PEDIATRIC LYMPHOMAS

- Comprehensive textbook of Hodgkin's and non-Hodgkin's lymphomas.
- Includes clinical, pathologic and molecular biology of each subtype of lymphoma.
- The authors are leaders in the field of childhood lymphomas.
The book covers the epidemiology, pathology, molecular biology, clinical features, diagnosis, and treatment of Hodgkin and non-Hodgkin lymphomas in children and adolescents. It is a combined effort of investigators who are leaders in the field of childhood lymphomas.
Introductory chapters on Hodgkin and non-Hodgkin lymphomas in children provide a concise historical overview. All chapters have a stand-alone structure and those regarding the individual subtypes of lymphomas provide up-to-date results of recent clinical trials and practical guidelines for work-up and treatment.
The pathology chapters are comprehensive and include excellent photographs as well as detailed reviews of the scientific advances pertaining to the molecular pathogenesis of each type of malignant lymphoma seen in childhood. There is also a concise chapter on post-transplant lymphoproliferative disease and lymphomas associated with congenital and acquired immunodeficiency states.
The book is at the level of subspecialists in pediatric hematology and oncology, radiation oncology, pediatric surgery and hematopathology.

Contents
1 Introduction and Historical Background:
Pediatric Hodgkin Lymphoma
S.S. Donaldson
1.1 The Way It Was . 1
1.2 Lessons from the Children .3
1.3 The Hidden Secrets –The Discovery of Late Eff ects.3
1.4 Current Optimal Management. 4
References . 4
2 Biology and Pathology of Hodgkin’s Disease
R.E. Hutchinson and A. Uner
2.1 History of Hodgkin’s Disease Pathologic Classifi cation.7
2.2 Lineage of Hodgkin Reed-Sternberg cells; B-cell phenotype. 9
2.3 Some Evidence of Antigen-Presenting Function.10
2.4 Apoptosis .10
2.5 NF-kappaB.11
2.6 Jak/STAT Pathways.12
2.7 Tumor Necrosis Factor Receptor (TNFR) Family.12
2.8 Tumor Necrosis Factor Receptor-Associated Factors (TRAFs).12
2.9 Cytokines and Chemokines.13
2.10 Cytogenetics.14
2.11 Gene Profi le .14
2.12 Association with EBV.14
2.13 Pathology of Classical Hodgkin Lymphoma.16
2.14 Immunophenotype of Classical HRS cells.17
2.15 Flow Cytometry.18
2.16 Histologic Classifi cation of CHL.19
2.16.1 Nodular Sclerosis HL.19
2.16.2 Mixed Cellularity HL.20
2.16.3 Nodular Lymphocyte Rich CHL.21
2.16.4 Lymphocyte Depleted HL. 22
2.17 Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL).22
2.18 Hodgkin Lymphoma in the Setting of HIV Infection.23
2.19 Bone Marrow Involvement and Histologic Staging.23
2.20 Pathology of Relapse and Second Malignancy.24
2.21 Diff erential Diagnosis of HL.25
References.27
3 Treatment of Pediatric Hodgkin Lymphoma
M.M. Hudson, C. Schwartz, and L.S. Constine
3.0 Introduction.35
3.1 Clinical Presentation.36
3.1.1 Systemic Symptoms.37
3.1.2 Laboratory Evaluation.37
3.1.3 Immunologic Status.38
3.2 Diff erential Diagnosis.39
3.3 Diagnostic Evaluation and Staging.40
3.4 Prognostic Factors.43
3.5 Combination Chemotherapy.45
3.6 Chemotherapy Alone Versus Combined Modality Therapy.49
3.7 Risk-Adapted Therapy.51
3.7.1 Treatment of Low-Risk Disease.51
3.7.2 Treatment of Intermediate- and High-Risk Disease.53
3.8 Principles of Radiation Therapy.54
3.8.1 Volume Considerations.56
3.8.2 Dose Considerations . 58
3.8.3 Energy. 59
