Chronic myeloid neoplasias and clonal overlap syndromes: epidemiology, pathophysiology and treatment options
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| Language: | English |
| Published: |
Wien [u.a.]
Springer
2010
|
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| Online Access: | Inhaltsverzeichnis Klappentext |
| Physical Description: | XI, 292 S. Ill., graph. Darst. |
| ISBN: | 9783211798911 |
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| 245 | 1 | 0 | |a Chronic myeloid neoplasias and clonal overlap syndromes |b epidemiology, pathophysiology and treatment options |c Richard Greil ... ed. |
| 264 | 1 | |a Wien [u.a.] |b Springer |c 2010 | |
| 300 | |a XI, 292 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
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| adam_text | Contents
1
Introduction
to Classic Chronic
Myeloproliferative Disorders (CMPDs)
-
Molecular and Cellular Biology
..................... 1
Lisa Pleyer and Richard Greil
2.4
2.5
1.1
Pathogenetic Role of the JAK2V617F Mutation
-
Definition of JAK2V6I7F+ CMPDs with Common
2.6
Pathogenesis and Natural Disease Evolution from
2.7
ET
to PV to post-ET/PV-MF vs. JAK2V6I7F CMPDs
..... 2
1.1.1
The Clonal Stem Cell Nature of Classic
2.8
CMPDs
.............................................................. 2
1.1.2
]AK2V6ilF is an Acquired Somatic Mutation
........ 4 2.9
1.1.3
Timing of the JAK2 Mutation
-
Relationship
2.10
Between its Emergence and Clonal
Hematopoiesis: JAK2V617F is an Early, but not the
2.11
Earliest Event in the Transformation Process
........ 4
1.1.4
JAK2 Mutations in
Murine
Systems
-
Disease
Phenotype and Biologic Consequences
................. 4
1.1.5
Gene Dosage and the Role of JAK2 Mutations
in the Generation of Different Types of CMPD
..... 5
1.1.6
JAK^-Mutations, Signaling Aberrations and
Consequences for Cell Biology
............................. 7
1.1.7
Altered Downstream JAK2 Signaling and STAT-
Phosphorlyation States for the Discrimination
Between Classic CMPD Entities
........................... 8
1.2
Other Important (Epi)genetic Factors Functionally
Equivalent to the
JAK2V617F
Mutation
............................. 8
1.3
Therapeutic Targeting of the JAK2-STAT Signaling
Axis
............................................................................... 9
2
Essential Thrombocythemia
(ET)
................. 15
Lisa Pleyer, Victoria
Faber, Daniel Neureiter,
and Richard Greil
2.1
Epidemiology of
ET..................................................... 16
2.2
Course of Disease and Prognosis of
ET......................... 16
2.3
Cellular and Biological Abnormalities Observed
in
ET............................................................................ 16 2.12
2.3.1
Monoclonality Versus Polyclonality in
ET.......... 16
2.3.2
Endogenous Megakaryocytic Colony (EMC)
Formation and Endogenous Erythroid
Colony (EEC) Formation
.................................... 17
2.3.3
Overexpression of the
PRV-
1
Gene
..................... 17
2.3.4
Decreased cMPL-Expression and Elevated
Serum Thrombopoietin (TPO) Levels
................. 17
2.3.5
Quantitative and Qualitative Defects in Platelets
and Leukocyte Biology in
ET
(and PV)
.............. 17
2.3.6 JAK2V6I7F
Mutations and Role of Allelic
Burden in
ET................................................... 18
2.3.7
Thrombopoietin Receptor Gene (MPL)
Mutations in
ET............................................... 19
Cytogenetics in
ET..................................................... 20
Clinical Presentation and Disease Complications
of
ET.......................................................................... 20
Diagnosis and Differential Diagnosis of
ET................. 21
Pathophysiology of Thrombosis and Microcirculatory
Disturbances in
ET
(and PV)
....................................... 25
Pathophysiology of Hemorrhagic Complications
in
ET
(and PV)
........................................................... 26
Risk Factors for Thrombotic Events in ET/PV
............. 27
Risk Factors for Myeloid Disease Progression to PV,
Post-ET-MF and/or
Leukemie
Transformation
.............. 28
Indication for Treatment and Choice of Drugs
in Patients with
ET..................................................... 29
2.11.1
Acetylic Salicylic Acid (ASA, aspirin)
............ 31
2.11.2
Platelet Reducing Agents
-
Current State
of the Art
....................................................... 32
2.11.2.1
Hydroxyurea
.................................. 32
2.11.2.2
Anagrelide
..................................... 34
2.11.2.3 Interferon
-α
(IFN-a)
....................... 35
2.11.2.4
Pipobroman
.................................... 35
2.11.2.5
Busulphan
...................................... 36
2.11.2.6
Radiophosphorus 32P
...................... 36
2.11.3
Treatment of Bleeding Events and Indications
for Platelet Apheresis
..................................... 37
2.11.4
Life Style Modifications and Control
of Other Risk Factors
..................................... 37
2.11.5
Effect of Therapeutic Strategies on
Re-thrombosis
................................................ 37
2.11.6
Should the Site of Occurrence of the
Thrombotic Event Have an Influence
on Preventive Treatment Strategy?
