Myeloproliferative Neoplasms Flashcards
What are MPNs
Clonal, hsc diseases that result in excessive and uncontrollable production of cells in one or more cell lineages.
What is seen in mpns typically
Hyperviscosity and organomegaly
Blue book ?
Song
What is the PEP and JMC
P-polycythemia Vera
E-Essential throbocythemia
P- Primary myelofibrosis
JMC -JAK2/MPL/CALR mutation
What is polycythemia vera
A myeloproliferative neoplasm characterised by an absolute increase in red cell mass above the higher interval of normal, with associated thrombocytosis and leukocytosis
Prognosis of PV
Untreated -6-18 months
Treatment with phlebotomy- 3-5 years or 3.5
Treatment with immunosuppression-7-12years
Is PV primary or secondary?…
Why?
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
Symptoms of PV
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
Bleeding and thrombotic events
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
Diagnosis of PV
2 major+1 minor
Or
All 3 major.
Major and minor criteria for PV
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
Relative or spurious causes of PV
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
Treatment for Pv
Low risk- phlebotomy + antiplatetlets
High risk- above+ myelosuppression like hydroxyurea, busulfan, interferon,anagrelide
Pregnant women…low dose aspirin +phlebotomy
Complications of pv
Leukemogenesis-1.5%
Myelofibrosis- 10-25%
Essential thrombocythemia entails
A myeloproliferative neoplasm characterised by the overproduction of platelets (i.e with a count >450×10⁹/L) with extreme megakaryocytic hyperplasia in the bm
Is ET primary or secondary thrombocytosis
Why?
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
Absolute causes of erythrocytosis could be grouped into
Secondary and primary
Secondary causes of erythrocytosis include
Hypoxia
Inappropriate erythropoietin secretion
Hormonal disorders like cushings
Others like pkd, RAS
Primary causes of erthrocytosis
Polycythemia vera
Primary congenital polycythemia
Familial polycythemia
Odd one out
Leucocytosis
Splenomegaly
Hemorrhagic and thrombotic events
Leucoerythroblastosis and tear drop cells
Leucoerythroblastosis and tear drop cells (seen in early MF)
Symptoms of ET
Typically asymptomatic
Thrombotic events: CVD, DVT,PE,IS
Splenomegaly
Headache visual disturbances
A typical presentation of ET in pregnant women
Recurrent first trimester miscarriage due to microcirculatory disturbances and placental microinfarction
Epidemiology of pv
2.8/100000 elsewhere
Slight male predominance , median age 60yrs
Seen mostly in ashkenazi Jews, low incidence in Japanese
Epidemiology of ET
Annual incidence: 1.5-2.5_/100000
No gender prediliction
50-60 yrs
Ant then 30 yrs(increased risk in females here)
Diagnosis of ET
4 major
OR
first 3 major+ minor
Major and minor criteria for ET
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
Differentials of ET
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
Treatment of ET
Low risk- low dose aspirin
Low risk with thromvocytosis- low dose aspirin monitor closely
High risk low dose aspirin with cytoreduction
Aspirin- vasomotor symptoms
Complications of et
Leukemogemesis and myelofibrosis
Primary myelofibrosis
A chronic hematological malignancy chxd by;
Leucoerythroblastosis
Massive splenomegaly
Tear drop poikilocytosis
Bone marrow fibrosis of varying degrees
Bone marrow failure progressively
Epidemiology of pm
Male:female - 1:1
Annual incidence- 0.5-1.5/ 100 000
Median age 68years
Worst prognosis, median age of survival 3-5 years
Pathogenesis of primary myelofibrosis
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.
Clinical features of primary myelofibrosis
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
Diagnosis of pmf
3 major + 1 minor determined on at least 2 examination (BM Biopsy)
Major and minor criteria of pmf
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
Treatment of primary myelofibrosis
Palliative
Product support
Sc transplant…only possibility for cure
