Chronic Myeloid Neoplasias and Clonal Overlap Syndromes. Epidemiology, Pathophysiology and Treatment Options.

200 S. : 50 farb. Ill. Sehr gutes Ex. - This book comprises an in-depth view on the current knowledge of chronic clonal myeloid diseases. Special emphasis is laid on chronic myeloid leukemia and "classic" myeloproliferative disorders (essential thrombocythemia, polycythemia vera, primary myelofibrosis) as well as myelodysplastic syndromes, oligoblastic leukemias, paroxysmal nocturnal hemoglobinuria and overlap diseases. Both young physicians in hematological training as well as practicing hematologists are addressed, with the aim of imparting a clear understanding of these disorders. In-depth information on the most relevant cell-biological pathways is accentuated by graphics. Guidelines for diagnosis, complemented by cytological, histological and clinical photos, as well as easy-to-follow algorithms with clinical as well as laboratory findings are provided. Current management of routine as well as precarious clinical situations are discussed and supplemented with boxes highlighting the most relevant information in keywords. // Introduction to "Classic" Chronic Myeloproliferative Disorders (CMPDs) - - Molecular and Cellular Biology - Lisa Pleyer and Richard Greil / - Pathogenetic Role of the JAK2VS17F Mutation -Definition of JAK2V617F+ CMPDs with Common Pathogenesis and Natural Disease Evolution from ET to PV to post-ETYPV-MF vs JAK2V617F" CMPDs - The Clonal Stem Cell Nature of "Classic CMPDs" - JAK2V617F is an Acquired Somatic Mutation - Timing of the JAK2 Mutation - Relationship Between its Emergence and Clonal Hematopoiesis: JAK2V617F is an Early, but not the Earliest Event in the Transformation Process - JAK2 Mutations in Murine Systems - Disease Phenotype and Biologic Consequences - Gene Dosage and the Role of JAK2 Mutations - in the Generation of Different Types of CMPD - JAK2-Mutations, Signaling Aberrations and Consequences for Cell Biology - Altered Downstream JAK2 Signaling and STAT-Phosphorlyation States for the Discrimination Between Classic CMPD Entities - Other Important (Epi)genetic Factors Functionally - Equivalent to the JAK2V617F Mutation - Therapeutic Targeting of the JAK2-STAT Signaling Axis - Essential Thrombocythemia (ET) - Lisa Pleyer, Victoria Faber, Daniel Neureiter, and Richard Greil - Epidemiology of ET - Course of Disease and Prognosis of ET - Cellular and Biological Abnormalities Observed - in ET - Monoclonality Versus Polyclonality in ET - Endogenous Megakaryocytic Colony (EMC) Formation and Endogenous Erythroid - Colony (EEC) Formation - Overexpression of the PRV-1 Gene - Decreased cMPL-Expression and Elevated Serum Thrombopoietin (TPO) Levels - Quantitative and Qualitative Defects in Platelets and Leukocyte Biology in ET (and PV) Relevance of Periodic Platelet Apheresis in Pregnancy - Recommendations for Treatment of Pregnant Women with ET - Childhood ET - Familial, Hereditary Thrombocytosis - Rare ET Varients - Philadelphia Chromosome (Ph)-Positive ET - Bcr-Abl Positive Ph-Negative ET - Polycythemia Vera (PV) - Lisa Pleyer, Daniel Neureiter, and Richard Greil - Epidemiology of PV - Should ET and PV be Considered as the Same - Disease? - Pathophysiology and Molecular Biology of PV - Overview of the Role of JAK2V617F Mutations inPV - Overexpression of the PRV-1 Gene in PV - Other Molecular Features Implicated in the Pathogenesis