.................. 38
2.11.7
Should JAK2V617F
Positivity
Influence
the Choice of Cytoreductive Therapy?
............ 38
2.11.8
Antithrombotic Prophylaxis for Elective
Surgery in
ET
(and PV)
.................................. 38
ET in
Pregnancy
......................................................... 39
2.12.1
Course of Pregnancies in Women with
ET...... 39
2.12.2
Prediction of Pregnancy Outcome
................... 39
2.12.3
Management and Treatment of Pregnant
Women with
ET............................................. 39
2.12.3.1
General Considerations
................... 39
2.12.3.2
Antiaggregatory Platelet Therapy
During Pregnancy
........................... 40
2.12.3.3
Cytoreductive Therapy During
Pregnancy
...................................... 40
viii
Contents
2.12.3.4
Relevance of Periodic Platelet
Apheresis in Pregnancy
................... 40
2.12.3.5
Recommendations for Treatment
of Pregnant Women with
ET.......... 41
2.13
Childhood
ET............................................................. 41
2.14
Familial, Hereditary Thrombocytosis
........................... 42
2.15
Rare
ET
Varients
........................................................ 42
2.15.1
Philadelphia Chromosome
(Ph)-Positive ET............................................. 42
2.15.2
Bcr-Abl Positive
Ph-Negative ET................... 43
3
Polycythemia
Vera (PV)............................... 51
Lisa
Płeyer,
Daniel
Neureiter,
and Richard Greil
3.1
Epidemiology of PV
................................................... 52
3.2
Should
ET
and PV be Considered as the Same
Disease?
..................................................................... 52
3.3
Pathophysiology and Molecular Biology of PV
............ 52
3.3.1
Overview of the Role of JAK2V617F Mutations
inPV
............................................................... 52
3.3.2
Overexpression of the PRV-1 Gene in PV
......... 53
3.3.3
Other Molecular Features Implicated in the
Pathogenesis of PV
.......................................... 53
3.3.4
Exon
12
Mutations in JAK2V6I7F Negative PV....
54
3.3.5
Single Nucleotide Polymorphisms (SNPs)
in JAK2 and EPO-R
-
Contribution of Host
Genetic Variation to CMPD Phenotype
............. 54
3.4
Cytogenetics in PV
..................................................... 54
3.5
Clinical Features and Symptoms Occurring in PV
......... 56
3.6
Disease Complications
................................................ 57
3.7
Diagnosis of Polycythemia
Vera (PV).......................... 58
3.8
Differential Diagnosis of Polycythemia
Vera................ 63
3.8.1
Absolute Polycythemia/Erythrocytosis
.............. 63
3.8.2
Relative and Spurious/Apparent Polyglobulia....
65
3.8.3
Idiopathic Erythrocytosis (IE)
........................... 66
3.9
Risk Stratification of Patients with PV
......................... 67
3.10
Treatment of PV
......................................................... 68
3.10.1
Phlebotomy
.................................................... 68
3.10.2
Antiaggregatory Therapy
................................ 68
3.10.3
Indications for Treatment and Choice
of Cytoreductive Drugs in Patients with PV
.... 69
3.10.3.1
Hydroxyurea
.................................. 70
3.10.3.2 Interferon
-α
....................................
70
3.10.3.3
Pipobroman
.................................... 70
3.10.3.4
Other Cytoreductive Agents only
Rarely Used Nowadays
................... 70
3.10.4
Allogeneic Bone Marrow Transplantation
inPV
............................................................. 71
3.10.5
Future Treatment Possibilities
-
JAK2 Inhibitors
.............................................. 71
3.11
Polycythemia
Vera
in Pregnancy
................................. 71
3.12
Childhood Polycythemias/Erythrocythosis
................... 72
3.12.1
Primary Familial and Congenital
Polycythemia
................................................. 72
3.12.2
Sporadic
Pediatric
Non-Familial PV
............... 72
3.12.3
Familial Polycythemia
Vera............................ 73
3.12.4
Congenital Secondary Erythrocytosis
.............. 73
3.12.4.1
High Affinity Hemoglobin Variants....
