Haematology 10: CML and myeloproliferative disorders Flashcards

1
Q

What are MPNs?

A

Myeloproliferative neoplasms:

A myeloproliferative disorder that lead to an excess of differentiated myeloid cells (platelets, RBCs and leukocytes)

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2
Q

What are some examples of MPNs? mutation / what proportion?

A

Essential Thrombocythaemia - JAK2 (55%)

Polycythaemia Vera - JAK2 (95%)

Myelofibrosis - JAK2 (50%)

CML (classesd as an MPN)

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3
Q

What is essential thrombocythaemia? cause?

A

Megakaryocytes are making too many platelets leads to a v. high platelet count (>450 consistently)

JAK2 mutation in 55%

No evidence of other cause

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4
Q

What is the mx of essential thrombocythaemia?

A

Aspirin to reduce stroke risk

Hydroxycarbamide to lower count

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5
Q

What is polycythaemia (ruba) vera

A

Excess RBC production -> Haematocrit >0.52 / 0.48 (M / F), Often thrombocythaemia as well

Hyperviscosity, hypervolaemia, hypermetabolism -> Headaches, light-headedness, visual disturbance, fatigue, dyspnoea

High risk of thrombotic events e.g. MI, Stroke, Budd-Chiari (portal vein thrombosis)

95% association w/ JAK2

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6
Q

What is the mx of polycythaemia vera?

A

Aspirin to reduce stroke risk

Venesection (taking blood to lower haematocrit)

Hydroxycarbamide to lower count

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7
Q

How does myelofibrosis occur?

A

Clonal proliferation of stem cells in the bone marrow

This results in cytokine release and fibrosis of the bone marrow

As a result, there is reduced production of all cell lineages (this is different to the other ones as they have increased production)

NB: Polycythaemia vera and essential thrombocythaemia can both progress to this

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8
Q

What are the features of myelofibrosis?

A

JAK2 mutation present in 50%

Pancytopenia

Splenomegaly (can be massive splenomegaly) - as seen in Exam Qs

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9
Q

What else can classically present with massive splenomegaly in exam Qs?

A

CML
Myelofibrosis
Leishmanasis

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10
Q

Mx of myelofibrosis?

A

Stem cell transplant likely only cure - if early and before BM has fibrosed

Ruloxitnib - JAK inhibitor

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11
Q

What are the different types of polycythaemia vera?

A

Primary - familial / PV

Secondary - Disease, high altitude, chronic hypoxia

Pseudo - reduced plasma volume, dehydration

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12
Q

Difference between early and late myelofibrosis?

A

Prefibrotic -> mild changes, isolated thrombocytosis

Fibrotic -> splenomegaly, blood changes, dry tap (BUZZWORD), prominent collagen fibrosis in histological section, osteoscleoris

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13
Q

Typical presentation of CML?

A
  • Typically onset age 35-55 in EMQs
  • LUQ pain - Splenomegaly
  • Mostly asymptomatic if diagnosed in chronic phase

May present with symptoms of acute leukaemia if in accelerated / blast phase (~10%) - not seen as much these days

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14
Q

CML blood test results?

A

WCC - V. high (can include all different stages - myelocytes to neutrophils)
Hb normal or low
Plt - high initially but can drop later in disease

Basophils - Raised (caused by few conditions)
Monocytes - Should be low (if its high indicates CMML)

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15
Q

Blood film of CML?

A
  • “Left shift”
  • Leukocytosis
  • Eosinophilia
  • Basophilia

Hypoloblated megakaryocytes

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16
Q

What is the genetic cause of CML and how is this detected?

A

Nearly all CML is associated w/ philadelphia chromosome

BCR-ABL1 fusion gene due to t(9;22) and formation of Philadelphia chromosome

This is detected by FISH (Fluorescence in situ hybridization) studies

17
Q

What are the different phases of CML?

A

Chronic (85-90%)

Accelerated (median 6-12m):
Increasing number of blasts in BM (>10%)
Lack of response to therapy
Additional abnormalities in addition to BCR-ABL1

Blast crisis (median survival 3-6m):
>20% blasts in bone marrow (FLAWS for months)
Behaves like an acute leukaemia

18
Q

How to differ between CML in blast crisis v AML?

A

Ph Chr BCR-ABL present in all CML

Hx of CML

CML neutrophilia + L shift + basophilia

19
Q

What is the Mx of CML? prognosis?

A

Tyrosine Kinase Inhibitors
1st Generation: Imatinib (MAIN ONE)
2nd Generation: Dasatinib, Nilotinib, Bosutinib
3rd Generation: Ponatinib

> 90% 10y survival -> Small percentage of patients will fail treatment and need transplants

20
Q

Which of the following mutations is diagnostic for polycythaemia rubra vera?

Calreticulin
JAK2 V617F
MPL
CFTR F508
TP53
A

JAK2 V617F

21
Q

Which of the following is used to manage CML?

Ibrutinib
Imatinib
ABVD
Brentuximab vedotin
CAR-T cell therapy
A

Imatinib - (BCR-ABL) Tyrosine Kinase inhibitor

22
Q

Which of the following translocations is responsible for the Philadelphia chromosome?

t(15;17)
t(8;14)
t(11;14)
t(14;18)
t(9;22)
A

E - t(9;22) = CML

A: PML-RARA fusion oncogene in acute promyelocytic leukaemia (APML); aggressive form a/w DIC; rx ATRA
B: c-Myc oncogene
C: cyclin D1 (mantle cell)
D: bcl-2 (follicular)

23
Q

What MPN might show dry tap (inc reticulin / collagen fibrosis) on BM?

A

Myelofibrosis

24
Q

What MPN might show teardrop poikilocytes and leukrythroblasts and giant plts?

A

Myelofibrosis