Myeloproliferative Neoplasms

Question 1

What are MPNs

Answer 1

Clonal, hsc diseases that result in excessive and uncontrollable production of cells in one or more cell lineages.

Question 2

What is seen in mpns typically

Answer 2

Hyperviscosity and organomegaly

Question 3

Blue book ?

Answer 3

Song

Question 4

What is the PEP and JMC

Answer 4

P-polycythemia Vera
E-Essential throbocythemia
P- Primary myelofibrosis

JMC -JAK2/MPL/CALR mutation

Question 5

What is polycythemia vera

Answer 5

A myeloproliferative neoplasm characterised by an absolute increase in red cell mass above the higher interval of normal, with associated thrombocytosis and leukocytosis

Question 6

Prognosis of PV

Answer 6

Untreated -6-18 months
Treatment with phlebotomy- 3-5 years or 3.5
Treatment with immunosuppression-7-12years

Question 7

Is PV primary or secondary?…
Why?

Answer 7

Yes
Because it is characterised by an increased sensitivity of erythroid progenitors to growth factors without an increase in the level or production of growth factors
Thus referred to as growth factor independent erythroid hyperplasia

Question 8

Symptoms of PV

Answer 8

P -pruritus, progressive weight loss,paresthesia
O
L
Y
C conjunctival plethora, constitutional symptoms
Y
T
H
E erythromelalgia, excessive sweating
M
I
A

V vertigo, visual disturbances
E
R
A

Question 9

Bleeding and thrombotic events

Answer 9

2-10% die due to hemorrhage
Bleeding typically due to acquired causes like acquired platete or vwf defects

Thrombotic events:66%arterial, 36%venous
Unusual sites
Coronary events

Question 10

Diagnosis of PV

Answer 10

2 major+1 minor
Or
All 3 major.

Question 11

Major and minor criteria for PV

Answer 11

Hb>16.5g/dl for males, 16 for females
Hct of 49% for males, 48% for females or >25% increase in red cell mass above normal level
Trilineage hyperplasia or panmyelosis
Presence of jmc

Minor- sub normal erythropoeitin levels

Question 12

Relative or spurious causes of PV

Answer 12

Decreased plasma volume which may be due to dehydration from vomiting, diarrhea
*The Gaisbock syndrome chxd by increased hematocrit levels with normal leukocyte count and no splenomegaly seen in male hypertensive obese patients
*Poor sample collection technique

Question 13

Treatment for Pv

Answer 13

Low risk- phlebotomy + antiplatetlets
High risk- above+ myelosuppression like hydroxyurea, busulfan, interferon,anagrelide
Pregnant women…low dose aspirin +phlebotomy

Question 14

Complications of pv

Answer 14

Leukemogenesis-1.5%
Myelofibrosis- 10-25%

Question 15

Essential thrombocythemia entails

Answer 15

A myeloproliferative neoplasm characterised by the overproduction of platelets (i.e with a count >450×10⁹/L) with extreme megakaryocytic hyperplasia in the bm

Question 16

Is ET primary or secondary thrombocytosis
Why?

Answer 16

Primary, also known as non reactive

Because it is characterised by a clonal disorder of hsc or by inherited mutations (familial or congenital) as opposed to secondary whereby signals promote proliferation of megakaryocytes like cytokine in cases of infection, inflammation etc

Question 17

Absolute causes of erythrocytosis could be grouped into

Answer 17

Secondary and primary

Question 18

Secondary causes of erythrocytosis include

Answer 18

Hypoxia
Inappropriate erythropoietin secretion
Hormonal disorders like cushings
Others like pkd, RAS

Question 19

Primary causes of erthrocytosis

Answer 19

Polycythemia vera
Primary congenital polycythemia
Familial polycythemia

Question 20

Odd one out
Leucocytosis
Splenomegaly
Hemorrhagic and thrombotic events
Leucoerythroblastosis and tear drop cells

