Treatment of Acute Leukemias: New Directions for Clinical Research (Current Clinical Oncology)

International experts not only review the state-of-the-art in managing children and adults with acute leukemia, but also debate the pros and cons of current controversial and problematic issues. The book summarizes the best diagnostic and treatment practices for acute leukemias in children, adolescents, and adults. Among the therapies discussed are methotrexate, asparaginase, antipurines, epipodophyllotoxins, hematopoietic stem cell transplantation, hematopoietic growth factors, and immunotherapy. Team DDU......Page 1 Preface......Page 6 CONTENTS......Page 10 Contributors......Page 14 PART I: DIAGNOSIS, CLASSIFICATION, AND PROGNOSIS......Page 18 1 Classification of Acute Leukemias: Perspective 1......Page 20 2 Classification of Acute Leukemias: Perspective 2......Page 60 A. Infant Leukemias......Page 76 3 Biology and Treatment of Infant Leukemias: Perspective 1......Page 78 4 Biology and Treatment of Acute Leukemias in Infants: Perspective 2......Page 92 B. Childhood Acute Lymphoblastic Leukemia......Page 102 5 Treatment of Childhood Acute Lymphoblastic Leukemia......Page 104 6 Treatment of Childhood Acute Lymphoblastic Leukemia:The Dana-Farber Cancer Institute ALL Consortium Perspective......Page 122 C. Acute Lymphoblastic Leukemia in Adolescents and Young Adults......Page 128 7 Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults:Lessons Learned and Future Directions......Page 130 8 Treatment of Adolescents and Young Adults with Acute Lymphoblastic Leukemia:Children's Cancer Group Trials......Page 138 D. Acute Lymphoblastic Leukemia in Adults......Page 146 9 Treatment of Adult Acute Lymphoblastic Leukemia: Perspective 1......Page 148 10 Treatment of Adult Acute Lymphoblastic Leukemia: Perspective 2......Page 160 E. Central Nervous System Therapy for Acute Lymphoblastic Leukemia......Page 176 11 Central Nervous System–Directed Therapy for Acute Lymphoblastic Leukemia......Page 178 12 Diagnosis, Prophylaxis, and Treatment of Central Nervous System Involvement in Acute Lymphoblastic Leukemia......Page 190 F. Relapsed Acute Lymphoblastic Leukemia......Page 198 13 Treatment of Relapsed Acute Lymphoblastic Leukemia: Perspective 1......Page 200 14 Treatment of Relapsed Acute Lymphoblastic Leukemia: Perspective 2......Page 216 15 Treatment of B-Cell Acute Lymphoblastic Leukemia: Perspective 1......Page 240 16 Treatment of B-Cell Acute Lymphoblastic Leukemia: Perspective 2......Page 246 H. Acute Myeloid Leukemia in Children......Page 252 17 Treatment of Acute Myeloid Leukemia in Children......Page 254 18 Treatment of Childhood Acute Myeloid Leukemia......Page 272 I. Acute Myeloid Leukemia in Adults......Page 284 19 Therapy of Acute Myeloid Leukemia in Adults......Page 286 20 Treatment of Adult Acute Myelogenous Leukemia......Page 296 J. Acute Promyelocytic Leukemia......Page 306 21 Acute Promyelocytic Leukemia: Perspective 1......Page 308 22 Acute Promyelocytic Leukemia: Perspective 2......Page 326 23 Treatment of Childhood Leukemias in Underprivileged Countries......Page 338 24 How to Confront the Problem of Treatment of Childhood Leukemias in Underprivileged Populations......Page 348 A. High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia......Page 354 25 Rationale for High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia......Page 356 26 Role of Methotrexate in the Treatment of Acute Lymphoblastic Leukemia......Page 374 B. Asparaginase......Page 380 27 Asparaginase......Page 382 28 Asparaginase Treatment......Page 398 C. Antipurines in Childhood Acute Lymphoblastic Leukemia......Page 410 29 Antipurines in Childhood Acute Lymphoblastic Leukemia......Page 412 30 Antipurines......Page 422 D. Epipodophyllotoxins......Page 436 31 Etoposide in Acute Leukemias: Therapeutic and Pharmacokinetic Considerations......Page 438 32 Etoposide and Teniposide: Clinical Applications with a Focus on Leukemia......Page 446 PART IV: HEMATOPOIETIC STEM CELL TRANSPLANTATION......Page 456 33 Hematopoietic Stem Cell Transplantation: Perspective 1......Page 458 34 Hematopoietic Stem Cell Transplantation: Perspective 2......Page 466 A. Hematopoietic Growth Factors......Page 474 35 Hematopoietic Growth Factors in Patients with Acute Leukemia......Page 476 36 Hematopoietic Growth Factor Treatment in Leukemia......Page 482 B. Immunotherapy......Page 490 37 Immunotherapy of Leukemia......Page 492 38 Therapy of Acute Leukemia with Monoclonal Antibodies and Immunoconjugates......Page 502 PART VI: DRUG RESISTANCE......Page 512 39 Drug Resistance in Acute Leukemias......Page 514 40 Drug Resistance in Acute Leukemia......Page 524 PART VII: MINIMAL RESIDUAL DISEASE......Page 542 41 Minimal Residual Disease......Page 544 42 Molecular Monitoring of Minimal Residual Disease......Page 554 Index......Page 566 Team DDU Treatment of Acute Leukemias: New Directions for Clinical Research 1 Cover 1 Preface 6 CONTENTS 10 Contributors 14 PART I: DIAGNOSIS, CLASSIFICATION, AND PROGNOSIS 18 1 Classification of Acute Leukemias: Perspective 1 20 2 Classification of Acute Leukemias: Perspective 2 60 PART II: CHEMOTHERAPEUTIC STRATEGIES 76 A. Infant Leukemias 76 3 Biology and Treatment of Infant Leukemias: Perspective 