Myeloproliferative Neoplasms (Exam III) Flashcards
(67 cards)
1
Q
definition of myeloproliferative neoplasm
A
Greoup of disorders that are considered clonal malignancies of the hematopoietic stem cell
2
Q
Myeloproliferative neoplasm usually affects
A
Usually >40 years old
3
Q
Myeloproliferative neoplasm
results in
A
- BM hyperplasia and Splenomegaly or Hepatosplenomegaly
- Dominant expression of one or more “myeloid “ cell lines
- Overproduction of one or more of the PB formed elements
4
Q
Chronic Myeloid Leukemia (CML)
A
granulocytes
5
Q
Chronic Neutrophilic leukemia
A
neutrophils
6
Q
Chronic eosinophil (CEL) not otheriwise specified
A
eosinophils
7
Q
Polycythemia vera (PV)
A
Pancytosis
8
Q
Essential Thrombocytopenia (ET)
A
Megakaryocytes/PLT
9
Q
Primary Myelofibrosis (PMF)
A
Fibrosos
10
Q
Myeloproliferative neoplasm
Transitions
A
Have frequent transitions and many overlapping characteristics between diseases
11
Q
Chronic Myeloid Leukemia
A
BCR-ABL1+
12
Q
definition of CML
A
Chronic myeloproliferative disorder with an increase in granulocytes in peripheral blood and marked granulocytic hyperplasia in bone marrow
- PB includs: neutrophils with immature forms, eosinophils and basophils granulocytes
13
Q
CML also called
A
- Chronic Myelogenous/ Myelocytic Leukemia
- Chronic Granulocytic Leukemia
14
Q
1st human disease traced to a chromosomal abnormality
CML
A
Philadelphia chromosome
- identified in 90-95% of patients with CML
- Not diagnostic, also found in 5% of children and 20% of adults with ALL and 2% of patients with AML
15
Q
CML pathogenesis
A
philadelphia chromosome
- Chromosome 22q- (shortened chromosome 22)
t(9;22)
increases proliferation and inhibits apoptosis
16
Q
BCR-ABL+ gene produces
A
p210-tyrosine kinase
17
Q
p210-kinase causes
A
- activation of several signaling pathways
- caused increased proliferative capacity
- leads to slightly delayed maturation and lacks responsiveness to normal growth regulators
- Prevents apoptosis (cell death) in leukemia cells
- Considered essential in the pathogenesis of CML
18
Q
Atypical CML
A
those who don’t have BCR-ABL gene
- Different prognosis and treatment
19
Q
Not all Philadelphia chrom. or BCR-ABL genes are identical
A
- fusion protein can result in different sizes, different outcomes and different classification
- Treatment has to be determined by individual case
20
Q
CML clinical features
A
Can be asymptomatic or symptomatic
- common to be discovered incidentally
21
Q
typical CML symptoms
A
- Malaise/fatigue = anemia
- Abdomen Fullness
- Loss of Apetite = splenomegaly
- Night sweats
- Weight Loss
- Bone tenderness/aching
22
Q
CML phases can be
A
biphasic or triphasic
23
Q
Chronic CML phase
A
- Usually diagnosed in this phase
- Disease remains stable for several years
- Responsive to chemo
24
Q
Accelerated phase CML
A
3-5 years after onset (untreated)
Worsening clinical symptoms
- Unexplained fevers
- Significant weight loss
- Worsening Splenomegaly
- Bleeding
- Thrombosis
- Infections
25
Blast phase CML (Blast cell crisis)
Conversion of CML to aggressive form of acute leukemia that is difficult to treat
26
Chronic CML phase CBC
Increased WBC count (<100,000 microL) - **Leukocytosis**
Decreased Hemoglobin and Hematocrit
- anemia
- Severity is proportional to the degree of leukocytosis
Possible Thrombocytosis (EXAM) **TRUE**
27
CML **lab findings** Chronic Phase
Increased WBC - Leukocytosis
Increased Neutrophils with immature forms
- May resemble "shift left", but not due to BM response to infection
- see all stages from occasional myeloblast (>2%) to segmented neutrophils
- Usually more myelocytes than metamyelocytes --> "Myelocyte Bulge"
Increased Eosinophil and Basophils
- **Basophilia - one of the first indicators (>2% in chronic phase)**
Possible increased PLT thrombocytosis
Normocytic, Normochromic Anemia (Low RBC)
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CML Chronic phase
**Additional findings**
- giant platelets
- nRBCs
- Anisocytosis
- Basophilic stippling
- polychromasia
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CML Chronic Phase BM
Hypercellular
- marked granulocytic hyperplasia
Blasts not significantly increased (<5%)
Increased Neutrophilic, Basophilic, Eosinophilic cells
Increased Megakaryocytes
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BM - CML accelerated
- blasts increasing 5-19%
- Megkaryocyte clusters
- Fibrosis
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PB - CML accelerated
- increasing blasts and promyelocytes
- **basophils** more or equal to 20%
- Thrombocytopenia
Worsening splenomegaly, bone pain, anemia
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CML blast phase
BM
- **Blasts, more or equal to 20% and in clusters**
- increased fibrosis
- dysplastic features
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CML blast phase
PB
**Blasts >20%**
**conversion to Acute Leukemia**
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Cytogenetics CML
Detection of t(9;22)(q34;q11)(BCR-ABL+)
performed by:
- FISH = Fluorescnece in Situ Hybridization
- RT-PCR = reverse transcriptase polymerase chain reaction
35
RT-PCR
- extremely sensitive
- Used to detect residual disease or recurrence after treatment