Answer 20

Leucoerythroblastosis and tear drop cells (seen in early MF)

Question 21

Symptoms of ET

Answer 21

Typically asymptomatic
Thrombotic events: CVD, DVT,PE,IS
Splenomegaly
Headache visual disturbances

Question 22

A typical presentation of ET in pregnant women

Answer 22

Recurrent first trimester miscarriage due to microcirculatory disturbances and placental microinfarction

Question 23

Epidemiology of pv

Answer 23

2.8/100000 elsewhere
Slight male predominance , median age 60yrs
Seen mostly in ashkenazi Jews, low incidence in Japanese

Question 24

Epidemiology of ET

Answer 24

Annual incidence: 1.5-2.5_/100000
No gender prediliction
50-60 yrs
Ant then 30 yrs(increased risk in females here)

Question 25

Diagnosis of ET

Answer 25

4 major
OR
first 3 major+ minor

Question 26

Major and minor criteria for ET

Answer 26

Platelet count>450 x 10⁹/L
Bone marrow biopsy showing megakaryocytic hyperplasia with absence of fibrosis, dysplasia, or left or right shift in erythropoeisis and granulopoeisis
Not meeting the WHO criteria for PV CML PMF CMML etc
Presence of JAK2(55%), CALR and Mpl mutations

Minor
Presence of a clonal marker or absence of causes of reactive thrombocytosis

Question 27

Differentials of ET

Answer 27

Other causes of reactive thrombocytosis like inflammation, infection, hemolysis, hemorrhage, iron deficiency
Post splenectomy, asplenia, hyposplenism
Malignancy , pregnancy
Other causes of primary like PV cml cmml

Question 28

Treatment of ET

Answer 28

Low risk- low dose aspirin
Low risk with thromvocytosis- low dose aspirin monitor closely
High risk low dose aspirin with cytoreduction
Aspirin- vasomotor symptoms

Question 29

Complications of et

Answer 29

Leukemogemesis and myelofibrosis

Question 30

Primary myelofibrosis

Answer 30

A chronic hematological malignancy chxd by;
Leucoerythroblastosis
Massive splenomegaly
Tear drop poikilocytosis
Bone marrow fibrosis of varying degrees
Bone marrow failure progressively

Question 31

Epidemiology of pm

Answer 31

Male:female - 1:1
Annual incidence- 0.5-1.5/ 100 000
Median age 68years
Worst prognosis, median age of survival 3-5 years

Question 32

Pathogenesis of primary myelofibrosis

Answer 32

The Malignancy originates from totipotent hematopoeitic stem cells that still retain the potentials of differentiating into myeloid and lymphoid cells. This abnormal proliferation results in abnormal cells particularly megakaryocytes that shed growth factors that stimulate fibroblasts to proliferate and deposit collagen leading to abnormal fibrosis of the Bm
Important to note that the marrow fibrosis is not clonal but rather a reactive fibrosis from abnormal stromal cells.

Question 33

Clinical features of primary myelofibrosis

Answer 33

P
R
I
M
A- abdominal discomfort
R
Y

M-massive splenomegaly
Y
E-easy satiety, extramedullary hemopoeisis
L
F-fever
I
B
R
O
S-symptomatic anemia
I
S

Question 34

Diagnosis of pmf

Answer 34

3 major + 1 minor determined on at least 2 examination (BM Biopsy)

Question 35

Major and minor criteria of pmf

Answer 35

Major
Pama…Proliferation and atypia of megakaryocytes accompanied by reticulin and/or collagen fibrosis of grade 2 to 3
Not meeting who criteria for others
Presence of Jmp

Minor
Leucoerythroblastosis
Leucocytosis >11x 10⁹/l
Splenomegaly
Anemia not attributed to a comorbid pathology

Question 36

Treatment of primary myelofibrosis

Answer 36

Palliative
Product support
Sc transplant…only possibility for cure