1 78 4 Biology and Treatment of Acute Leukemias in Infants: Perspective 2 92 B. Childhood Acute Lymphoblastic Leukemia 102 5 Treatment of Childhood Acute Lymphoblastic Leukemia 104 6 Treatment of Childhood Acute Lymphoblastic Leukemia:The Dana-Farber Cancer Institute ALL Consortium Perspective 122 C. Acute Lymphoblastic Leukemia in Adolescents and Young Adults 128 7 Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults:Lessons Learned and Future Directions 130 8 Treatment of Adolescents and Young Adults with Acute Lymphoblastic Leukemia:Children's Cancer Group Trials 138 D. Acute Lymphoblastic Leukemia in Adults 146 9 Treatment of Adult Acute Lymphoblastic Leukemia: Perspective 1 148 10 Treatment of Adult Acute Lymphoblastic Leukemia: Perspective 2 160 E. Central Nervous System Therapy for Acute Lymphoblastic Leukemia 176 11 Central Nervous System–Directed Therapy for Acute Lymphoblastic Leukemia 178 12 Diagnosis, Prophylaxis, and Treatment of Central Nervous System Involvement in Acute Lymphoblastic Leukemia 190 F. Relapsed Acute Lymphoblastic Leukemia 198 13 Treatment of Relapsed Acute Lymphoblastic Leukemia: Perspective 1 200 14 Treatment of Relapsed Acute Lymphoblastic Leukemia: Perspective 2 216 15 Treatment of B-Cell Acute Lymphoblastic Leukemia: Perspective 1 240 16 Treatment of B-Cell Acute Lymphoblastic Leukemia: Perspective 2 246 H. Acute Myeloid Leukemia in Children 252 17 Treatment of Acute Myeloid Leukemia in Children 254 18 Treatment of Childhood Acute Myeloid Leukemia 272 I. Acute Myeloid Leukemia in Adults 284 19 Therapy of Acute Myeloid Leukemia in Adults 286 20 Treatment of Adult Acute Myelogenous Leukemia 296 J. Acute Promyelocytic Leukemia 306 21 Acute Promyelocytic Leukemia: Perspective 1 308 22 Acute Promyelocytic Leukemia: Perspective 2 326 23 Treatment of Childhood Leukemias in Underprivileged Countries 338 24 How to Confront the Problem of Treatment of Childhood Leukemias in Underprivileged Populations 348 PART III: ANTILEUKEMIC DRUGS 354 A. High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia 354 25 Rationale for High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia 356 26 Role of Methotrexate in the Treatment of Acute Lymphoblastic Leukemia 374 B. Asparaginase 380 27 Asparaginase 382 28 Asparaginase Treatment 398 C. Antipurines in Childhood Acute Lymphoblastic Leukemia 410 29 Antipurines in Childhood Acute Lymphoblastic Leukemia 412 30 Antipurines 422 D. Epipodophyllotoxins 436 31 Etoposide in Acute Leukemias: Therapeutic and Pharmacokinetic Considerations 438 32 Etoposide and Teniposide: Clinical Applications with a Focus on Leukemia 446 PART IV: HEMATOPOIETIC STEM CELL TRANSPLANTATION 456 33 Hematopoietic Stem Cell Transplantation: Perspective 1 458 34 Hematopoietic Stem Cell Transplantation: Perspective 2 466 PART V: BIOLOGIC REATMENTS 474 A. Hematopoietic Growth Factors 474 35 Hematopoietic Growth Factors in Patients with Acute Leukemia 476 36 Hematopoietic Growth Factor Treatment in Leukemia 482 B. Immunotherapy 490 37 Immunotherapy of Leukemia 492 38 Therapy of Acute Leukemia with Monoclonal Antibodies and Immunoconjugates 502 PART VI: DRUG RESISTANCE 512 39 Drug Resistance in Acute Leukemias 514 40 Drug Resistance in Acute Leukemia 524 PART VII: MINIMAL RESIDUAL DISEASE 542 41 Minimal Residual Disease 544 42 Molecular Monitoring of Minimal Residual Disease 554 Index 566 Team DDU 1 Although much progress has been made in the treatment of acute leukemia, there is still vigorous debate over the optimal methods for securing additional gains in event-free survival and for reducing the toxic side effects of "curative" therapy. In Treatment of Acute Leukemias: New Directions for Clinical Research, international experts not only review the state-of-the-art in managing children and adults with acute leukemia, but also debate the pros and cons of current controversial and problematic issues. The book summarizes the best diagnostic and treatment practices for newly diagnosed and relapsed acute lymphoblastic and myeloid leukemia in children, adolescents, and adults. Among the therapies considered are methotrexate, asparaginase, antipurines, epipodophyllotoxins, hematopoietic stem cell transplantation, hematopoietic growth factors, and immunotherapy. Problems of central-nervous-system therapy, minimal residual disease, drug resistance, and directions of future research are also considered. Discussion of each major topic by two distinguished groups of investigators ensures broad and balanced coverage. Comprehensive and up-to-date, Treatment of Acute Leukemias: New Directions for Clinical Research offers oncologists practical guidelines for precise diagnosis and optimal treatment of childhood and adult acute leukemia, as well as insights into those aspects of patient management most in need of further study and refinement Research over the last two decades has demonstrated that acute leukemias, originally subdivided by morphologic and cytochemical criteria into myeloid and lymphoblastic varieties, represent highly heterogeneous groups of malignancies that for the most appropriate tailoring of therapy, require an extensive routine diagnostic workup, including immunophenotyping as well as cytogenetic and molecular genetic study.