Treatment of Leukemia and Lymphoma
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Table of contents
- Copyright Pageiv
- Contentsv
- Contributorsxi
- Prefacexv
- Chapter 1. Kinase Inhibitors in Leukemia1
- I. Chapter Overview1
- II. Introduction2
- III. Factors in Identifying an Ideal Therapeutic Target2
- IV. Kinase Targets in Leukemia: Current Treatment Options5
- V. Kinase Targets in Leukemia: On the Horizon14
- VI. Conclusions20
- References20
- Chapter 2. Therapy of Acute Promyelocytic Leukemia35
- I. Chapter Overview35
- II. Introduction35
- III. Disease Background and Biology36
- IV. Treatment Approaches38
- References52
- Chapter 3. Investigational Agents in Myeloid Disorders59
- I. Chapter Overview59
- II. Introduction60
- III. Nucleoside Analogs60
- IV. Reversal of Multidrug Resistance66
- V. Biological Agents68
- VI. Signaling Modulators74
- VII. Conclusions82
- References82
- Chapter 4. Methodologic Issues in Investigation of Targeted Therapies in Acute Myeloid Leukemia99
- I. Chapter Overview99
- II. Introduction99
- III. Patient Selection for Targeted Therapy Trials in Acute Myeloid Leukemia100
- IV. Endpoints for Clinical Trials of TTs in ANL102
- V. Need for Randomized Trials of TTs and a Proposed Statistical Design103
- References106
- Chapter 5. Purine Analogs in Leukemia107
- I. Chapter Overview107
- II. Introduction107
- III. Mechanisms of Action108
- IV. Purine Analogs in Chronic Lymphocytic Leukemia110
- V. Purine Analogs in Hairy Cell Leukemia114
- VI. Purine Analogs in Acute Myeloid Leukemia114
- VII. Purine Analogs in Chronic Myeloid Leukemia116
- VIII. Purine Analogs in Allogeneic Stem Cell Transplantation117
- IX. Conclusion and Future Directions118
- References118
- Chapter 6. Monoclonal Antibody Therapy in Lymphoid Leukemias127
- I. Chapter Overview127
- II. Introduction128
- III. Chronic Lymphocytic Leukemia130
- IV. T-Cell Prolymphocytic Leukemia152
- V. Hairy Cell Leukemia153
- VI. Conclusions155
- References156
- Chapter 7. Native Antibody and Antibody-Targeted Chemotherapy for Acute Myeloid Leukemia169
- I. Chapter Overview169
- II. Introduction170
- III. Lingering Questions Regarding Immunoconjugate Therapies178
- IV. Summary180
- References181
- Chapter 8. Radioimmunotherapy of Leukemia185
- I. Chapter Overview185
- II. Introduction186
- III. Antigenic Targets186
- IV. Radioisotope Selection187
- V. Radiolabeling190
- VI. Pharmacokinetics and Dosimetry193
- VII. Radioimmunotherapy with b-Particle Emitters194
- VIII. Radioimmunotherapy with a-Particle Emitters199
- IX. Summary202
- References203
- Chapter 9. Immunotoxins and Toxin Constructs in the Treatment of Leukemia and Lymphoma209
- I. Chapter Overview209
- II. Introduction209
- III.‘‘Targets of Opportunity’’ in Leukemia and Lymphoma210
- References221
- Chapter 10. Antibody Therapy of Lymphoma229
- I. Chapter Overview229
- II. History230
- III. Chimeric Anti-CD20„A Clinical Breakthrough232
- IV. Alternative Molecular Targets234
- V. Mechanisms of Action236
- VI. Radioimmunotherapy241
- VII. mAbs Combined with Chemotherapy243
- VIII. mAbs Combined with Immunotherapy246
- IX. Conclusion247
- References248
- Chapter 11. Vaccines in Leukemia255
- I. Chapter Overview255
- II. Introduction256
- III. Potential Target Antigens257
- IV. Clinical Vaccine Trials with Leukemia-Associated Antigens262
- V. Conclusion264
- References264
- Chapter 12. Therapeutic Idiotype Vaccines for Non-Hodgkin’s Lymphoma271
- I. Chapter Overview271
- II. Introduction272
- III. Development of the Idiotype Vaccine Approach272
- IV. Recombinant Idiotype Vaccines278
- V. Phase III Idiotype Vaccine Trials282
- VI. Pharmacologic Considerations and Integration with Standard Therapies283
- VII. New and Ongoing Phase I/II Clinical Trials of Idiotype Vaccination285
- VIII. Conclusions and Future Prospects287
- References288
- Chapter 13. Cytokine Modulation of the Innate Immune System in the Treatment of Leukemia and Lymphom295
- I. Chapter Overview295