73
3.12.4.2
Congenital 2,3-Bisphosphoglycerate
(BPG) Deficiency
........................... 74
3.12.4.3
Polycythemias due to Abnormal
Hypoxia Sensing
............................ 74
4
Primary Myelofibrosis (PMF) [Previously
Chronic Idiopathic Myelofibrosis (CIMF),
Myelofibrosis with Myeloid Metaplasia
(МММ),
Agnogenic Myeloid Metaplasia
(AMM)l
.......................................................... 81
Lisa Pleyer, Victoria Faber, Daniel
Neureiter,
and Richard Greil
4.1
Introduction to PMF
.................................................... 82
4.2
Epidemiology of PMF
................................................. 82
4.3
Pathophysiology and Molecular Biology of PMF
......... 84
4.4
Cytogenetics in PMF
................................................... 86
4.5
Clinical Features of PMF
............................................ 86
4.6
Laboratory Findings in PMF
....................................... 88
4.6.1
Abnormal Laboratory Tests
.............................. 88
4.6.2
Blood Cell Anomalies Observed in the
Hyperproliferative Phase
.................................. 88
4.6.3
Blood Cell Anomalies Observed During
the Late-Stage Osteosclerotic Phase
.................. 89
4.7
Cytological Findings in PMF
....................................... 91
4.8
Histological Findings of Bone Marrow Biopsy
Specimen in PMF
....................................................... 91
4.9
Imaging in Patients with PMF
..................................... 91
4.10
Diagnosis of Primary Myelofibrosis
............................. 91
4.11
Differential Diagnosis for Primary Myelofibrosis
......... 93
4.12
Prognostic Scores and other Prognostic Factors
in PMF
....................................................................... 94
4.13
Treatment of Patients with Myelofibrosis
..................... 96
4.13.1
Curative Treatment Options
-
Allogeneic
Stem Cell Transplantation
............................... 99
4.13.2
Treatment of Symptomatic Myeloproliferation
as well as Constitutional Symptoms
............... 100
4.13.3
Treatment of Cytopenias in Advanced Stage
Myelofibrosis
................................................ 100
4.13.3.1
Growth Factors
............................. 100
4.13.3.2
Androgens
.................................... 100
4.13.3.3
Bisphosphonates
........................... 101
4.13.3.4
Cyclosporine A
............................ 101
4.13.4
Targeting and Modulating the Bone Marrow
Microenvironment in
PMF
............................. 101
4.13.4.1
Thalidomide
................................. 101
4.13.4.2
Thalidomide Analogues
................ 102
4.13.4.3
Targeting TNF-oc with Etanercept....
102
4.13.4.4 Interferons.................................... 102
4.13.4.5
Targeting
TGF-ß........................... 103
4.13.5
A Possible Role for Epigenetic Therapy
in PMF?
........................................................ 103
4.13.6
Tyrosine Kinase Inhibitors in PMF
................. 104
4.13.6.1
Targeting Constitutively Activated
JAK2 by Selective Tyrosine Kinase
Inhibitors
...................................... 104
4.13.6.2
Imatinib Mesylate (STI571,
Gleevec®)
.................................... 104
4.13.6.3
Farensyltransferase Inhibitors
........ 104
4.13.6.4
Other Tyrosine Kinase Inhibitors
that have been Used in PMF
......... 104
4.13.7
Indications for Splenectomy in PMF
.............. 105
4.13.8
Indications for Splenic Irradiation
.................. 106
4.13.9
Treatment of Other Foci of Extramedullary
Hematopoiesis and Their Complications
........ 106
4.13.9.1
Irradiation of Tumor-like
Manifestations of Extramedullary
Hematopoiesis
.............................. 106
4.14
Atypical Myelofibrosis Variants
.................................. 107
Contents
ix
4.14.1
Secondary Myelofibrosis, i.e., Post-Polycythemia
and Post-Essential Thrombocythemia
Myelofibrosis
................................................ 107
4.14.2
Primary Autoimmune Myelofibrosis (AIMF)
... 108
4.14.2.1
Treatment of AIMF
...................... 108
4.14.3
Familial Myelofibrosis
................................... 108
4.14.4
Idiopathic Myelofibrosis in Childhood
........... 109
5
Chronic Myeloid Leukemia (CML)
............. 117
Nikolas
von Bubnoff,
Lisa Pleyer, Daniel
Neureiter,
Victoria Faber, and Justus Duyster
5.1
Introduction
................................................................. 118
5.2
Epidemiology
.............................................................. 118
5.3
Course of Disease
