CP7-10 chronic myeloproliferative disorders Flashcards
What is chronic myeloid leukaemia?
A long-lasting cancer arising from white blood cells deriving from myeloid cells e.g. basophils, neutrophils and eosinophils
What is the epidemiology of chronic myeloid leukaemia?
Less than 1% of cancer cases
Peaking in 85-89 year olds
Between 800 cases per year in the UK
Rates are decreasing
What chromosome is associated with chronic myeloid lymphoma?
Philadelphia chromosome which results due to translocation of ABL1 gene from chromosome 9 to adjacent to the BCR gene of 22 forming the BCR-ABL gene
What does BCR-ABL gene do?
induces mitogenesis (i.e. increases rate of division) of fibroblast and hematopoietic cells and protects cells from apoptosis
What drugs are used to treat chronic myeloid leukaemia?
Imatinib (and other -tinib drugs)
What are significant results in a FBC that suggest a patient has CML?
With WCC ranging from just above normal to >500
Anaemia is common
Platelets are raised
What WBC are increased in the blood in CML?
Neutrophils
Myelocytes
Eosinophils
Basophils
Small blast cells - slightly but not as much as in acute myeloid leukaemia
How may a patient with CML present?
Potentially asymptomatic
Headache
Blurred vision
Night sweats
Fatigue
Bone pain (less common)
Abdominal pain or swelling due to enlarging spleen (spleen become palpable)
SoB
Bruising or bleeding
Weight loss
Priapism (persistent and painful erection)
Hyperviscosity syndrome
What is polycythaemia?
Increased Hb and haematocrit in the blood.
What is the BCSH guidelines for diagnosing polycythaemia?
> 0.48 haematocrit count in females and >0.52 in males sustained for more than 2 months
What categories are polycythaemia divided into?
Congenital
Acquired
What are some secondary causes of polycythaemia?
Appropriate reaction to low oxygen:
- Lung or cyanotic heart disease
- High altitude
- Sleep apnoea
- Renal hypoxia due to artery stenosis or cysts
Lifestyle:
- smoking
- alcohol
- sports performance enhancing drugs
Testosterone treatment
What are some congenital causes of polycythaemia?
High affinity haemoglobin
EPO receptor mutation
Defect in oxygen sensing pathway
What are some causes of acquired polycythaemia?
Primary polycythaemia
Secondary polycythaemia
Idiopathic erythrocytosis
What are come cancers that can cause secondary polycythaemia due to ectopic erythropoietin secretion?
Renal tumours
Uterine Tumours
Hepatocellular carcinoma
Cerebella haemangioma
Parathyroid tumours
What mineral deficiency can disguise polycythaemia?
Iron deficiency
What blood findings are found in polycythaemia?
Sustained raised haematocrit
Low MCV
50% will have raised white cell count or raised platelets
Basophilia and or eosinophilia
How are patients with potential polycythaemia assessed?
Through history - social and family specifically
Examination - can the spleen be palpated and oxygen sats
Chest X-ray
Blood tests
Potential further tests:
- US abdomen
- Head and neck CT
- Gene sequencing
What genetic mutation is associated with polycythaemia?
Jak 2 mutation
How can Jak 2 mutation cause primary polycythaemia?
gives myeloid progenitor cells a survival advantage and causes clonal overproliferation
How do patients with polycythaemia present?
Headache
Blurred vision
Fatigue
Itching - aquagenic pruritus
+/- splenomegaly
Thrombosis
Gout
Not as common but erythromelalgia
How is polycythaemia treated?
Low dose aspirin
Venesection
Low dose chemotherapy e.g. with hydroxycarbamide
What are potential complications of polycythaemia?
Transformation into acute leukaemia in 2% after 10 years
Increase risk of transformation into myelofibrosis
What is essential thrombocythaemia?
A myeloproliferative neoplasm where there is a raised platelet count +/- raised WCC
What causes reactive thrombocytosis?
Bleeding
Iron deficiency
Post-operative
Infection
Inflammation
Malignant disease
How do patients with essential thrombocytopenia present?
Often asymptomatic and picked up on routine testing
Pruritus
Erythromelalgia
Thrombosis in 20-30% of patients
What disease causes a high platelet count associated with paradoxical higher bleeding risk?
Acquired vWD
When gene mutations are associated with essential thrombocytopenia?
JAK2
CALR
MPL
When is a bone marrow biopsy taken?
If unexplained cause of thrombocytopenia/ nothing picked up genetically
How is bone marrow morphology characterised in patients with essential thrombocytopenia?
Larger megakaryocytes forming loose clusters
What is myelofibrosis?
Fibrosis due to an interaction between coronal megakaryocytes producing microbes such as PDGF increasing fibroblast proliferation
What is the risk of myelofibrosis transforming into acute myeloid leukaemia?
10-20% after 10 years
What are the pathology in patients with myelofibrosis?
In leucoerythroblastic blood film:
- Immature white and red cells
- initial increase in platelets and normal Hb
- develops into bone marrow failure with pancytopenia
Bone marrow biopsy:
- initially hypercellular +/- pre-fibrotic phase
- unlit at Ely hypocellular eith increase fibrosis on reticulin staining
What is extramedullary haemopoiesis?
Production of blood cells in organs other than the bone marrow e.g. spleen or liver
What commonly causes extramedullary haemopoiesis?
Myelofibrosis
How do patients with myelofibrosis present?
Generally unwell
Anaemia
Bruising/bleeding
Increased infections
Fever, weight loss, drenching night sweats, bone pain
early hunger
Pain due to splenomegaly
Capsular distension in spleen or splenic infarct
How is myelofibrosis treated?
Erythropoietin or transfusion for anaemia
Ruxolitinab
Splenectomy
Stem cell transplant in younger and high risk patients
How does the drug ruxolitinib work?
Inhibits Jak2
