40 Myeloproliferative disorders + CML Flashcards
Name the three myeloproliferative disorders.
Polycthaemia vera.
Essential thrombocytosis.
Idiopathic fibrosis.
What is the blood abnormality in polycythaemia vera?
Increased RBCs ± increased neutrophils and platelets.
What are the clinical features of polycythaemia vera? (8).
Insidious. Itching. Plethoric face. Headache and general malaise. Tinnititus. Peptic ulcer. Gout. Engorged retinal veins. Splenomegaly.
Which tests are used to distinguish between the different types of polycythaemia? (4).
FBC.
Ferritin.
Epo (erythropoietin) level.
U&Es/LFTs.
How is 1o polycythaemia differentiated from 2o?
1o: RBC production with low EPO.
2o: EPO raised.
Name five causes of secondary polycythaemia:
Any central hypoxic process. Renal disease. EPO producing tumour. Drug associated (androgens, post renal transplant). Congenital.
Which tests should be done in polycythaemia vera? (3).
JAK2 mutation.
Bone marrow examination.
EXON12 mutation.
What is the JAK2 mutation?
Nucleotide?
Amino acid?
Mechanism?
In JH2 domain (inactive).
G-T mutation at nucleotide 1849.
V617F (phenylalanine for valine ar 617).
Destroys BsaXI site.
What does the JAK2 mutation do? (2)
Promotes cell division.
EPO no longer needed to turn on EPO receptors.
What is the JAK2 mutation diagnostic of?
A myeloproliferative disorder.
What is the treatment for polycythaemia vera?
Risks?
Survival?
Venesection, aspirin.
Progression to AML and myelofibrosis.
15 years.
What is thrombocytosis?
Increased platelets.
What are the causes of thrombocytosis?
1o: essential.
2o: reactive (surgery, infection, malignancy, low iron, hyposplenism, haemolysis, drug).
What are the 1st and 2nd line investigations for thrombocytosis?
1: Blood film, ferritin,CRP, CXR, ESR.
2: JAK and CALR mutations.
What is the CALR mutation?
What does it do?
Who is it found in?
Calreticulin mutation in exon 9 of gene.
Activates cell signalling pathways.
+ve in 90% of JAK2 -ve essential thrmobocytosis.
How is essential thrombocyosis treated? (1,4)
Survivial?
Aspirin.
If high thrombotic risk then cytoreduction: hydroxycarbamide, interferon, anagrelide, P32.
20 years.
How does myelofibrosis present? (5)
Pancytopoenia.
B symptoms: night sweats, fever, weight loss.
Massive splenomegaly.
How is myelofibrosis diagnosed? (3)
Blood film.
Bone marrow results.
JAK2/CALR mutation.
What is the treatment and prognosis of myelofibrosis?
Supportive, JAK2 inhibitors, BM transplant.
Poor - 5 year median survival.
Who gets chronic myeloid leukaemia?
55-60y/o.
M 1.5 : 1 F
What are the characteristics of CML? (4).
Leucocytosis.
Leucoerythroblastic blood film.
Anaemia.
Splenomegaly.
What are the symptoms of CML? (4).
Abdominal pain.
Fatigue from anaemia.
Venous occlusion: retinal, DVT, priapism.
Gout.
What is the common genetic defect in CML?
BCR-ABL fusion gene coding for active tyrosine kinase.
Philadelphia chromosome. 9:22 translocation.
Which drug is used in CML?
How does it work?
Gleevec (imatinib).
Blocks active site of bcr-abl tyrosine kinase.
How does imatinib resistance occur?
New treatment? (2)
Activating loop mutations in BCR-ABL.
Nilotinib, Dasatinib.
Differentiate between CML and CLL.
CML: Leucocytosis.
CLL: Leucocytosis of which 99% are B cells.
What is the clinical course of CLL? (2)
Rx? (3)
Most commonly occurs in older patients who die of other diseases.
In young, more aggressive - treat with fludarabine, cyclophosphamide and rituximab.
What is the prognosis with imatinib treated CML?
95% 5 year survival.