........................................................ 118
5.4
Etiology and Pathogenesis of CML
.............................. 118
5.5
Classification of CML
.................................................. 120
5.6
Clinical Features and Disease Complications in CML
..... 120
5.7
Diagnosis of CML
....................................................... 121
5.7.1
Baseline Diagnostics
......................................... 122
5.7.2
Cytology of Peripheral Blood in CML
.............. 123
5.7.2.1
Changes in the Myeloid
Compartment
..................................... 123
5.7.2.2
Changes in the Lymphoid
Compartment
..................................... 123
5.7.2.3
Changes in the Platelet
Compartment
..................................... 123
5.7.2.4
Changes in the Erythroid
Compartment
..................................... 123
5.7.3
Bone Marrow Cytology in CML
........................ 123
5.7.4
Bone Marrow Histology in CML
....................... 124
5.7.5
Laboratory Findings in CML
............................. 124
5.7.6
Molecular Diagnostics in CML
.......................... 124
5.7.6.1
Conventional Cytogenetics in CML
....... 125
5.7.7
Differential Diagnosis of CML
.......................... 125
5.8
Treatment of Patients with CML
.................................. 125
5.8.1
Treatment in Chronic Phase CML
..................... 126
5.8.1.1
Hydroxyurea, Busulphan and Alpha
Interferon........................................... 126
5.8.1.2
Imatinib in the Treatment of CML
...... 126
5.8.2
Treatment of Accelerated and Blast Phase
......... 127
5.8.3
Response Criteria in CML
................................. 128
5.8.4
Monitoring Response in CML
........................... 128
5.8.5
Resistance to Imatinib in CML
.......................... 129
5.8.5.1
Definition and Incidence of
Suboptimal
Response and Treatment
Failure
............................................... 129
5.8.5.2
Mechanisms of Resistance to Imatinib
in CML
.............................................. 129
5.8.6
Novel Abl Kinase Inhibitors
.............................. 135
5.8.6.1
Preclinical Data
.................................. 135
5.8.6.2
Approved
2nd
Generation Kinase
Inhibitors in Imatinib Resistant
or Intolerant CML
.............................. 135
5.8.7
Outlook
-
Promising Strategies in Current
and Future Clinical Trials
.................................. 137
5.8.7.1
Novel Compounds in Clinical Trials
...... 137
5.8.7.2
Second Generation Abl Kinase
Inhibitors for
1st
Line Treatment
of Chronic Phase CML
....................... 140
5.8.7.3
Can Tyrosine Kinase Inhibitors Cure
CML?
................................................ 140
5.8.7.4
Immunotherapy of CML
..................... 140
5.8.8
Allogeneic Stem Cell Transplantation
................ 140
5.8.9
Prognostic Scores in CML
................................. 141
5.9
CML Variants
.............................................................. 141
5.9.1
Philadelphia Chromosome Negative CML
(Formerly Atypical CML)
................................. 141
5.9.2
CML with an Initial Thrombocythemic Phase,
CML with a Polycythemic
Prophase, CML
with
Marrow Fibrosis (Formerly Inappropriately
Termed Ph Positive
ET,
PVor PMF)
.................. 141
5.9.3
Other Ph+ Entities
............................................ 142
5.9.4
CML with Atypical Breakpoints and
an Indolent Clinical Course (Formerly
Neutrophilic CML )
........................................ 142
б
Myelodysplastic Syndromes (MDS)
........... 153
Lisa Pleyer, Daniel
Neureiter,
Victoria Faber,
and Richard Greil
6.1
Introduction
................................................................. 154
6.2
Epidemiology of MDS
................................................. 155
6.3
Pathophysiology and Molecular Biology of MDS
......... 156
6.3.1
Disturbances in Apoptosis
................................. 156
6.3.2
Alterations in
Т
-Cell
Functions and
Cytokines
......................................................... 158
6.3.3 Microenvironment
in MDS
................................ 160
6.3.4
The Role of Tumor Suppressor Genes
and Oncogenes in MDS Disease Initiation/
Perpetuation
...................................................... 160
6.3.4.1
Somatically Acquired Mutations
oftheAML-1 Gene in MDS
............... 161
6.3.4.2
OverexpressionofEVI-l in MDS
......... 161
6.3.4.3
Oncogenic Fusion Products
in MDS
.............................................. 161
6.3.4.4
Mutation of the Ras-Protooncogene
