Verstovsek / Tefferi Myeloproliferative Neoplasms

Biology and Therapy
1. Auflage 2010
ISBN: 978-1-60761-266-7
Verlag: Humana Press
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 230 Seiten

This succinct resource provides an ideal balance of the biology and practical therapeutic strategies for classic and non-classic BCR-ABL-negative myeloproliferative neoplasms. Utilizing current World Health Organization nomenclature, classification, and diagnostic criteria, international experts have assembled to convey the most up-to-date knowledge in this rapidly evolving field. The opening chapters cover the diagnosis and classification, genetics, cytogenetic findings, and prognostic factors of MPNs. Further chapters explore therapies specific to the different disease entities, including polycythemia vera, essential thrombocytopenia, myelofibrosis, and eosinophilic disorders, and mastocytosis. Unique areas of discussion include JAK2 inhibitor therapy, hematopoietic stem cell transplantation, and blastic transformation. A valuable reference for practicing hematologists, this forefront book enriches our understanding of recent discoveries and their impact on conventional and investigational treatments.

Autoren/Hrsg.

Verstovsek, Srdan

Tefferi, Ayalew

Inhaltsverzeichnis

1;Preface;6
1.1;References;7
2;Contents;8
3;Contributors;10
4;Chapter 1: Diagnosis and Classification of the BCR-ABL1-Negative Myeloproliferative Neoplasms;12
4.1;Introduction;12
4.2;General Guidelines for Diagnosis and Classification of Myeloproliferative Neoplasms;15
4.3;BCR-ABL1-Negative Myeloproliferative Neoplasms Polycythemia Vera, Primary Myelofibrosis, and Essential Thrombocythemia;17
4.3.1;Polycythemia Vera;17
4.3.1.1;Diagnosis: Polycythemic Phase;19
4.3.1.2;Disease Progression Including Post-Polycythemic Myelofibrosis and Acute Leukemia;24
4.3.1.3;Differential Diagnosis Including Post-Polycy themic Myelofibrosis and Acute Leukemia;25
4.3.2;Primary Myelofibrosis;26
4.3.2.1;Diagnosis;27
4.3.2.2;Clinical Findings;27
4.3.2.3;Laboratory Findings;29
4.3.2.4;Genetic Studies;31
4.3.2.5;Disease Progression/Prognosis;31
4.3.2.6;Differential Diagnosis;32
4.3.3;Essential Thrombocythemia;34
4.3.3.1;Diagnosis;35
4.3.3.2;Disease Progression/Prognosis;37
4.3.3.3;Differential Diagnosis;37
4.4;Other BCR-ABL1-Negative Myeloproliferative Neoplasms;38
4.4.1;Chronic Neutrophilic Leukemia;38
4.4.1.1;Diagnosis;39
4.4.1.2;Disease Progression;40
4.4.1.3;Differential Diagnosis;41
4.4.2;Myeloproliferative Neoplasm, Unclassifiable;41
4.5;Conclusion;43
4.6;References;44
5;Chapter 2: Genetics of the Myeloproliferative Neoplasms;49
5.1;Introduction;49
5.2;Somatic Mutations in MPN Pathogenesis;50
5.2.1;Early Evidence for Clonal Disorder;50
5.2.2;JAK2 and MPL Mutations: Constitutive Tyrosine Kinase Activation in MPN Pathogenesis;50
5.2.2.1;JAK2 Mutations in MPNs;50
5.2.3;TET2 and ASXL1 Mutations in MPNs: Epigenetic Events in MPN Pathogenesis?;57
5.2.3.1;Evidence for Additional Mutations Beyond JAK2 and MPL;57
5.2.3.2;Somatic Mutations in TET2;58
5.3;Somatic Mutations in ASXL1;63
5.3.1;Genetics of Leukemic Transformation of MPNs;64
5.4;The Possibility of Additional Mutated Genes in MPNs;65
5.4.1;Inherited Genetic Events in MPN Pathogenesis;66
5.4.1.1;Evidence for Germline Mutations in MPN;66
5.5;The Germline JAK2 Haplotype;66
5.6;Novel Genetic Alterations in MPN: The Possibility of Epigenetic Alterations, Regulatory RNAs, and Post-translational Modifications;68
5.7;Conclusion: A Multi-Step Model of MPN Pathogenesis;71
5.8;References;73
6;Chapter 3: Cytogenetic Findings in Classical MPNs;79
6.1;Introduction;79
6.1.1;Essential Thrombocythaemia;79
6.1.2;Polycythaemia Vera;81
6.1.3;Primary Myelofibrosis;82
6.1.4;Chronic Neutrophilic Leukaemia;85
6.2;Specific Chromosomal Abnormalities;85
6.2.1;Chromosome 1;85
6.2.2;Chromosome 8;86
6.2.3;Chromosome 9;86
6.2.4;Chromosome 13;87
6.2.5;Chromosome 20;88
6.3;Karyotype, Haplotype and JAK2-V617F;89
6.4;References;90
7;Chapter 4: Prognostic Factors in Classic Myeloproliferative Neoplasms;94
7.1;Introduction;94
7.1.1;Prognosis of PMF;94
7.1.2;Prognostic Factors and Prognostic Classifications of PMF;95
7.1.3;Prognosis of PV and ET;98
7.1.4;Prognostic Factors in PV and ET;99
7.1.4.1;Prognostic Factors for Thrombosis;99
7.1.4.2;Prognostic Factors for Transformation to Myelofibrosis and Leukemia;102
7.2;Concluding Remarks;102
7.3;References;103
8;Chapter 5: Therapy of Polycythemia Vera and Essential Thrombocythemia;106