3.9 Summary Recommendations for Primary Disease/Selection of Therapy.59
3.10 Acute Eff ects of Therapy. 59
3.10.1 Chemotherapy Side-Eff ects.59
3.10.2 Radiation Side-Eff ects.61
3.11 Future Directions.61
References.61
4 Treatment of Relapsed/Refractory Hodgkin Lymphoma
T.M. Trippett and A. Chen
4.1 Introduction.67
4.2 Strategies for Re-induction.67
4.2.1 Role of Re-induction Chemotherapy. 68
4.2.2 Standard Re-induction with ICE.68
4.2.3 Re-induction with Ifosfamide/Vinorelbine (IV).69
4.3 High-Dose Therapy.70
4.3.1 Immunomodulation as a Therapeutic Strategy to Augment High-Dose Therapy. 71
4.3.2 Reduced-Intensity/Non-myeloablative Allogeneic Stem cell Transplantation. 72
4.4 Salvage Strategies Following Transplantation. 72
4.4.1 Combination Chemotherapy with Gemcitabine/Vinorelbine (GEM/VRB).73
4.4.2 Molecular Targeting of the NF-?B Pathway.74
4.4.2.1 Activation of NF-??.74
4.4.2.2 Inhibition of NF-?B Through Proteasome Inhibition.75
4.4.2.3 Adult Clinical Trials.76
4.4.2.4 Pediatric Clinical Trials.77
4.4.2.5 Novel Retrieval Strategies Incorporating Proteasome Inhibition with Bortezomib. 77
4.4.3 Targeted Immunotherapy Strategies. 77
4.4.3.1 Epstein-Barr VirusDirected Therapy.77
4.4.3.2 Monoclonal Antibodies Targeting Receptors Expressed in HL.78
4.4.3.3 Radiolabeled Immunoglobulin Therapy in HL. 79
4.5 Future Considerations.79
References . 79
5 Non-Hodgkin’s Lymphoma:Introduction and Historical Background
S.B. Murphy
5.1 Introduction.85
5.2 The Early Era, Pre-1970. 86
5.3 The Latter Era, Post-1970s. 86
References. 88
6 Biology and Pathology of Pediatric Non-Hodgkin Lymphoma
S.L. Perkins and S.W. Morris
6.1 Introduction.91
6.2 Non-Hodgkin Lymphoma.91
6.3 Pathologic Analysis.93
6.3.1 Morphology.93
6.3.2 Immunophenotypic Analysis.94
6.3.3 Molecular and Cytogenetic Analysis.95
6.3.4 WHO Classifi cation of Hematolymphoid Tumors.100
6.4 Molecular Pathogenesis of Pediatric NHL.101
6.5 Burkitt Lymphomas.101
6.5.1 Pathology.101
6.5.2 Biology and Molecular Mechanisms.104
6.6 Diff use Large B-Cell Lymphomas.107
6.6.1 Pathology.107
6.6.2 Biology and Molecular Mechanisms.109
6.7 Anaplastic Large-Cell Lymphoma.112
6.7.1 Pathology.112
6.7.2 Biology and Molecular Mechanisms.117
6.8 Lymphoblastic Lymphoma.119
6.8.1 Pathology.119
6.8.2 Biology and Molecular Mechanisms.121
References.127
7 B-Cell Lymphoma/Burkitt Lymphoma
I. Magrath
7.1 Introduction.142
7.2 Diagnosis and Imaging.142
7. 2.1 Burkitt Lymphoma.142
7.7.2 Diff use Large B-cell Lymphoma.143
7.2.3 Burkitt-like Lymphoma.144
7.2.4 HIV-Associated B-cell Lymphomas.144
7.2.5 Imaging Studies.144
7.3 Clinical Features.146
7.4 Staging.148
7.4.1 Staging Procedures.150
7.5 Treatment.151
7.5.1 Early Studies in Africa.151
7.5.2 Non-Cross-Resistant Drugs and Combination Therapy.152
7.5.3 Therapy Directed Towards CNS Disease.154
7.5.4 Early Studies in the USA .154
7.5.5 Comparison with Leukemia Treatment.155
7.5.6 Critical Components of Modern Treatment Protocols.155
7.5.6.1 Basic Drugs.155
7.5.6.2 High-Dose MTX.156
7.5.6.3 The Role of Additional Drugs.156
7.5.6.4 Dose Density.157
7.5.6.5 Risk Adaptation.157
7.5.6.6 Prevention of CNS Disease.159
7.5.6.7 Treatment of DLBCL with Diff erent Regimens.160
7.5.6.8 Role of Surgery.160
7.5.6.9 Role of Radiation.161
7.5.6.10 Tumor Lysis Syndrome.162
7.6 Prognostic Factors.163
7.6.1 Tumor Burden and Stage.163
7.6.2 Rapidity of Response.164