in MDS
.............................................. 162
6.3.4.5
The Role of Interferon-Regulatory
Factor-1 (IRF-l)inMDS
.................... 162
6.4
Clinical Features in MDS
............................................. 162
6.4.1
Infectious Complications in MDS
...................... 162
6.5
Laboratory Features in MDS
........................................ 166
6.6
Typical Bone Marrow Findings in MDS
....................... 167
6.7
Diagnosis and Classification of MDS
........................... 167
6.8
Prognostic and Predictive Parameters in MDS
.............. 172
6.8.1
Cytogenetics in MDS
........................................ 172
6.8.1.1
Frequency of Cytogenetic
Aberrations in MDS
........................... 172
6.8.1.2
Clinical and Prognostic Features
of Patients with Particular Cytogenetic
Aberrations in MDS
........................... 173
6.8.2
Molecular Factors Associated with Progression
of the Disease
................................................... 174
6.8.3
Prognostic Scoring Systems in MDS
.................. 175
6.8.4
Other Prognostic Markers in MDS
..................... 178
6.9
Best Supportive Care
(BSC)
of Patients with MDS
....... 178
6.9.1
Transfusion of Red Blood Cells and/or
Platelets
............................................................ 178
6.9.2
Erythropoietin
(ЕРО)
........................................ 178
6.9.3
G-CSF and Combination Treatment of
ЕРО
withG-CSF
...................................................... 179
6.9.4
Thrombopoietin (TPO) and TPO Mimetics
........ 180
6.9.4.1
PEG-rHuMGDF
................................. 181
6.9.4.2
Recombinant
Human TPO(rHuTPO)
....... 181
6.9.4.3
Romiplostim(AMG531,Nplate®)
....... 181
6.9.4.4
Oral TPO Mimetics Eltrombopag
andAKR-501
(ΎΜ477)
...................... 181
6.9.5
Other Drugs for Palliative Amelioration
of Cytopenia
..................................................... 182
Contents
6.9.6
Iron Chelation Therapy (ICT)
............................ 182
6.9.6.1
Deleterious Sequelae of Iron
Overload in MDS Patients
.................. 182
6.9.6.2
What are the Goals of ICT?
................ 183
6.9.6.3
In Whom Should ICT Be
Considered?
....................................... 183
6.9.6.4
When Should ICT Be Initiated
and for How Long?
............................ 183
6.9.6.5
Monitoring of Body Iron Stores
in MDS
.............................................. 183
6.9.6.6
Currently Available Iron Chelators
...... 184
6.10
Low-Dose Palliative Chemotherapy inMDS
............... 185
6.10.1
Low-Dose Melphalan
.................................... 185
6.10.2
Low-Dose Cytosine-arabinoside (Ara-C)
........ 185
6.11
Treatment of MDS with Curative Intention
................. 185
6.11.1
Myeloablative Chemotherapy and Allogeneic
Stem Cell Transplantation (SCT)
................... 185
6.11.2
When to Transplant in the Course
of Disease?
................................................... 186
6.11.2.1
Factors Associated with Allogeneic
SCT Outcome
................................. 187
6.11.3
Reduced Intensity Conditioning
(MC)........... 187
6.11.3.1
Patient Selection for RIC
................ 188
6.11.4
Induction of a
Т
-cell
Response Against
the Malignant Clone
...................................... 188
6.11.5
AML-like Chemotherapy in MDS
.................. 189
6.11.6
High-Dose Chemotherapy (HDCT) with
Autologous Stem Cell Rescue
........................ 189
6.12
Epigenetic Therapies: DNA-Methyltransferase
Inhibitors
................................................................... 190
6.12.1
Hypermethylation in MDS
............................. 190
6.12.2
Hypomethylating Agents
.............................. 191
6.12.2.1
S-Azacitidine (Vidaza®)
.................. 191
6.12.2.2
S-Aza^ -Deoxycy
ridine
(Decitabine)
(Dacogen®)
.................................... 192
6.12.3
Histone Deacetylase Inhibitors (HDAC-I) and
Combination Therapy with Other Epigenetic
Drugs or Differentiation Inducer
ATRA
(Vesanoid®)
................................................... 193
6.13
Immunosuppressive Treatment in MDS
...................... 193
6.13.1
Treatment with Anti-mymocyte Globulin
(ATG)
........................................................... 193
6.13.2
Immunosuppressive Treatment with
Cyciosporin A (CyA)
.................................... 194
6.13.3
Treatment of MDS Associated Autoimmune
Manifestations
............................................... 195
6.14
Targeting Bone Marrow
Microenvironment
in MDS....
