategies;90<br />7.5;4.5 Future Considerations;92<br />7.6;References;92<br />8;Chapter 5 Non-Hodgkin s Lymphoma Introduction and Historical Background;98<br />8.1;5.1 Introduction;98<br />8.2;5.2 The Early Era, Pre-1970;99<br />8.3;5.3 The Latter Era, Post-1970s;99<br />8.4;References;101<br />9;Chapter 6 Biology and Pathology of Pediatric Non-Hodgkin Lymphoma;104<br />9.1;6.1 Introduction;104<br />9.2;6.2 Non-Hodgkin Lymphoma;104<br />9.3;6.3 Pathologic Analysis;106<br />9.3.1;6.3.1 Morphology;106<br />9.3.2;6.3.2 Immunophenotypic Analysis;107<br />9.3.3;6.3.3 Molecular and Cytogenetic Analysis;108<br />9.3.4;6.3.4 WHO Classification of Hematolymphoid Tumors;113<br />9.4;6.4 Molecular Pathogenesis of Pediatric NHL;114<br />9.5;6.5 Burkitt Lymphomas;114<br />9.5.1;6.5.1 Pathology;114<br />9.5