84 Essential Thrombocythemia

Question 1

TRUE OR FALSE

The annual incidence of ET is approximately 2 per 100,000 population and appears slightly more common in females.

Answer 1

TRUE

The annual incidence of ET is approximately 2 per 100,000 population and appears slightly more common in females.

Question 2

Mutation present in the majority of JAK2/MPL–wild-type patients

Answer 2

Calreticulin gene (CALR)

Question 3

A JAK2V617F mutation is found in approximately _____ of patients with ET.

Answer 3

50%

Acquired mutations in C-MPL are found in 4% of ET patients

Question 4

A key endoplasmic reticulum protein with calcium-buffering and protein chaperone activity

Answer 4

Calreticulin

Question 5

Approximately ____% of ET patients have a mild degree of palpable splenomegaly at diagnosis

Answer 5

10%

Question 6

Major source of morbidity and mortality in ET

Answer 6

Thrombosis

Question 7

A distinct clinicopathologic syndrome caused by occlusion of small blood vessels, manifests as discomfort and burning sensations in the fingers or toes, sometimes accompanied by mottling or discoloration of the skin.

Answer 7

Erythromelalgia

Question 8

The strongest predictive factors for thrombotic complications

Answer 8

Age greater than 60 years
A history of previous thrombosis

Question 9

Poor predictors of thrombotic risk

Answer 9

Platelet count and leucocyte count

Question 10

The presence of this mutation is associated with a lesser risk of thrombosis or disease progression.

Answer 10

CALR

Question 11

TRUE OR FALSE

Serious bleeding is less common than thrombosis and mainly affects the nasal and buccal mucosa and the gastrointestinal tract, although central nervous system hemorrhage may occur.

Answer 11

TRUE

Serious bleeding is less common than thrombosis and mainly affects the nasal and buccal mucosa and the gastrointestinal tract, although central nervous system hemorrhage may occur.

Question 12

Laboratory investigation of thrombocytosis

two tests taken at least 3 months apart

Answer 12

• Medical History
• CRP/ESR
• MCV/Ferritin

Question 13

Diagnostic Criteria for Essential
Thrombocythemia

Answer 13

• A1 Sustained platelet count >450 × 109/L
• A2 Presence of an acquired pathogenic mutation (eg, in JAK2,CALR, or MPL)
• A3 No other myeloid malignancy, especially polycythemia vera, primary myelofibrosis, chronic myeloid leukemia, or myelodysplastic syndrome
• A4 No reactive cause for thrombocytosis and normal iron stores
• A5 Marrow studies showing increased megakaryocytes displaying a spectrum of morphology with prominent large hyperlobulated forms; reticulin is generally not increased

Diagnosis requires A1 to A3 or A1 + A3 to A5

Question 14

Causes of Spurious Thrombocytosis

Answer 14

• Cryoglobulinemia
• Cytoplasmic fragmentation in acute leukemia
• Red cell fragmentation
• Bacteremia

Question 15

TRUE OR FALSE

The neutrophil count may be slightly to mildly elevated but is usually not above 20 × 109/L.

Answer 15

TRUE

The neutrophil count may be slightly to mildly elevated but is usually not above 20 × 109/L.

Question 16

Levels of thrombopoietin are (decrease, normal or elevated) in ET and have no diagnostic utility.

Answer 16

Normal or slightly elevated

Question 17

In the absence of marrow cytogenetic analysis, molecular testing for the ___________ is also recommended

Answer 17

BCR-ABL1 fusion gene

to exclude CML

Question 18

The marrow aspirate in ET often shows

Answer 18

Large, hyperlobulated megakaryocytes

Question 19

Mutation that shows hypocellular marrow in BMA

Answer 19

C-MPL

Question 20

A secondary increase in platelet count, initiated by cytokines such as _________

Answer 20

Interleukin-6

Question 21

Familial thrombocytosis is a rare disorder caused by mutations in ____________, _____________ or other unknown genes.

Answer 21

THPO (thrombopoietin gene)
C-MPL

Question 22

Characteristics of patients with CML present with an isolated thrombocytosis

Answer 22

• Often female
• With absent or minimal splenomegaly
• A normal or marginally elevated white cell count
• Usually without basophilia or circulating myeloid progenitors.
• Small hypolobulated megakaryocytes typical of CML

Question 23

TRUE OR FALSE

Suspected cases of ET that are negative for a relevant somatic mutation undergo molecular analysis of blood for the BCR-ABL1 fusion gene.

Answer 23

TRUE

Suspected cases of ET that are negative for a relevant somatic mutation undergo molecular analysis of blood for the BCR-ABL1 fusion gene.

Question 24

MDS with associated thrombocytosis

Answer 24

Isolated deletion of chromosome 5q (“5q-minus syndrome”)

Refractory anemia, with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T)

Approximately half of patients with MDS/MPN-RS-T harbor a JAK2V617F mutation or, rarely, a mutation in C-MPL.

