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Myeloproliferative Disorders

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by

Louise Hagerty

on 7 December 2015

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Transcript of Myeloproliferative Disorders

Myeloproliferative
disorders
Increase in red cell volume due to a CLONAL malignancy of a marrow stem cell

May also have ↑neutrophils and platelets
Polycythaemia Rubra Vera
JAK2 Mutation

Leads to cell proliferation as JAK2 protein is constitutively activated
Clinical Features due to

HYPERviscosity
HYPERvolaemia

(HYPERmetabolism & Haemolysis)
Headaches & dizziness
Visual disturbances
Tinnitus
Pruritis (HOT BATH!)
Erythromelalgia
Gout (↑ urate)
Plethoric complexion
Splenomegaly
Thrombosis
Haemorrhage
FBC:
↑ red cell count
↑ packed cell volume
↑ haemoglobin
Blood Film
JAK2 mutation
Serum Ferritin
EPO low
Bone marrow


Management
No cure
VENESECTION
Low dose aspirin
Cytotoxic drugs e.g. hyrdoxycarbamide if symptomatic splenomegaly
Radioactive phosphorus if over 70 - risk of leukaemia



Prognosis

Most people remain well!
Thrombosis / haemorrhage - main complications

30% progress to myelofibrosis
5% progress to acute leukaemia

MONITOR FBCs
Essential Thrombocythaemia
CLONAL proliferation of megakaryocytes leads to ↑ PLATELETS (thrombocytosis) with impaired function
~50% have JAK2
Features:
Bleeding
Thrombosis
Microvascular occlusion
headaches
dizziness
erythromelalgia
Splenomegaly
Investigations:

FBCs (+ repeat)
Platelets persistently over 600x10^9/L
Exclude other causes e.g. reactive due to bleeding, infection, malignancy, chronic inflammation
ESR, CRP, Fibrinogen - NORMAL
Low dose ASPIRIN
+
Hydroxycarbamide if...
>60
Previous thrombosis
Plts over 1500

Causes myelosuppression so reduces plts!


Can progress to...

MYELOFIBROSIS
or
ACUTE LEUKAEMIA

Myelofibrosis
Marrow SCARRING due to hyperplasia of megakaryocytes which cause ↑ production of platelet derived growth factor.

Myeloid metaplasia -->
massive
HEPATOSPLENOMEGALY

JAK2 - 50-60% of patients
Investigations
FBC
Plts initially high then thrombocytopenia
Low red cell count
WCC - high or low!
Blood film
Teardrop RBCs
Leukoerythroblastic cells
Bone marrow aspirate - DRY
Bone marrow trephine - diagnostic - shows fibrosis
Treatment
Under 50
Myeloblative bone marrow transplant (allogeneic stem cell transplant)
50-65 year olds
Non-myeloblative bone marrow transplant
Over 65
Spleen reduction - medically (e.g. thalidomide) or surgically (splenectomy)
Marrow support - platelet / blood transfusions
Stem cell transplant can be curative in younger patients.

Prognosis if no transplant - median survival of 5 years

Trial - JAK2 inhibitors
PRESENTATION

Constitutional symptoms

Abdominal discomfort - big spleen!

BONE MARROW FAILURE
Anaemia
Infections
Bleeding

CML
Uncontrolled clonal proliferation of myeloid precursors which still have their ability to differentiate intact - malignancy of granulocytes

Mostly 40-60 yr olds but can be younger
Different phases:
Chronic - few symptoms - can last years!
Accelerated - increasing symptoms and splenic size - symptoms from cellular accumulation
Acute - blast transformation; symptoms from marrow failure
FBC:
↑↑↑ WCC (often >100x10^9 / L)
Neutrophils, basophils, eosinophils, myelocytes
↓ Hb (or normal) / Plts variable

Urate and B12 ↑

Bone marrow - hypercellular

Cytogenetics - look for Philly!
Molecular test on blood - BCR-ABL FISH


Presentation:
Insidious onset
Weight ↓
Fatigue
Sweats
Fever
Abdominal discomfort - SPLENOMEGALY
t(9;22)


PHILADELPHIA Chromosome


BCR-ABL gene


Tyrosine kinase
IMATINIB
tYROSINE kINASE iNHIBITOR
UNCONTROLLED PROLIFERATION OF ONE OR MORE OF THE MYELOID STEM CELL LINE

Cells look quite NORMAL
Can progress to acute leukaemia - cells look ABNORMAL
Louise Hagerty
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