Myeloproliferative Neoplasms Flashcards
Definition
Neoplasm due to proliferation of bone marrow
Polycythaemia vera = red cell proliferation
Essential thrombocythaemia = platelets
Primary myelofibrosis
MPN vs MDS
MPN
- excess production in BM
- increase CBC
MDS
- ineffective production in BM
- decrease CBC
DDx of erythryocytosis
Absolute erythrocytosis (Hb and RBC increase) vs Pseudoerythrocytosis (plasma volume low hence making RBC seem higher than reality e.g. diuretics)
For absolute erythrocytosis:
- primary
- -> polycythaemia vera
- secondary
- -> chronic lung disease/ smoking (hypoxia increase EPO)
- -> OSA
- -> renal cause e.g. artery stenosis, cysts
- -> tumours (paraneoplastic syndrome e.g. RCC, HCC)
- -> drugs e.g. androgen, EPO
Approach to erythrocytosis - Hx, CBC, Ix
Hx:
- suggestion of chronic lung disease, OSA or congenital heart
- rule out any drug use
CBC: trilineage increase in cell count = more suspicious of polycythaemia vera (not expected in secondary causes)
If suspect polycythaemia vera:
- CXR
- JAK2 mutation
- BM biopsy
- -> if JAK2 -ve but BM suggestive –> check serum EPO
- -> if JAK2 and BM both -ve –> sleep study
Diagnostic criteria for polycythaemia vera
Major criteria:
- haemoglobin >16.5 g/dL in men, >16.0 in women
- BM biopsy showing HYPERCELLULARITY with TRILINEAGE growth
- presence of JAK V617F mutation (90% cases +ve) or JAK2 exon 12 mutation
Minor:
- subnormal serum EPO levels
Diagnosis = 3 major or major 1+2 + minor
Treatment and prognosis of PV
Venesection
- remove excess red cells
Aspirin
- prophylaxis for thrombosis
Others (rarely used)
- hydroxyurea, ruxolitinib
Prognosis
- thrombotic risk (higher risk due to polycythaemia causing thicker blood and thrombocytosis; but PV alone also has increased risk!)
- 5% transformation to AML
- progression to marrow fibrosis after 10+ years –> Post PV myelofibrosis
Approach to thrombocytosis
Differentiate reactive (secondary) causes from primary causes - any severe inflammation, Fe deficiency etc may incerase Plt
- review blood film, check acute phase reactants and iron profile
- if reactive thrombocytosis and Fe deficiency ruled out –> repeat blood count
- if persistent thrombocytosis –> molecular testing, BM examination
Diagnostic criteria for Essential Thrombocythaemia
Major criteria:
- Plt >450 x10^9/L
- BM biopsy showing MEGAKARYOCYTIC PROLIFERATION (WBC and RBC usually normal)
- Not meeting criteria for BCR-ABL1+ CML, PV, PMF, MDS or other myeloid neoplasms
- Presence of JAK2, CALR or MPL mutation
Minor criteria:
- presence of clonal marker or absence of evidence for reactive thrombocytosis
Diagnosis = 4 major or major 1-3 + minor
Risks of ET in pregnant and non-pregnant
Irrespective of pregnancy:
- thrombosis (high risk)
- bleeding (when Plt >1400-1500 –> acquired vWF syndrome as more is adsorbed onto Plt surface which decreases vWF in plasma –> decrease clotting)
- transformation to myelofibrosis
- risk of AML very low
Pregnancy:
- foetal loss (severe)
- intrauterine growth retardation
- pre-eclampsia (mild)
Treatment of ET - pregnant vs non-pregnant
Non-pregnant
- Aspirin only
- other options to reduce Plt e.g. hydroxyurea if high risk such as >60 yrs old, anagrelide (less well tolerated)
Pregnant
- Aspirin +/- LMWH (to enhance anti-thrombotic effects)
- alpha interferon (for decreasing platelet count if >1400-1500)
Mutations in MPN
PV
- nearly all cases are JAK2 +ve
ET
- 50% JAK2 +ve
- 25% CALR +ve
- smaller % MPL +ve
- 10-15% non-mutated
PMF
- 50% JAK2
- 30% CALR
- rest is MPL or non-mutated
DDx for HUGE splenomegaly
CML
Myelofibrosis
(malaria, leischmaniasis)
Diagnostic criteria for Primary Myelofibrosis
Major criteria
- compatible marrow picture (megakaryocytic proliferation with mild fibrosis in early phase; fibrotic marrow in late phase with lots of collage and fibrin)
- rule out other MPNs/MDS/CML
- presence of JAK2/CALR/MPLmutations or rule out reactive causes from history
Minor criteria
- anaemia
- leucocytosis >11
- palpable massive splenomegaly
- increased LDH
- leucoerythroblastic blood picture (myelocytes, nucleated RBC, tear drop cells in PB)
Diagnosis = all majors + 1 minor
What is proliferating in PMF?
- Megakaryocytic proliferation mainly
(myelocytes also proliferate initially hence WBC also increases) - Release of various cytokines
- Proliferation of fibroblasts and vessels
- Progression to marrow fibrosis with loss of functions – RBC affected first so anaemia first then leucopenia, thrombocytopenia and marrow failure over time
Risk stratification of PMF and prognosis
IPSS or DIPSS scoring
- >65 yrs old, constitutional symptoms, Hb <10, leucocyte >25, circulating blasts >1% are all poor prognostic indicators
Low risk = 50% survival at 10 yrs
High risk = 50% survival after 1 yr
