Haematology - Non-Leukaemic Myeloproliferative Neoplasms Flashcards

1
Q

What are myeloproliferative neoplasms? Name 3 important neoplasms

A
  • Myeloproliferative neoplasms: group of conditions arising from marrow stem cells and characterised by clonal proliferation of one or more haemopoietic components in the BM, the liver and spleen.
  • These neoplasms are closely related to each other and transitional forms can occur with evolution from one entity to another during the course of the disease.

The three main non-leukemic disorders included in this classification are:

  • Polycythaemia Vera
  • Essential thrombocytopenia
  • Primary myelofibrosis
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2
Q

Name an important gene that is associated with these three conditions

A

These diseases are associated with clonal abnormalities involving genes that encode cytoplasmic or receptor tyrosine kinase

  • Single acquired mutation of cytoplasmic tyrosine kinase Janus-associated kinase 2 (JAK 2) occurs in marrow and blood of almost all patients with PV, and in approx. 50% of patients with ET and myelofibrosis
  • JAK 2: has major role in normal myeloid development by transducing signals from diverse cytokines and growth factors (IL3, GM-CSF and G-CSF).
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3
Q

What is polycythaemia vera? Name some important investigation findings

A
  • Uncontrolled production of red cell volume - caused by a clonal malignancy of a marrow stem cell
  • A mutation in JAK2 is found in over 95% of patients
  • Investigation findings:
    • FBC: increase in red cells (diagnostic finding), haematocrit (raised)
    • Overproduction of granulocytes (neutrophils, eosinophils and basophils)
    • Thrombosis
    • low serum EPO levels
    • Raised LDH
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4
Q

Polycythaemia vera: important clinical findings

A
  • Disease of older subjects with equal sex incidence, clinical features are the result of hyperviscosity, hypervolaemia and hypermetabolism
  • Headaches, dyspnea, blurred vision and night sweats + pruritus after a hot bath (can be very severe)
  • Plethoric appearance: ruddy cyanosis and retinal venous engorgement
  • Splenomegaly
  • Haemorrhage or thrombosis (arterial or venous)
  • HTN
  • Gout (as a result of raised uric acid production)
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5
Q

Polycythaemia Vera: treatment

A
  • Aimed at maintaining normal blood count: haematocrit should be >0.45 and platelet count <400 x 10^9/L
  • Venesection: useful and rapid – good for younger and milder disease patients (does not control platelet count)
  • Cytotoxic myelosuppression: aspirin, hydroxycarbamide, peggylated interferon

*Always give allopurinol when initiating treatment to prevent TLS induced AKI

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6
Q

What is essential thrombocythaemia?

A

Definition: sustained increase in platelet count due to megakaryocyte proliferation and overproduction of platelets.

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7
Q

What investigations should you perform in essential thrombocythaemia?

A
  • Bloods:
    • Persisting platelet count >450 x 10^9/L (main diagnostic criteria)
    • Haematocrit is normal and the Philadelphia chromosome or BCR-APL 1 rearrangement are absent
  • JAK2 mutation present in 50% of cases
  • BM trephine:
    • Shows increased megakaryocytes with prominent large hyperlobulated forms
    • Does not have collagen fibrosis
  • Blood film:
    • Abnormal large platelets and megakaryocyte fragments

*Need to exclude other causes of raised platelet count (iron deficiency, inflammatory or malignant disorder, and myelodysplasia) before can diagnose ET.

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8
Q

Give some clinical features of essential thrombocythaemia

A
  • Thrombosis and haemorrhage (acute or chronic) are main clinical features but most cases are asymptomatic
  • Splenomegaly (unless is atrophic due to infarction)
  • Erythromelalgia: burning sensation in hands and feet relieved by aspirin
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9
Q

Outline the treatment for essential thrombocythaemia

A
  • Principle is to reduce risk of thrombosis and haemorrhage – may need splenomegaly
  • Risk factors: >60 years old, JAK2 mutation, smoking, HTN, previous thrombotic episodes
  • Low dose aspirin (75mg/day) for all at risk patients, higher risk patients can get chemotherapy (hydroxycarbamide) or interferon
  • Course of disease: often stationary for 10-20 years – may transform after a number of years to myelofibrosis but risk of transformation to acute leukaemia is low.
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10
Q

What is primary myelofibrosis?

A

Definition: progressive generalised reactive fibrosis of BM in association with the development of haemopoiesis in the spleen and liver (myeloid metaplasia).

  • Myelofibrosis is a clonal stem cell disease –fibrosis of BM is secondary to hyperplasia of abnormal megakaryocytes.
  • It is thought that fibroblasts are stimulated by platelet derived growth factor and other cytokines secreted by megakaryocytes and platelets.
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11
Q

Outline some clinical features of primary myelofibrosis

A
  • Insidious onset in older people + symptoms of anaemia
  • Massive splenomegaly (main physical finding): abdo discomfort, pain indigestion
  • Hypermetabolic symptoms: weight loss, anorexia, fever, night sweats
  • Bleeding problems, bone pain or gout (minority of patients)
  • Transformation into acute myeloid leukaemia occurs in 10-20% of patients.

*Primary fibrosis and CML are responsible for most cases of massive (>20cm) splenic enlargement in UK and North America

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12
Q

Outline some investigation findings for primary myelofibrosis

A
  • Bloods:
    • Anaemia
    • Raised WCC and platelets at presentation (later in disease get leukopenia and thrombocytopenia)
    • Leucoerythroblastic blood film: ‘tear drop’ poikilocytes and nucleated RBCs
    • Jak 2 kinase in >50% cases
    • Raised serum urate and LDH: reflects increased but ineffective turnover of haemopoietic stem cells.
  • BM findings:
    • Aspiration normally unobtainable
    • Trephine biopsy: BM architecture is lost and haemopoietic cells are surrounded by increased fibrous tissue and intercellular substance. Increased megakaryocytes
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13
Q

Outline the treatment options for primary myelofibrosis

A
  • Supportive care:
    • Blood transfusions
    • Regular folic acid
    • Splenectomy to relieve sx of splenomegaly
    • Allopurinol: prevents gout and urate nephropathy from hyperuricaemia
  • Cytotoxic drugs: hydroxycarbamide, JAK 2 inhibitors, SCT (high risks associated with transplants)
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