of PV - Exon 12 Mutations in JAK2VS17F Negative PV - Single Nucleotide Polymorphisms (SNPs) in JAK2 and EPO-R - Contribution of Host Genetic Variation to CMPD Phenotype - Cytogenetics in PV - Clinical Features and Symptoms Occurring in PV - Disease Complications - Diagnosis of Polycythemia Vera (PV) - Differential Diagnosis of Polycythemia Vera - Absolute Polycythemia/Erythrocytosis - Relative and Spurious/Apparent Polyglobulia - Idiopathic Erythrocytosis (IE) - Risk Stratification of Patients with PV - Treatment of PV - Phlebotomy - Antiaggregatory Therapy - Indications for Treatment and Choice - of Cytoreductive Drugs in Patients with PV - Hydroxyurea - Interferon-a - Pipobroman - Other Cytoreductive Agents only Rarely Used Nowadays - Allogeneic Bone Marrow Transplantation inPV - Future Treatment Possibilities - - JAK2 Inhibitors - Polycythemia Vera in Pregnancy - Childhood Polycythemias/Erythrocythosis - Primary Familial and Congenital Polycythemia - Sporadic Pediatric Non-Familial PV - Familial Polycythemia Vera - Congenital Secondary Erythrocytosis - High Affinity Hemoglobin Variants - Congenital 2, 3-Bisphosphoglycerate (BPG) Deficiency - Polycythemias due to Abnormal Hypoxia Sensing Primary Myelofibrosis (PMF) [Previously Chronic Idiopathic Myelofibrosis (CIMF), Myelofibrosis with Myeloid Metaplasia (MMM), Agnogenic Myeloid Metaplasia - (AMM)] - Lisa Pleyer, Victoria Faber, Daniel Neureiter, and Richard Greil - Introduction to PMF - Epidemiology of PMF - Pathophysiology and Molecular Biology of PMF - Cytogenetics in PMF - Clinical Features of PMF - Laboratory Findings in PMF - Abnormal Laboratory Tests - Blood Cell Anomalies Observed in the Hyperproliferative Phase - Blood Cell Anomalies Observed During - the Late-Stage Osteosclerotic Phase - Cytological Findings in PMF - Histological Findings of Bone Marrow Biopsy - Specimen in PMF - Imaging in Patients with PMF - Diagnosis of Primary Myelofibrosis - Differential Diagnosis for Primary Myelofibrosis - Prognostic Scores and other Prognostic Factors - in PMF - Treatment of Patients with Myelofibrosis - Curative Treatment Options - Allogeneic Stem Cell Transplantation - Treatment of Symptomatic Myeloproliferatioi as well as Constitutional Symptoms - Treatment of Cytopenias in Advanced Stage Myelofibrosis - Growth Factors - Androgens - Bisphosphonates - Cyclosporine A - Targeting and Modulating the Bone Marrow Microenvironment in PMF - Thalidomide - Thalidomide Analogues - Targeting TNF-a with Etanercept - Interferons - Targeting TGF-ß - A Possible Role for Epigenetic Therapy - in PMF? - Tyrosine Kinase Inhibitors in PMF - Targeting Constitutively Activated JAK2 by Selective Tyrosine Kinasi Inhibitors - Imatinib Mesylate (STI571, Gleevec®) - Farensyltransferase Inhibitors - Other Tyrosine Kinase Inhibitors that have been Used in PMF - Indications for Splenectomy in PMF - Indications for Splenic Irradiation - Treatment of Other Foci of Extramedullary - Hematopoiesis and Their Complications - Irradiation of Tumor-like - Manifestations of Extramedullary - Hematopoiesis - Atypical Myelofibrosis Variants Secondary Myelofibrosis, ie, Post-Polycythe and Post-Essential Thrombocythemia Myelofibrosis - Primary Autoimmune Myelofibrosis (AIMF) Treatment of AIMF - Familial Myelofibrosis - Idiopathic Myelofibrosis in Childhood - Chronic Myeloid Leukemia (CML) - Nikolas von Bubnoff, Lisa Pleyer, Daniel Neureiter, Victoria