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Clinical Pathology > Theme 7 Haematology: CMPD and CML > Flashcards

Theme 7 Haematology: CMPD and CML Flashcards

1
Q

What is CMPD?

A
  • chronic myeloproliferative disorders
  • clonal stem cell disorders of the bone marrow
  • malignant –> propagated by an abnormality in the pre cursor progenitor cell in the bone marrow
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2
Q

What are the 3 types of CMPD?

A
  1. Polycythaemia vera (PV)
  2. Essential thrombocytosis (ET)
  3. Idiopathic myelofibrosis (IMF)
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3
Q

What is polycythaemia vera and why does it occur?

A
  • increased red cells (+/- neutrophils/ platelet)

- bone marrow is making too many red cells due to a mutation in JAK2

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4
Q

What is essential thrombocytosis (ET)?

A

-increased platelets

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5
Q

What is idiopathic myelofibrosis (IMF)?

A

variable cytopenias with a large spleen

distinguish from other causes of splenomegaly

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6
Q

For polycythaemia vera, what is?:

  1. Age distribution
  2. Symptoms
  3. Signs
A
  1. Age distribution: all ages, peak at 50-70 yrs
  2. Symptoms: insidious, itching, plethoric (red) face, headache, muzziness, general malaise, tinnitus, peptic ulcer, gout, gangrene of toes
  3. Signs: plethora, engorged retinal veins, splenomegaly
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7
Q

How do we diagnose PV?

A
  • persistent increased Hb/hct > 0.5

- if haematocrit is above 50% on two different occasions

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8
Q

What is haematocrit?

A

ratio of volume of red cells to total volume of blood

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9
Q

What are the two different ways to classify PV?

A
  1. Relative or absolute polycythaemia

2. Primary or secondary polycythaemia

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10
Q

What is the cause of primary polycythaemia

A

polycythaemia vera

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11
Q

What are some causes of secondary polycythaemia?

A
  • central hypoxic process - chronic lung disease, smoker
  • renal disease
  • EPO producing tumours
  • drug associated
  • idiopathic erythrocytosis
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12
Q

If the EPO is normal or low, does the patient have primary or secondary PV ?

A

Primary

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13
Q

Which mutation in peripheral blood DNA is diagnostic of a myeloproliferative disorder?

A

JAK2 V617F

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14
Q

How does JAK2 mutation cause CMPD?

A

Receptor for EPO is permanently switched off with JAK2 mutation
EPO doesn’t need to bind the cell just keeps multiplying

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15
Q

How do you treat PV?

A
  • take away a pint of blood to lower haematocrit
  • aspirin 75mg daily to reduce risk of thrombosis
  • treatment to prevent clots
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16
Q

What are the two types of thrombocytosis?

A
  1. Primary essential thrombocytosis (ET) –> bone marrow is making too many platelets leaving at risk of thrombosis (platelet > 450 x 10^9)
  2. Reactive thrombocytosis
17
Q

What are the causes of reactive thrombocytosis?

A
  • surgery
  • infection
  • inflammation
  • malignancy
  • iron deficiency
  • hyposplenism
  • haemolysis
  • drug induced (steroids, adrenaline)
  • rebound post chemo
18
Q

What are the 1st line investigations for thrombocytosis?

A
  • FBC and film
  • ferritin
  • CRP
  • CXR
  • ESR
19
Q

What are the 2nd line investigations for thrombocytosis?

A
  • JAK2
  • CALR
  • bone marrow biopsy?
  • search for secondary cause
20
Q

Other than the JAK2 mutation, what is the other mutation that can increase risk of ET?

A

CALR

Calreticulin mutation

21
Q

How do we treat ET?

A
  1. Assess thrombotic risk based on:
    - age
    - hypertension
    - diabetes
    - platelet count > 1500
    - history of thrombosis
  2. Antiplatelet treatment - aspirin 75 mg daily
  3. Cytoreduction - only if one or more risk factor
22
Q

What is cytoreduction?

A

Impair the bone marrows ability to make cells to reduce platelet count to a normal level

23
Q

Which drug is an anti-folate drug that inhibits the bone marrows ability to make platelets?

A

hydroxycarbamide (used for cytoreduction in ET)

24
Q

What is the presentation of myelofibrosis?

A
  • pancytopenia –> low red cells, white cells and platelets
  • drenchy night sweats, persistant fever and more than 10% weight loss
  • massive splenomegaly as spleen takes over making RBCs, WBCs and platelets
25
Q

How to we diagnose myelofibrosis?

A
  • blood film
  • bone marrow
  • JAK2 mutation in 50%
  • CALR mutation in 30%
26
Q

What are the causes of splenomegaly? (acronym: CHICAGO)

A

-Cancer
-Haematological - myelofibrosis, CML, CLL, hairy cell leukaemia
-Infection - schistosomiasis, malaria
-Congestion - liver disease
-Autoimmune - haemolysis, SLE
-Glycogen storage disorder
Other - amyloid, sarcoid

27
Q

In splenomegaly, what is:

  1. Treatment
  2. Prognosis
A
  1. Supportive care, JAK2 inhibitors, bone marrow transplant

2. Poor, median survival = 5 years

28
Q

Who gets chronic myeloid leukaemia?

A
  • median age at diagnosis: 55-60 years

- 5x more common in female

29
Q

What are the haematological characteristics of CML?

A
  • leucocytosis –> very high white cell count
  • leucoerythroblastic blood picture
  • anaemia
  • splenomegaly
30
Q

What are the symptoms of CML?

A
  • abdominal discomfort
  • abdominal pain
  • fatigue
  • venous occlusion
  • gout
  • splenomegaly
  • splenic infection
  • anaemia
  • retinal vein, DVT, priapism
  • hyperuricaemia
31
Q

What is meant by the 9:22 chromosome translocation?

A
  • parts of chromosome 9 and 22 can fuse together to make an oncogene
  • this is known as the “philadelphia chromosome” in CML
32
Q

What is Gleevec?

A
  • a small molecule specifically designed to block the active site in the BCR-ACL tyrosine kinase to inhibit tyrosine kinase
  • a.k.a imatibin
  • revolutional treatment for CML with good survival
  • however resistance is a problem
33
Q

How do we treat CML?

A

Chronic:
-with TKIs

Acute leukaemic transformation/blast crisis:
-intensive chemotherapy, TKI and bone marrow transplant

34
Q

What is CML?

A
  • pluripotent stem cell disorder
  • defined by the t(9;22) translocation
  • driven by BCR-ABL fusion tyrosine kinase
  • chronic phase followed by acute transformation
  • imatinib has proved highly successful
  • BCR-ABL mutations confer resistance to imatibin

Clinical Pathology (57 decks)

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