Myeloproliferative disorders Flashcards
What is the main difference between the myeloproliferative disorders (MPD) and leukaemia?
Maturation is relatively preserved in MPD
Over-produtction of granulocytes and their precursors
Chronic myeloid leukaemia (CML)
When should an MPD be considered as a diagnosis? (3)
When there is high myeloid cell count, with splenomegaly, and no reactive explanation for this
Three phases of CML
Chronic phase (months to years, few symptoms) Accelerated phase (increasing symptoms and spleen size) Blast crisis (features of acute leukaemia)
What is the pathological hallmark of CML?
Philadelphia chromosome; reciprocal translocation between long arms of chromosome 9 and 22
What does the Philadelphia chromosome (Ph) produce?
BCR-ABL1- abnormal tyrosine kinase
Clinical features of CML (3)
Splenomegaly
Hypermetabolic symptoms
Gout
What is the targeted treatment for Ph+ve CLM?
Imatinib- tyrosine kinase inhibitor
Three main BCR-BL1 negative MPDs
Polycythaemia rubra vera
Essential thrombocythaemia
Idiopathic myelofibrosis
Features that are common to MPDs (8)
May be asymptomatic Gout Fatigue Weight loss Sweats Splenomegaly Marrow failure Thrombosis
What causes marrow failure in MPD?
Fibrosis or leukaemic transformation
Distinguishing feature of polycythaemia rubra vera
High Hb and haematocrit
Causes of secondary polycythaemia (3)
Chronic hypoxia
Smoking
EPO-secreting tumour
Main cause of pseudopolycythaemia
Dehydration
Other than common features of MPD, what are the symptoms of PRV?
Headache
Fatigue
Aquagenic pruritus
Mutation present in 95% patients with PRV
JAK2 point mutation causing uninhibited activation of erythrypoiesis
Treatment of PRV (3)
Venesection to Hct
Uncontrolled production of abnormal platelets
Essential thrombocythaemia
Manifestation of ET (2)
Thrombosis
At high levels can cause bleeding
What should be excluded in a patient with high platelet count? (2)
A reactive thrombocytosis, or CML
What are the typical causes of a reactive thrombocytosis? (4)
Blood loss
Inflammation
Malignancy
Iron deficiency
Mutations in ET (3)
JAK2 (in 50%)
CALR
MPL
Treatment of ET (2)
Anti-platelets Cytoreductive therapy (hydroxycarbamide, interferon alpha)
What are the underlying aetiologies of myelofibrosis? (2)
Idiopathic
Transformation from PRV or ET
Features of idiopathic myelofibrosis (4)
Bone marrow fibrosis on biopsy
Extramedullary haemopoiesis causing hepato/splenomegaly
Leucoerythroblastosis
Teardrop RBCs in blood film
Causes of a leucoerythroblastic film (3)
Reactive (sepsis)
Marrow infiltration
Myelofibrosis
Treatment of MF (2)
Marrow support Allogeneic SCT (selected patients)