195
6.14.1
Thalidomide
.................................................. 195
6.14.2
Lenalidomide (Revlimid®)
............................. 195
6.14.3
Direct Targeting of TNF-a: Infliximab and
Ethanercept
................................................... 196
6.14.4
Antiangiogenetic Therapies
........................... 197
6.15
Induction of Differentiation
-
Retinoic Acids
.............. 197
6.16
Molecular Therapies Using Kinase-Inhibitors
............. 197
6.16.1
Farensyltransferase Inhibitors (FTIs): Tipifarnib
(Zarnestra®) and Lonafarnib (Sarasar®)
......... 197
6.16.2
FUn-Antagonist Tandutinib (MLN518/
CT53518)
...................................................... 198
6.17
Targeting NF-kB
........................................................ 198
6.17.1
Bortezomib (Velcade®)
.................................. 198
6.17.2
Arsenic Trioxide (Arsenox®)
......................... 198
6.18
Modulation of Pro-Apoptotic Cytokines with
Pentoxiphylline, Dexamethasone and
Ciprofloxacine
........................................................... 199
6.19
MDS Subtypes Associated with Certain Cytogenetic
Features
..................................................................... 200
6.19.1
5q~ Syndrome
..............................................200
6.19.2
MDS with Isolated del(20q)
...........................201
6.19.3
Monosomy
7
Syndrome
.................................201
6.19.4
MDS with Isolated Trisomy
8........................201
6.19.5
17p~ Syndrome
.............................................202
6.19.6
3q21q26 Syndrome
........................................202
6.20
MDS Variants
............................................................202
6.20.1
Therapy-Related MDS
...................................202
6 20.2
Hypocellular or Hypoplastic MDS
.................205
6.20.3
Hyperfibrotic MDS
........................................205
6.20.4
Familial MDS
...............................................205
6 21
Simplified Treatment Algorithm for MDS
..................206
7
Chronic Myelomonocytic
Leukemia (CMML)
....................................... 223
Lisa Pleyer, Daniel
Neureiter,
Victoria Faber,
and Richard
Greii
7 1
Introduction to CMML
—
Problems in Classification
.....223
7.2
Epidemiology of CMML
..............................................224
7.3
Molecular Biology of CMML
......................................224
7.4
Cytogenetics of CMML
...............................................225
7 5
Clinical and Laboratory Features of CMML
.................225
7^6
Diagnosis of CMML
....................................................226
7.7
Prognostic Factors of CMML
.......................................227
7^8
Treatment of CMML
...................................................227
7.8.1
Best Supportive Care and Control of
Myeloproliferation for CMML
..........................227
7.8.2
Intensive Chemotherapy for CMML
..................228
7.8.3
Curative Treatment Options for CMML
.............228
7.8.3.1
Allogeneic Stem Cell
Transplantation
.................................. 228
7.8.3.2
Reduced Intensity Conditioning
.......... 229
7.8.4
Hypomethylating Agents in CMML
...................229
7.8.4.1
Azacitidine (Vidaza®)
......................... 229
7.8.4.2
Decitiabine (Dacogen®)
...................... 229
7.8.5
Other Treatment Options
...................................230
8
Rare Clonal Myeloid Diseases
................... 235
Thomas
Melchardt,
Lukas
Weiss, Lisa Pleyer,
Daniel
Neureiter,
Victoria Faber, and
Richard Greil
8 1
Chronic Clonal Disorders of Mast Cells
.......................236
8.1.1
Epidemiology
...................................................236
8.1.2
Course of Disease and Prognosis
.......................236
8.1.3
Pathophysiology and Molecular Biology
............236
8.1.4
Cytogenetics
.....................................................237
8.1.5
Clinical Presentation
.........................................237
8.1.6
Diagnosis and Classification of Mastocytosis
.....238
8.1.6.1
Classification of Mastocytosis
............. 238
8.1.6.2
Diagnostic Work-up of a Patient with
Suspected Mastocytosis
...................... 239
8.1.7
Differential Diagnosis
.......................................239
8.1.8
Indications for Treatment and Therapeutic
Options
.............................................................240
8.1.8.1
Treatment of Symptoms Related to
Mast Cell Degranulation
..................... 240
8.1.8.2
Treatment of Cutaneous
Mastocytosis
...................................... 241
8.1.8.3
Treatment Options in Indolent
Systemic Mastocytosis
........................ 241
8.1.8.4
Treatment of Aggressive Systemic
Mastocytosis
...................................... 241
Contents
8.2
