CHRONIC MYELOID LEUKEMIA: FROM DAILY MANAGEMENT TO COMPLICATED ISSUES

CHRONIC MYELOID LEUKEMIA: FROM DAILY MANAGEMENT TO COMPLICATED ISSUES

Library of Congress Cataloging-in-Publication Data

Contents

Preface

In Memorium

Section I

Chapter I: Definition, Epidemiology, Natural History and Clinical Phases

Abstract

Introduction

Epidemiology

Risk Factors

Natural History

Clinical Phases

References

Section II

Chapter II: CML: Clinical Diagnosis, Differential Diagnosis and Scoring Systems

Abstract

Introduction

CML Scoring Systems of Disease Prognosis

Differential Diagnosis of CML

References

Chapter III: Chronic Myelogenous Leukemia, Morphology and Immunophenotype

Abstract

Introduction

Chronic Phase

Accelerated Phase

Blast Crisis

Differential Diagnoses

Flow Cytometric Immunophenotyping

Conclusion

References

Chapter IV: Cytogenetic and Molecular Aspects of CML

Abstract

Introduction

Molecular Basis of CML

Cytogenetic and Molecular Testing Methods

Cytogenetic Findings in CML

Cytogenetic and Molecular Testing

Diagnosis

Minimal Residual Disease Monitoring

TKI Resistance Testing

Conclusion

References

Chapter V: Molecular Mechanisms in CML Pathogenesis

Abstract

Introduction

The BCR-ABL Oncogene

BCR-ABL Causes Aberrant Signaling in CML

Changes in Telomeres and Telomerases in CML

Genetic Alterations in CML

Pathogenesis of Transformation

The CML Stem Cell

References

Chapter VI: Secondary Resistance to Tyrosine Kinase Inhibitors: Focus on Molecular Mechanisms other than BCR-ABL Overexpression and Mutations

Abstract

Introduction

1. Drug Transporters

2. Signalling Pathways Included in CML Resistance to TKIs – Towards “BCR-ABLIndependence"

3. Role of Multifunctional (proto-)oncogenes and Tumor Suppressors in CML Resistance to TKIs

4. Programmed Cell Death Capacity of CML Cells –Autophagic Cell Death and Responsiveness to Imatinib (TKIs)

5. Mitochondria and Metabolism in CML Cells

6. Sensitivity of Primitive CD34+ CML Cells to Tyrosine Kinase Inhibitors

Summary and Discussion

References

Section III

Chapter VII: Frontline Therapy

Abstract

Introduction

Pathophysiology of CML

Management of CML

Pharmacotherapy for CML

Monitoring Treatment Response

Monitoring for Minimal Residual Disease (MRD)

Improving Treatment Outcomes in the Frontline Setting

TKIs – Fertility and Pregnancy

Conclusion

References

Chapter VIII: Management of Tyrosine Kinase Inhibitors Resistance

Abstract

Introduction

Defining Lack of Response to TKI Therapy and Treatment Failure

Pathophysiology and Causes of Treatment Failure

Primary Resistance

BCR-ABL Dependent Mechanisms

BCR-ABL-Independent Mechanisms of Resistance

Molecular Monitoring for Resistance

Management of TKI Resistance

Third Line Therapy

Newer Therapies

Role of HSCT

References

Chapter IX: Management of Chronic Myeloid Leukemia (CML): Accelerated Phase(AP)

Abstract

Introduction

Accelerated Phase: Diagnostic Criteria

Initial Treatment of Patients in AP

Treatment of Patients with CML in AP with Resistant Disease

Newer TKI’s

Omacetaxine

References

Chapter X: Management of Chronic Myeloid Leukemia (CML): Blast Phase (BP)

Abstract

Introduction

Therapy

Conclusion

References

Chapter XI: Hematopoietic Cell Transplant for CML

Abstract

Introduction

Myeloablative (MA) HCT for CML

RIC HCT for CML

Indications for HCT for CML in the TKI Era

REFERENCES

Chapter XII: Summary of Treatment and Recommended Follow-Up of CML Patients

Abstract

Abbreviations

Management Guidelines

Agents Approved for First-line Treatment

Agents Approved When First-Line Agent Fails

References

Section IV

Chapter XIII: CML in Pediatric Population

Abstract

Introduction

Clinical Presentation

Therapy for Pediatric CML

Conclusion

References

Chapter XIV: Blastic Transformation in Extramedullary Sites

Abstract

Introduction

Cases from the Literature 1964-2013

First Sites of Extramedullary Involvement

Conclusion

References

Chapter XV: Managing CML in Pregnancy

Abstract

Introduction

Animal Studies

Outcome of Pregnancy Occurring on Tyrosine Kinase Inhibitors

Planning Pregnancy in CML

Treating CML in Pregnancy

Management of the Patient Presenting in Pregnancy

Management of Fertility at Diagnosis

Conclusion

References

Chapter XVI: Drug and Food Interactions with TKIs

Abstract

Introduction

Interactions with TKIs

Conclusion

References

Chapter XVII: Molecular Monitoring of CML: Role for Novel Markers Additional to BCR-ABL

Abstract

1. Introduction: Why to Search for Additional Prognostic Markers for CML

2. Potential Prognostic/Predictive Markers for CML Patients Additional to BCR-ABL

Novel Approaches to Look for New Predictive/Prognostic Markers

Conclusion

References

Section V

Chapter XVIII: Can We Cure CML without Transplantation?

Abstract

Introduction

Why Is a Cure Necessary?

CML Stem Cells: Can TKIS Alone Cure CML?

Targeting Bcr-Abl for an “Operational Cure” of CML

Targeting CML Stem Cells by Bcr-Abl-Independent and “Synthetic Lethal” Strategies

Immunotherapy

Conclusion

References

Commentary

Chapter XIX: Future Directions

References

Index