36
CML - LAP
LOW LAP score
Stains leukoyte alkaline phosphatase activity in granules
- present in normal neutrophilic granules
- decreased/absent in malignant neutrophilic granules
-
Returns to normal or increased due to
- remission of disease with therapy
- infection
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Toxic vacuoles
Leukomoid RXN: Increased
CML: Absent
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Toxic granulation
Leukomoid RXN: Increased
CML: Absent
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Dohle Bodies
Leukomoid RXN: Increased
CML: Absent
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Eosinophilia
Leukomoid RXN: Normal
CML: Increased
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Basophilia
Leukomoid RXN: normal
CML: increased
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Myelocyte bulge
Leukomoid RXN: absent
CML: present
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LAP score
Leukomoid RXN: high
CML: low
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Ph Chromosome
Leukomoid RXN: negative
CML: positive
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CML prognosis
Medial survival 4-6 years
Poor prognostic indicators predicting blast transformation
- Additional chromosomes abnormalities
- Severe hepatosplenomegaky
- Change in PLT count - Thrombocytosis to Thrombocytopenia
- Extreme leukocytosis >100,000 uL
- BM blasts >5%
- PB basophils >20%
- Tumor suppressor gene p53 - may induce drug resistance
46
CML treatment
Myelosuppressive treatments (cytotoxic therapy)
Tyrosine Kinase Inhibitor
Allogenic bone marrow transplant
47
Treatment for CML
Myelosuppressive treatments (Cytotoxic therapy)
- hydroxyurea, interferon-alpha, or busulfan tehrapy
Targeted to controlling hyperproliferation of myeloid elements by inhibiting cell division
48
Allogenic bone marrow transplant
CML treatment
ONLY PROVEN CURE
Transplant related mortality and Graft vs. Host disease
- worse in older patients
- have to consider risks associated
49
Tyrosine kinase inhibitor
CML treatment
Imatinib mesylate (Gleevec)
- inhibits proliferation, slows skin cell growht, and induces cell death
- first drug developed against a specific molecular target
- Treats all phases of CML
50
Chronic Neutrophilic Leukemia (CNL)
PB
major criteria: WBC count >25,000/uL
and
>80% band or segmented neutrophils
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CNL most cases
mutation CSF3R
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CNL characteristics
**Basophilia and Eosinophilia NOT present**
**Does NOT have philadelphia chromosome**
**LAP increased**
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Chronic Eosinophilic leukemia (CEL)
clonal expansion of eosinophil precusors
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major criteria CEL
**PB** eosinophils >1,500 microL
(normal range: 0-500 microL)
**Does not have Ph Chromosome**
Tissue damage occurs from eosinophilic granules
55
Polycythemia Vera Definition (PV)
Chronic abnormaility of the hematopoietic stem cell characterized by uncontrolled proliferation of
- **erythroid cells**
- granulocytic cells (neutrophils)
- Megakaryocytic cells
56
Etiology PV
current theory:
JAK2 V617F mutation, allowing for RBC production independent of erythropoietin (found in 90-95% cases)
57
PV clinical features
Chronic disease with insidious onset (asymptomatic/routine doctor visit)
possible symptoms
- Thrombosis/bleeding
- Splenomegaly and/or hepatomegaly
- hyper viscosity
- Hypertension
- Gout
58
PV CBC + Peripheral smear
**Pancytosis**
- Increased RBC count, Hgb, Hct
- Increased PLT count (thrombocytosis) - abnormal morphology/fxn
- Increased relative and absolute Granulocytosis - mostly enutrophils, but can see increase in Eosinophil and Basophils
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PV - BM findings
Hypercellularity with Pancytosis
- erythroid, Myeloid, Megakaryoctic Hyperplasia
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Secondary Polycythemia
Increased production of RBCs due to response to other factors
- hypoxia
- Erythropoeietin (EPO) producing tumor
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Relative Polycythemia
Increased RBC count due to decreased plasma volume
- dehydration/burns
AKA tertiary polycythemia
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Differential diagnosis
Secondary polycythemia
secondary: RBCs only
PV: multiple cell lines
63
EPO
(secondary vs PV)
Secondary: increased
PV: decreased
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Relative vs PV increased cells
Relative: RBCs only
PV: multiple lines
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PV treatment
Therapeutic phlebotomy
- want to create a frequency (1 unit/weekly) to bring hematocrit below:
1. men <45%
2. Women <40%
other options:
- Myelosuprressive therapy
- radioactive phosphoruous (UV radiation absorbed into the BM)
66
Essentiak Thrombocythemia (ET) - definition
Chronic myeloproliferative disorder characteristics by **marked thrombocytosis** associated with **abnormal platelet function** and an increased **risk of thrombosis and hemorrhage**
67
Common mutations in ET