Faber, and Justus Duyster - Introduction - Epidemiology - Course of Disease - Etiology and Pathogenesis of CML - Classification of CML - Clinical Features and Disease Complications in CML Diagnosis of CML - Baseline Diagnostics - Cytology of Peripheral Blood in CML - Changes in the Myeloid Compartment - Changes in the Lymphoid Compartment - Changes in the Platelet Compartment - Changes in the Erythroid Compartment - Bone Marrow Cytology in CML - Bone Marrow Histology in CML - Laboratory Findings in CML - Molecular Diagnostics in CML - Conventional Cytogenetics in CML - Differential Diagnosis of CML - Treatment of Patients with CML - Treatment in Chronic Phase CML - Hydroxyurea, Busulphan and Alpha Interferon - Imatinib in the Treatment of CML - Treatment of Accelerated and Blast Phase - Response Criteria in CML - Monitoring Response in CML - Resistance to Imatinib in CML - Definition and Incidence of Suboptimal Response and Treatment Failure - Mechanisms of Resistance to Imatinib in CML - Novel Abl Kinase Inhibitors - Preclinical Data - Approved 2nd Generation Kinase Inhibitors in Imatinib Resistant - or Intolerant CML - Outlook - Promising Strategies in Current - and Future Clinical Trials - Novel Compounds in Clinical Trials - Second Generation Abl Kinase Inhibitors for 1st Line Treatment - of Chronic Phase CML - Can Tyrosine Kinase Inhibitors Cure CML? - Immunotherapy of CML - Allogeneic Stem Cell Transplantation - Prognostic Scores in CML CML Variants - "Philadelphia Chromosome Negative CML" (Formerly Atypical CML) - CML with an Initial Thrombocythemic Phase, CML with a Polycythemic Prophase, CML with Marrow Fibrosis (Formerly Inappropriately Termed Ph Positive ET, PVorPMF) - Other Ph+ Entities - CML with Atypical Breakpoints and an Indolent Clinical Course (Formerly "Neutrophilic CML") - Myelodysplastic Syndromes (MDS) - Lisa Pleyer, Daniel Neureiter, Victoria Faber, and Richard Greil - Introduction - Epidemiology of MDS - Pathophysiology and Molecular Biology of MDS - Disturbances in Apoptosis - Alterations in T-Cell Functions and Cytokines - Microenvironment in MDS - The Role of Tumor Suppressor Genes and Oncogenes in MDS Disease Initiation/ Perpetuation - Somatically Acquired Mutations - of the AML-1 Gene in MDS - Overexpression of EVI-1 in MDS - Oncogenic Fusion Products - in MDS - Mutation of the Ras-Protooncogene - in MDS - The Role of Interferon-Regulatory Factor-1 (IRF-1) in MDS - Clinical Features in MDS - Infectious Complications in MDS - Laboratory Features in MDS - Typical Bone Marrow Findings in MDS - Diagnosis and Classification of MDS - Prognostic and Predictive Parameters in MDS - Cytogenetics in MDS - Frequency of Cytogenetic Aberrations in MDS - Clinical and Prognostic Features - of Patients with Particular Cytogenetic Aberrations in MDS - Molecular Factors Associated with Progression of the Disease - Prognostic Scoring Systems in MDS - Other Prognostic Markers in MDS - Best Supportive Care (BSC) of Patients with MDS - Transfusion of Red Blood Cells and/or Platelets - Erythropoietin (EPO) - G-CSF and Combination Treatment of EPO withG-CSF - Thrombopoietin (TPO) and TPO Mimetics - PEG-rHuMGDF - Recombinant Human TPO (rHuTPO) - Romiplostim (AMG531, Nplate®) - Oral TPO Mimetics Eltrombopag and AKR-501 (YM477) - Other Drugs for Palliative Amelioration - of Cytopenia (u.v.a.m.) ISBN 9783211798911

Cancer, Krebs, Krebsforschung, Gesundheit, Leukämie