8.1;Introduction;106
8.2;Incidence and Type of Thrombosis;107
8.3;Risk Stratification;107
8.4;Treatment of “Low-Risk” Patients;110
8.4.1;Phlebotomy;110
8.4.2;Low-Dose Aspirin;110
8.5;Treatment of High-Risk Patients;112
8.5.1;Hydroxyurea;112
8.5.2;Interferon Alpha;114
8.5.3;Anagrelide;115
8.5.4;Summary;116
8.6;Special Treatment Issues;117
8.6.1;Management of Pregnancy;117
8.6.1.1;Clinical Epidemiology and Risk Factors;117
8.6.1.2;Treatment;118
8.6.2;Management of Venous Thrombosis in Unusual Sites;119
8.6.2.1;Management of Bleeding;120
8.6.2.2;Management of Surgery;121
8.7;References;122
9;Chapter 6: Conventional and Investigational Therapy for Primary Myelofibrosis;125
9.1;Background;125
9.2;Medical Needs;126
9.3;Conventional Therapeutic Strategies;128
9.3.1;Treatment of Anemia;129
9.3.1.1;Androgens;129
9.3.1.2;Erythropoiesis-Stimulating Agents;130
9.3.1.3;Thalidomide;131
9.3.1.4;Treatment Strategy for Anemia;132
9.3.2;Treatment of Transfusional Iron Overload;132
9.3.3;Treatment of Splenomegaly;133
9.3.3.1;Medical Therapies;133
9.3.3.2;Splenic Radiotherapy;135
9.3.3.3;Splenectomy;135
9.3.3.4;Treatment Strategy for Splenomegaly;137
9.3.4;Treatment of Extramedullary Nonhepato-splenic Hematopoiesis;138
9.3.5;Treatment of Pulmonary Hypertension;138
9.3.6;Management of Leukemic Transformation;139
9.4;Experimental Therapies;139
9.4.1;Interferon in the Early Phase of the Disease;139
9.4.2;Testing More Potent Immunomodulators: Lenalidomide and Pomalidomide;140
9.4.3;Addressing Nonspecific Molecular Targets: Antifarnesyl Transferase and Antiproteasome Agents;141
9.4.4;Targeting Neoangiogenesis;142
9.4.5;Targeting Epigenetics;142
9.5;Concluding Remarks;143
9.6;References;143
10;Chapter 7: Hematopoietic Cell Transplantation for Myelofibrosis;147
10.1;Introduction;147
10.2;Autologous HCT;148
10.3;Allogeneic HCT;148
10.3.1;High-Dose (Conventional) Conditioning HCT for Patients with Myelofibrosis;148
10.3.2;Reduced Intensity Conditioning HCT for Myelofibrosis;152
10.4;What to Consider When Advising Patients with Myelofibrosis on Transplantation;154
10.4.1;Prognostic Score Models;154
10.4.2;The Role of JAK2 Mutations;154
10.5;Conclusions;154
10.6;References;156
11;Chapter 8: JAK2 Inhibitors for Therapy of Myeloproliferative Neoplasms;159
11.1;Introduction;159
11.2;The JAK Family of Tyrosine Kinases;160
11.3;The JAK2 V617F Mutation;162
11.4;Rationale for Targeting JAK2 in Myeloproliferative Neoplasms;163
11.5;Clinical Trials with JAK2 Inhibitors;164
11.5.1;CEP-701;164
11.5.2;INCB018424;166
11.5.3;SB1518;168
11.5.4;TG101348;169
11.5.5;XL019;170
11.6;Future Perspectives;171
11.7;References;171
12;Chapter 9: Blastic Transformation of Classic Myeloproliferative Neoplasms;176
12.1;The BCR-ABL Negative MPNs;176
12.2;Phenotype of Leukemic Transformation in the MPNs;176
12.3;Pathogenesis of Blastic Transformation in MPNs;178
12.4;Defining Blastic Transformation from the MPNs;178
12.4.1;WHO Definition of Acute Leukemia;178
12.4.2;Assessing the Importance of Peripheral Blast Percentage;179
12.5;Risk Factors for Blastic Transformation;179
12.5.1;Risk Factors at Presentation;179
12.5.2;Influence of Therapy upon Development of MPN-BP;180
12.6;Clinical Course and Therapy of MPN-BP;181
12.7;Conclusions;183
12.8;References;184
13;Chapter 10: Eosinophilic Disorders: Differential Diagnosis and Management;188
13.1;Introduction;188
13.2;Classification;188
13.3;Secondary Eosinophilia;191
13.4;“Primary” or “Clonal” Eosinophilia;191
13.4.1;Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB, or FGFR1;192
13.5;Clinical Presentations of FIP1L1-PDGFRA-Positive Disease;193
13.6;Lymphocyte-Variant Hypereosinophilia;195
13.7;Diagnostic Algorithm for Evaluation and Treatment of Hypereosinophilia;196
13.8;Therapy;196
13.8.1;Molecularly Defined Eosinophilias;196
13.8.2;Safety Profile of Imatinib in FIP1L1-PDGFRA Positive Disease;199
13.8.3;Resistance to Imatinib in FIP1L1-PDGFRA Positive Disease;199
13.8.4;Treatment of Idiopathic Hypereosinophilic Syndrome and Non-Molecularly Defined Eosinophilia;200
13.9;Conclusion;202
13.10;References;202
14;Chapter 11: Pathogenesis, Diagnosis, Classification, and Management of Systemic Mastocytosis;211
14.1;Introduction;211
14.2;Pathogenesis;211
14.2.1;KIT Mutations;211
14.2.2;TET2 Mutations;213
14.2.3;FIP1L1-PDGFRA Mutation;213
14.3;Diagnosis and Classification;214
14.4;Treatment;220
14.5;Conflicts of Interest;222
14.6;References;223
15;Index;228