Myeloproliferative Neoplasms Flashcards
What are myeloproliferative neoplasms?
(previously known as myeloproliferative disorders)
Clonal haemopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells (myeloid lineage)
In contrast to acute leukaemia the maturation is relatively preserved
What can all myeloproliferative neoplasms transform into?
acute myeloid leukaemia
Two broad categories of MPNs?
BCR-ABL1 negative:
- polycythaemia vera (too many red cells)
- essential thrombocythaemia (too many platelets)
- primary myelofibrosis
BCR-ABL1 positive:
-chronic myeloid leukaemia (too many granulocytes)
can be some overlap between disorders
When should you consider a MPN?
high granulocyte count +/- high red cell count/ Hb +/- high platelet count +/- eosinophilia/ basophilia +/- thrombosis in an unusual place
WITH NO REACTIVE EXPLANATION
Explain what chronic myeloid leukaemia is?
proliferation of myeloid cells: granulocytes and their precursors
chronic phase with intact maturation for 3-5 years followed by ‘blast crisis’ reminiscent of acute leukaemia with maturation defect
Clinical features of CML?
can be asymptomatic splenomegaly weight loss sweats anorexia gout can get priapism
Blood count changes in CML?
normal/ reduced Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia, thrombocytosis
What is the hallmark of CML?
philadelphia chromosome
Explain what the philadelphia chromosome is and how it causes disease?
ABL gene (chromosome 9) translocates onto chromosome 22 and fuses with BCR gene get shorter chromosome 22- the philadelphia chromosome and a longer chromosome 9 due to reciprocal translocation the new BCR-ABL1 gene on the philadelphia chromosome produces a tyrosine kinase which causes abnormal phosphorylation (signalling) leading to the haematological changes seen in CML
The BCR-ABL1 negative MPN predominantly affect?
older adults
What BCR-ABL1 negative MPN are more prevalent?
ET and PV
Common clinical features to all BCR-ABL1 negative MPN?
may be asymptomatic due to increased cell turnover: gout, fatigue, weight loss and sweats symptoms and signs of splenomegaly marrow failure increased risk of thrombosis
What is polycythaemia vera?
high Hb/ haematocrit accompanied by erythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages
What is it important to distinguish polycythaemia vera from?
secondary polycythaemia
pseudopolycythaemia
Explain some causes of secondary polycythaemia?
chronic hypoxia from COPD, smoking or sleep apnoea results in increased EPO so more stimulation to increase red cells
or more rarely there is an EPO secreting tumour that results in increased red cells
Explain what can cause a pseudopolycythaemia?
dehydration or diuretics
basically there is a normal amount of red cells but a reduced plasma volume so there is a higher proportion of red cells
Symptoms of PV?
those of MPNs, fatigue, headache, visual disturbance, aquagenic pruritis (itchy after warm bath or shower), thrombosis
Signs of PV?
plethoric (red) and has deep dusky cyanosis, spleen may be enlarged as well as the liver
What mutation is often present in the BCR-ABL1 negative MPNs?
JAK2 mutation
Investigations for PV?
FBC, blood film, JAK2 mutation is present in > 95% so part of diagnostic criteria now and can be tested for in the blood
Management of PV?
Venesection to haematocrit < 0.45
Asprin to reduce risk of thrombosis should be given to all patients unless contraindicated
in some patients oral chemo hydroxycarbamide can be helpful
What is essential thrombocythaemia?
uncontrolled production of abnormal platelets
platelet function is abnormal so there is risk of thrombosis, at high levels can also cause bleeding due to acquired Von Willebrand disease (because VWF is absorbed onto the surface of abnormal platelets)
Clinical features of ET?
those of MPNs, particularly vaso-occlusive symptoms, bleeding, can get erythromelagia which is severe burning pain, erythema and warmth of extremities
Investigations of ET?
high platelet count (must exclude a reactive cause), exclude CML, genetics
What are reactive causes of high platelets that you must exclude to diagnosis ET?
blood loss
inflammation
malignancy
iron deficiency
What are the genetics that can be tested for with ET?
JAK2, CALR, MPL, 10-20% will be triple negative and may be worth doing bone marrow biopsy in these people
Management of ET?
anti-platelets: aspirin to reduce thrombosis risk
in patients considered at higher risk of thrombosis cytoreductive therapy to control proliferation e.g. hydroxycarbamide, anagrelide, interferon alpha
Explain what myelofibrosis is?
debilitating myeloproliferative neoplasm
there is clonal proliferation of stem cells and abnormal myeloid cells in the bone marrow, liver, spleen and other organs, there is also fibrosis in the bone marrow
Clinical features of myelofibrosis?
marrow failure, splenomegaly (LUQ abdo pain, complications including portal hypertensino), massive hypercatabolism with weight loss and night sweats
Investigations for myelofibrosis?
- typical blood film appearance > poikilocytes (tear drop shaped red cells) and leucoerythroblastic film (presence of both neutrophil and red cell precursors in the peripheral blood)
- often difficulties in getting bone marrow aspirate due to fibrosis “dry aspirate”
- fibrosis will be seen on trephine biopsy
(side note: aspirate is when they try to get it with a needle vs trephine where they take out like a proper bit of bone marrow) - check for JAK2, CALR, MPL mutations, 10% will be triple negative
Dry aspirate?
occurs in myelofibrosis because the fibrosis makes it difficult to aspirate
What type of biopsy is needed in myelofibrosis?
trephine biopsy
What is the typical blood film appearance of myelofibrosis?
poikilocytes (tear drop shaped red cells) leucoerythroblastic film (presence of both neutrophil and red cell precursors in the peripheral blood)
What is the name given to tear dropped shaped red cells? What conditions are they present in?
poikilocytes- myelofibrosis
Myelofibrosis may develop as a primary condition or _________
develop late in the course of ET or PV
Explain what is meant by leucoerythroblastic film? What conditions is it present in?
presence of both neutrophil and red cell precursors in the peripheral blood
Reactive (sepsis)
Marrow infiltration (e.g. haematological malignancy infiltration or metastatic infiltration)
Myelofibrosis
What is the prognosis of myelofibrosis?
MF tends to be much more aggressive than ET and PV and can be a life limiting illness
Management of myelofibrosis?
Supportive care: blood transfusions, platelets, antibiotics
allogeneic stem cell transplantation in a select few (only curative treatment but not many are suitable)
splenectomy (not really done now v controversial)
JAK2 inhibitors: no evidence of increased survival but improves quality of life