Chronic Clonal Eosinophilic Disorders
and the Idiopathic Hypereosinophilic Syndrome
...........241
8.2.1
Idiopathic Hypereosinophilic
Syndrome (IHES)
.............................................241
8.2.1.1
Epidemiology
..................................... 242
8.2.1.2
Pathophysiology
................................. 242
8.2.1.3
Cytogenetics
...................................... 242
8.2.1.4
Clinical Presentation of IHES
(Idiopathic Hypereosinophilic
Syndrome)
......................................... 242
8.2.1.5
Diagnosis of IHES
............................. 243
8.2.1.6
Treatment
.......................................... 243
8.2.2
Clonal Eosinophilic Diseases
.............................243
8.2.2.1
Myeloid and Lymphoid Neoplasms
with Eosinophilia and Abnormalities
of PDGF-RA, PDGF-RB
orFGF-Rl
......................................... 243
8.2.2.2
Chronic Eosinophilic Leukemia
(CEL),
not Otherwise Specified
...................... 245
8.2.3
Causes of Reactive Eosinophilia
........................245
8.2.3.1
Infections as Causes of Reactive
Eosinophilia
....................................... 246
8.2.3.2
Drug-Induced Reactive
Eosinophilia
....................................... 246
8.2.3.3
Non-Malignant Diseases Associated
with Eosinophilia
............................... 246
8.2.3.4
Malignant Clonal Diseases Associated
with Eosinophilia
............................... 246
8.2.4
Acute Eosinophilic Leukemia (AEL)
.................247
8.3
Disorders of Basophilic Granulocytes
........................... 247
8.3.1
Reactive Polyclonal Basophilia
..........................247
8.3.2
Clonal Basophilia Accompanying Other
Myeloproliferative Neoplasms
...........................248
8.3.3
Acute Basophilic Leukemia
...............................248
8.4
Chronic Neutrophilic Leukemia (CNL)
.........................248
8.4.1
Differential Diagnosis of Neutrophilia
............... 249
8.5
Chronic Clonal Histiocytic Diseases
............................. 249
8.5.1
Rosai-Dorfman Syndrome (Sinus Histiocytosis
with Massive Lymphadenopathy)
.......................250
8.5.1.1
Epidemiology
..................................... 250
8.5.1.2
Clinical Features of Rosai-Dorfman
Syndrome
.......................................... 250
8.5.1.3
Diagnosis of Rosai-Dorfman
Syndrome
.......................................... 250
8.5.1.4
Histopathological Findings of
Rosai-Dorfman Syndrome
.................. 251
8.5.1.5
Treatment of Rosai-Dorfman
Syndrome
.......................................... 251
8.5.2 Langerhans
Cell Histiocytosis (LCH)
(Histiocytosis-X, eosinophilic
granuloma,
Abt-Letterer-Siewe
disease or
Hand-Schüller-Christian
disease)
......................251
8.5.2.1
Epidemiology of LCH
........................ 251
8.5.2.2
Prognosis and Course of Disease
of LCH
.............................................. 251
8.5.2.3
Clinical Presentation
.......................... 251
8.5.2.4
Diagnosis of LCH
.............................. 252
8.5.2.5
Treatment
.......................................... 253
8.5.3
Malignant Histiocytosis
.....................................253
8.5.3.1
Histiocytic Sarcoma
........................... 254
8.5.3.2
Tumors of
Langerhans
Cells
............... 254
8.5.3.3
Follicular Dendritic Cell
Sarcoma
............................................ 254
8.5.3.4
Interdigitating Dendritic Cell
Sarcoma
............................................. 254
8.5.3.5
Treatment
.......................................... 254
9
De novo
Classic Paroxysmal Nocturnal
Hemoglobinima
(PNH) (Marchiafava-Micheli
Syndrome)
.................................................. 259
Lisa Pleyer and Richard
Greii
9.1
Epidemiology of PNH
..................................................259
9.2
Pathophysiology and Molecular Biology of PNH
..........260
9.2.1
Pathomechanism of Hemolysis
.........................262
9.2.2
Pathomechanism of Hemoglobinuria and
Hemosiderinuria
................................................ 263
9.2.3
Pathomechanism of Thrombotic Tendency
.........264
9.2.4
Pathomechanism of Dystonias, Abdominal Pain
and Systemic or Pulmonary Hypertension
..........264
9.3
Functional Defects of GPI-Deficient Hematopoietic
Cells
............................................................................265
9.4
Clinical Features and Disease Complications of PNH
... 266
9.5
Diagnosis, Laboratory Findings and Diagnostic Tests
in PNH
........................................................................ 267
9.5.1
Laboratory Findings
..........................................267
9.5.2
Diagnostic Tests
................................................ 267
9.6
Differential Diagnosis of PNH
.....................................267
9.6.1