- II. Introduction296
- III. Effector Cells of the Innate Immune System: Relevance to Cytokine Therapy296
- IV. Cytokine Therapy: Exploiting Innate Immune Effectors302
- V. Novel Approaches for the Immunomodulation of Leukemia and Lymphoma306
- VI. Conclusion311
- References311
- Chapter 14. Donor Lymphocyte Infusions319
- I. Chapter Overview319
- II. Introduction319
- III. Graft-Versus-Leukemia: Experimental Models320
- IV. Donor Lymphocyte Infusions for Chronic Myeloid Leukemia321
- V. Multiple Myeloma324
- VI. Myelodysplastic Syndrome and Acute Leukemia326
- VII. Chronic Lymphocytic Leukemia and Lymphoma327
- VIII. EBV-Associated Lymphoproliferative Disorders After Bone Marrow Transplantation327
- IX. Complications of DLI328
- X. Methods to Enhance the GVL Response after DLI330
- XI. Mediators of the GVL Effect330
- XII. Potential Targets of the GVL Effect332
- XIII. Tumor-Specific Targets of the DLI/GVL Response335
- XIV. Future Directions336
- References337
- Chapter 15. Somatic Cell Engineering and the Immunotherapy of Leukemias and Lymphomas347
- I. Chapter Overview347
- II. Introduction348
- III. Immune Effector Cell Activation350
- IV. Immunization Against Hematologic Malignancies: Tumor Cell Vaccines351
- V. Immunization Against Hematologic Malignancies: Dendritic Cell Vaccines357
- VI. Adoptive T-Cell Therapy Directed Against Hematologic Malignancies359
- VII. Conclusion362
- References363
- Index371
- Contents of Previous Volumes383
- Color Plate SectionPlate1
New Treatments of Leukemia and Lymphoma describes the most important advances in the therapy of hematopoietic cancers that have been derived from recent discoveries in cancer cell biology, kinase biochemistry, and immunology.
Detailed descriptions of the large number of new and effective agents that have recently become available for the treatment of leukemias and lymphomas as well as an understanding of their mechanisms of action and their integration into current therapy are provided. A number of experimental drug reagents currently in clinical investigation are also discussed. The therapies include conventional anti-metabolites, monoclonal antibodies directed to cell surface receptors, antibodies tagged with toxins and radiopharmaceuticals, inhibitors of specific kinases, stem cell transplants, and engineered T-cells designed to selectively target hematopoietic cancers.
The contents of the book will allow practitioners and investigators alike to understand what is current and state of the art as well as what to look for in the future.
* Provides an up-to-date, state of the art discussion of a rapidly changing field
* Great breadth covering conventional chemotherapeutic agents, biologic agents such as antibodies, novel small molecule inhibitors and genetically engineered cells
* Written by international experts in each of the fields
Detailed descriptions of the large number of new and effective agents that have recently become available for the treatment of leukemias and lymphomas as well as an understanding of their mechanisms of action and their integration into current therapy are provided. A number of experimental drug reagents currently in clinical investigation are also discussed. The therapies include conventional anti-metabolites, monoclonal antibodies directed to cell surface receptors, antibodies tagged with toxins and radiopharmaceuticals, inhibitors of specific kinases, stem cell transplants, and engineered T-cells designed to selectively target hematopoietic cancers.
The contents of the book will allow practitioners and investigators alike to understand what is current and state of the art as well as what to look for in the future.
* Provides an up-to-date, state of the art discussion of a rapidly changing field
* Great breadth covering conventional chemotherapeutic agents, biologic agents such as antibodies, novel small molecule inhibitors and genetically engineered cells
* Written by international experts in each of the fields