7.6.3 Age and Sex.164
7.6.4 Histology.164
7.6.5 Molecular Characteristics.165
7.7 Outcome.165
7.8 Management of Relapse.166
7.9 Follicle Center Cell and Marginal Zone Lymphomas.167
7.10 Future Prospects.167
References.168
8 Anaplastic Large-Cell Lymphoma
A. Reiter
8.1 Introduction.175
8.2 Diagnosis and Imaging.177
8.3 Clinical Features.178
8.4 Staging. 181
8.5 Treatment and Outcome.181
8.5.1 Stratifi cation of Treatment Intensity.185
8.5.2 CNS Prophylaxis and CNS Therapy.185
8.5.3 Role of Local Therapy Modalities and Pattern of Therapy Failure.186
8.6 Prognostic Factors.187
8.7 Management of Relapse.189
8.8 Future Prospects.190
References.192
9 Precursor B and Precursor T-Cell Lymphoblastic Lymphoma
J.T. Sandlund
9.1 Introduction.199
9.2 Diagnosis and Imaging.199
9.2.1 Diagnosis.199
9.2.2 Imaging/Staging.201
9.3 Clinical Features.202
9.4 Treatment.202
9.4.1 Initial Management.202
9.4.2 Treatment Overview.203
9.4.2.1 Limited Stage Disease. 203
9.4.2.2 Advanced Stage Disease. 204
9.4.2.3 Central Nervous System Prophylaxis and Treatment.205
9.5 Prognostic Factors.208
9.6 Outcome.208
9.7 Management of Relapse.208
9.8 Future Prospects.208
References.210
10 Cutaneous T-Cell Lymphomas and Rare T-Cell Non-Hodgkin Lymphomas
M.E. Kadin
10.1 Introduction.215
10.2 Mycosis Fungoides and Sezary Syndrome.216
10.2.1 Clinical Features.216
10.2.2 Pathology.217
10.2.3 Immunophenotype.218
10.2.4 Genetic Features.218
10.2.5 Prognosis. 219
10.2.6 Therapy . 220
10.3 CD30+ Cutaneous T-Cell Lymphomas Including Lymphomatoid Papulosis.221
10.4 Lymphomatoid Papulosis.221
10.4.1 Clinical Features. 221
10.4.2 Pathology.222
10.4.3 Immunophenotype.223
10.4.4 Genetic Features.223
10.4.5 Prognosis.223
10.5 Primary Cutaneous Anaplastic Large-cell Lymphoma.224
10.5.1 Clinical Features.224
10.5.2 Pathology.224
10.5.3 Diff erential Diagnosis.224
10.5.4 Immunophenotype.225
10.5.5 Genetic Features. 225
10.5.6 Therapy.225
10.6 Subcutaneous Panniculitis-like T-Cell Lymphoma.225
10.6.1 Clinical Features. 226
10.6.2 Pathology. 226
10.6.3 Immunophenotype. 226
10.6.4 Genetic Features.227
10.6.5 Therapy.227
10.7 Hepatosplenic T-Cell Lymphoma.227
10.7.1 Clinical Features. 227
10.7.2 Pathology. 227
10.7.3 Immunophenotype. 227
10.7.4 Genetic Features. 227
10.7.5 Therapy. 228
References. 228
11 Lymphoproliferative Disorders Related to Immunodefi ciencies
T.G. Gross and B. Shiramizu
11.1 Introduction.233
11.2 Epstein-Barr Virus.234
11.3 Post-transplant Lymphoproliferative Disease.236
11.3.1 PTLD Following Blood or Marrow Transplantation.239
11.3.2 PTLD Following Solid Organ Transplantation.240
11.4 HIV-Related Malignancies.242
11.5 Lymphoproliferative Disease in Primary Immunodefi ciencies.246
11.6 Summary.250
References.250
12 Late Eff ects Following Lymphoma Treatment
D.L. Friedman and A.T. Meadows
12.1 Introduction.259
12.2 Second Malignant Neoplasms.260
12.3 Neurocognitive.261
12.4 Cardiovascular.261
12.5 Pulmonary.263
12.6 Bone and Body Composition.264
12.7 Endocrine.264
12.7.1 Thyroid Gland.264
12.8 Reproductive Endocrine.265
12.8.1 Male Gonadal Function.265
12.8.2 Female Gonadal Function.265
12.8.3 Reproduction.266
12.9 Dental.267
12.10 Spleen.267
12.11 Psychosocial.268
12.12 Mortality.268
12.13 Monitoring for Late Eff ects.269
12.14 Research Challenges for Lymphoma Survivors.269
12.15 Future Directions.273
References .274
Subject Index.281