PNH Cells in Normal Individuals and After
Therapy with Campath
...................................... 268
9.7
Cytogenetics in PNH
................................................... 269
9.8
Risk Factors in PNH
....................................................269
9.9
Treatment of PNH
-
Current State of the Art
................269
9.9.1
Treatment of Anemia and Other Cytopenias in
PNH
................................................................. 270
9.9.2
Treatment of Thrombotic Events in PNH
...........270
9.9.3
Targeted Treatment
-
Complement Inhibition ....Til
9.9.3.1
Inhibition of Terminal Complement
C5 and MAC-Formation
..................... 272
9.9.3.2
Exogenous Replacement
of GPI-Linked Proteins
....................... 272
9.9.4
Immunosuppression
..........................................273
9.9.5
Allogeneic Stem Cell Transplantation
for PNH
............................................................ 273
9.9.6 Perioperative
Management of PNH Patients
........274
9.9.7
Avoidance of Drugs Known to Induce
Hemolytic Anemia
............................................274
9.9.8
Management of Pregnancy in Women
with PNH
.........................................................274
10
Clonal Bone Marrow Failure Overlap
Syndromes
................................................ 281
Lisa Pleyer, Daniel
Neureiter,
and Richard Greil
10.1
Introduction
............................................................... 281
10.2
MDS/PNH Overlap Syndromes
.................................. 282
10.3
Aplastic Anemia (AA) and AA Overlap Syndromes....
283
10.3.1
Aplastic Anemia
............................................283
10.3.2
AA/PNH Overlap Syndromes
........................283
10.3.3
AA/MDS Overlap Syndromes
........................284
10.4
Т
-cell
Large Granular Lymphocyte Leukemia
(T-LGL) and T-LGL Overlap Syndromes
....................285
10.4.1
T-LGL
..........................................................285
10.4.2
T-LGL/MDS Overlap Syndromes
...................286
10.4.3
T-LGL/PNH Overlap Syndromes
...................286
10.4.4
T-LGL/AA and T-LGL/Pure Red Cell
Aplasia
(PRCA)
Overlap Syndromes
..........................286
List of Contributors
............................................. 289
About the Editors
................................................ 291
R.
Greii
·
L.
Pleyer
D.
Neureiter
-V.
Faber
Eds.
Chronic Myeloid Neoplasias
and Clonai Overlap Syndromes
Epidemiology, Pathophysiology
and Treatment
Options
This book comprises an in-depth view on the current knowledge of chronic
donai
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
leukémiás,
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.
|
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| indexdate | 2024-07-09T21:34:14Z |
| institution | BVB |
| isbn | 9783211798911 |
| language | English |
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| physical | XI, 292 S. Ill., graph. Darst. |
| publishDate | 2010 |
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| spelling | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options Richard Greil ... ed. Wien [u.a.] Springer 2010 XI, 292 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Myelose (DE-588)4170926-3 gnd rswk-swf Myelose (DE-588)4170926-3 s DE-604 Greil, Richard 1957- Sonstige (DE-588)133878546 oth Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017315188&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017315188&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options Myelose (DE-588)4170926-3 gnd |
| subject_GND | (DE-588)4170926-3 |
| title | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options |
| title_auth | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options |
| title_exact_search | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options |
| title_full | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options Richard Greil ... ed. |
| title_fullStr | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options Richard Greil ... ed. |
| title_full_unstemmed | Chronic myeloid neoplasias and clonal overlap syndromes epidemiology, pathophysiology and treatment options Richard Greil ... ed. |
| title_short | Chronic myeloid neoplasias and clonal overlap syndromes |
| title_sort | chronic myeloid neoplasias and clonal overlap syndromes epidemiology pathophysiology and treatment options |
| title_sub | epidemiology, pathophysiology and treatment options |
| topic | Myelose (DE-588)4170926-3 gnd |
| topic_facet | Myelose |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017315188&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017315188&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
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