Question 25

TRUE OR FALSE

Karyotypic abnormalities are present in up to 50% of ET patients compared with only approximately 5% of patients with PMF, indicating a greater degree of genetic instability.

Answer 25

FALSE

Karyotypic abnormalities are present in up to 50% of myelofibrosis patients compared with only approximately 5% of patients with ET, indicating a greater degree of genetic instability.

Question 26

TRUE OR FALSE

In contrast to de novo AML, balanced chromosomal translocations are rare in post-MPN AML.

Answer 26

TRUE

In contrast to de novo AML, balanced chromosomal translocations are rare in post-MPN AML.

Question 27

Drug that is recommended for nearly all ET patients unless contraindicated and is possibly not needed in patients with the lowest risk profile (eg, patients with CALR mutations and no other risk factors)

Answer 27

Aspirin

Question 28

Risk Stratification for Patients with Essential Thrombocythemia

Answer 28

High Risk:
* Age >60 years
* Prior thrombosis
* Platelets >1500 × 109/L

Intermediate Risk:
* Age 40–60 years

Low Risk:
* Age <40 years

Question 29

Drug used as first-line therapy for patients requiring treatment, and is the only cytoreductive agent proven to reduce thrombotic events

Answer 29

Hydroxyurea

Question 30

Major complications of Hydroxyurea

Answer 30

Reversible myelosuppression
Ulceration of the buccal mucosa or lower leg

Question 31

Drugs only recommended in patients older than 75 years of age

Answer 31

Pipobroman
Busulfan
Radioactive Phosphorus

Question 32

A quinazoline derivative, reduces the platelet count by inhibition of megakaryocyte differentiation

Answer 32

Anagrelide

Question 33

Side effects of Anagrelide

Answer 33

• palpitations
• fluid retention
• heart failure
• headaches
• Associated with an increase in marrow reticulin over time

• Result from its vasodilatory and positive inotropic actions
• Caution in older adult patients or those with preexisting cardiac disease.

Question 34

Clinical trial showing nonsuperiority of Anagrelide to HU

Answer 34

ANAHYDRET Trial

Question 35

Because this agent is free from leukemogenic or teratogenic effects, it is often used for younger patients or during conception and pregnancy.

Answer 35

Recombinant interferon-α

Pegylated interferon-α, for which less frequent administration is required, may be more convenient but the side effect profile appears similar to the native compound.

Question 36

Drugs thar are effective at controlling the platelet count but are associated with an increased risk of progression to acute leukemia, particularly when used sequentially with hydroxyurea

Answer 36

Radioactive (32P) phosphorus

Alkylating agents such as busulfan

Both 32P and busulfan can be given intermittently, with long intervals between doses, and may be useful in treating older patients who are unable to visit the clinic on a regular basis.

Question 37

Treatment for each type of ET

Very-low-risk:
Low-risk:
Intermediate-risk:
High-risk:

Answer 37

Very-low-risk: observation alone or, at most, Low-dose:aspirin therapy
Low-risk: once- or twice-per-day aspirin
Intermediate-risk: aspirin and hydroxyurea
High-risk: hydroxyurea and either twice-daily aspirin (arterial thrombosis) or hydroxyurea and systemic anticoagulation (eg, low-dose heparin or a direct thrombin inhibitor)

Question 38

The three risk factors for classification of ET

Answer 38

History of thrombosis
Age greater than 60 years
Presence of either a JAK2 or C-MPL mutation

Question 39

Thromboprophylaxis appears to be safe during pregnancy (eg, with low doses of low-molecular-weight heparin) and may be considered for patients with a history of thrombosis or pregnancy loss; in those with prior thrombosis, treatment should be continued for _______________postpartum

Answer 39

6 weeks

Question 40

Factors independently associated with decreased overall survival in ET

Answer 40

History of prior thrombosis
Anemia
Leukocytosis

Additional factors with an increased risk of thrombosis:
* Predisposition to atherosclerotic diseases (diabetes, hypertension, hypercholesterolemia, or tobacco use)
* Presence of a JAK2V617F or C-MPL mutation or increased marrow fibrosis at diagnosis

Question 41

Obstetric complications in ET are more prominent in those with_______________disease

Answer 41

JAK2V617F-positive

Question 42

The agent of choice for patients with high-risk disease should cytoreductive therapy be required during pregnancy

Answer 42

Interferon-α

Question 43

TRUE OR FALSE

Incidental (eg, traumatic) or elective splenectomy in ET patients generally results in an increase in the platelet count and also an increase in thrombotic and hemorrhagic complications, so should be avoided if at all possible.

Answer 43

TRUE

Incidental (eg, traumatic) or elective splenectomy in ET patients generally results in an increase in the platelet count and also an increase in thrombotic and hemorrhagic complications, so should be avoided if at all possible.

Question 44

Considered to mandate cytoreductive therapy in ET patients

Answer 44

Age older than 60 years or
History of previous thrombosis