Treatment of Leukemia and Lymphoma (eBook)

Cover 1
Copyright Page 5
Contents 6
Contributors 12
Preface 16
Chapter 1. Kinase Inhibitors in Leukemia 20
I. Chapter Overview 20
II. Introduction 21
III. Factors in Identifying an Ideal Therapeutic Target 21
IV. Kinase Targets in Leukemia: Current Treatment Options 24
V. Kinase Targets in Leukemia: On the Horizon 33
VI. Conclusions 39
References 39
Chapter 2. Therapy of Acute Promyelocytic Leukemia 54
I. Chapter Overview 54
II. Introduction 54
III. Disease Background and Biology 55
IV. Treatment Approaches 57
References 71
Chapter 3. Investigational Agents in Myeloid Disorders 78
I. Chapter Overview 78
II. Introduction 79
III. Nucleoside Analogs 79
IV. Reversal of Multidrug Resistance 85
V. Biological Agents 87
VI. Signaling Modulators 93
VII. Conclusions 101
References 101
Chapter 4. Methodologic Issues in Investigation of Targeted Therapies in Acute Myeloid Leukemia 118
I. Chapter Overview 118
II. Introduction 118
III. Patient Selection for Targeted Therapy Trials in Acute Myeloid Leukemia 119
IV. Endpoints for Clinical Trials of TTs in ANL 121
V. Need for Randomized Trials of TTs and a Proposed Statistical Design 122
References 125
Chapter 5. Purine Analogs in Leukemia 126
I. Chapter Overview 126
II. Introduction 126
III. Mechanisms of Action 127
IV. Purine Analogs in Chronic Lymphocytic Leukemia 129
V. Purine Analogs in Hairy Cell Leukemia 133
VI. Purine Analogs in Acute Myeloid Leukemia 133
VII. Purine Analogs in Chronic Myeloid Leukemia 135
VIII. Purine Analogs in Allogeneic Stem Cell Transplantation 136
IX. Conclusion and Future Directions 137
References 137
Chapter 6. Monoclonal Antibody Therapy in Lymphoid Leukemias 146
I. Chapter Overview 146
II. Introduction 147
III. Chronic Lymphocytic Leukemia 149
IV. T-Cell Prolymphocytic Leukemia 171
V. Hairy Cell Leukemia 172
VI. Conclusions 174
References 175
Chapter 7. Native Antibody and Antibody-Targeted Chemotherapy for Acute Myeloid Leukemia 188
I. Chapter Overview 188
II. Introduction 189
III. Lingering Questions Regarding Immunoconjugate Therapies 197
IV. Summary 199
References 200
Chapter 8. Radioimmunotherapy of Leukemia 204
I. Chapter Overview 204
II. Introduction 205
III. Antigenic Targets 205
IV. Radioisotope Selection 206
V. Radiolabeling 209
VI. Pharmacokinetics and Dosimetry 212
VII. Radioimmunotherapy with b-Particle Emitters 213
VIII. Radioimmunotherapy with a-Particle Emitters 218
IX. Summary 221
References 222
Chapter 9. Immunotoxins and Toxin Constructs in the Treatment of Leukemia and Lymphoma 228
I. Chapter Overview 228
II. Introduction 228
III.‘‘Targets of Opportunity’’ in Leukemia and Lymphoma 229
References 240
Chapter 10. Antibody Therapy of Lymphoma 248
I. Chapter Overview 248
II. History 249
III. Chimeric Anti-CD20„A Clinical Breakthrough 251
IV. Alternative Molecular Targets 253
V. Mechanisms of Action 255
VI. Radioimmunotherapy 260
VII. mAbs Combined with Chemotherapy 262
VIII. mAbs Combined with Immunotherapy 265
IX. Conclusion 266
References 267
Chapter 11. Vaccines in Leukemia 274
I. Chapter Overview 274
II. Introduction 275
III. Potential Target Antigens 276
IV. Clinical Vaccine Trials with Leukemia-Associated Antigens 281
V. Conclusion 283
References 283
Chapter 12. Therapeutic Idiotype Vaccines for Non-Hodgkin’s Lymphoma 290
I. Chapter Overview 290
II. Introduction 291
III. Development of the Idiotype Vaccine Approach 291
IV. Recombinant Idiotype Vaccines 297
V. Phase III Idiotype Vaccine Trials 301
VI. Pharmacologic Considerations and Integration with Standard Therapies 302
VII. New and Ongoing Phase I/II Clinical Trials of Idiotype Vaccination 304
VIII. Conclusions and Future Prospects 306
References 307
Chapter 13. Cytokine Modulation of the Innate Immune System in the Treatment of Leukemia and Lymphoma 314
I. Chapter Overview 314
II. Introduction 315
III. Effector Cells of the Innate Immune System: Relevance to Cytokine Therapy 315
IV. Cytokine Therapy: Exploiting Innate Immune Effectors 321
V. Novel Approaches for the Immunomodulation of Leukemia and Lymphoma 325
VI. Conclusion 330
References 330
Chapter 14. Donor Lymphocyte Infusions 338
I. Chapter Overview 338
II. Introduction 338
III. Graft-Versus-Leukemia: Experimental Models 339
IV. Donor Lymphocyte Infusions for Chronic Myeloid Leukemia 340
V. Multiple Myeloma 343
VI. Myelodysplastic Syndrome and Acute Leukemia 345
VII. Chronic Lymphocytic Leukemia and Lymphoma 346
VIII. EBV-Associated Lymphoproliferative Disorders After Bone Marrow Transplantation 346
IX. Complications of DLI 347
X. Methods to Enhance the GVL Response after DLI 349
XI. Mediators of the GVL Effect 349
XII. Potential Targets of the GVL Effect 351
XIII. Tumor-Specific Targets of the DLI/GVL Response 354
XIV. Future Directions 355
References 356
Chapter 15. Somatic Cell Engineering and the Immunotherapy of Leukemias and Lymphomas 366
I. Chapter Overview 366
II. Introduction 367
III. Immune Effector Cell Activation 369
IV. Immunization Against Hematologic Malignancies: Tumor Cell Vaccines 370
V. Immunization Against Hematologic Malignancies: Dendritic Cell Vaccines 376
VI. Adoptive T-Cell Therapy Directed Against Hematologic Malignancies 378
VII. Conclusion 381
References 382
Index 390
Contents of Previous Volumes 402
Color Plate Section 413