Myeloproliferative Disorders Notes

Myeloproliferative Disorders

A group of four disease caused by clonal proliferation of haemopoeitic stem cells

• Chronic myeloid leukaemia

• Myelofibrosis

• Polycythaemia ruba vera

• Essential throbocythaemia

Chronic myeloid leukemia

Clonal proliferation of myeloid precursor cells (neutrophils, basophils, eosinophils)

Chronic = abnormality further down the cell line therefore more differentiated cells

= More treatable

Pathogenesis

• Presence of Philadelphia chromosome (9:22 translocation forming bcr-abl gene)

  • Produces a protein that is thought to be oncogenic

Clinical features

• 3 distinct clinical phases

Primary = chronic phase – symptoms of anaemia, anorexia and weight loss

May have marked splenomegaly. Neutropenia or thrombocytopenia not usually present

Secondary = accelerated phase – insidious deterioration. Requires increased amount of treatment to control spleen size and WCC

Tertiary = blast phase – usually fatal. Presents as an acute leukaemia

Diagnosis

• Blood count

  • Raised WCC – usually >100/10x9

  • Low Hb

  • Low platelets

• Film

  • Shows increasing numbers of morphologically normal myelocytes and neutrophils

  • Basophilia

  • Blast cells

• BM aspirate and trephine

  • Less useful

  • Cytogenetics show Philadelphia chromosome (in 95% of cases)

Management

• Chronic phase

  • Chemo

  • Alpha interferon

  • Allogeneic stem cell transplant – only cure

  • Imatanib – tyrosine kinase inhibitors for Philadelphia chromosome BCR-abl gene) – targeted treatment

• Blast crisis

  • Management as for acute leukaemia

  • Can induce remission back into ‘chronic phase’ – temporarily

Prognosis

• Best predictor = initial response to treatment

• Can monitor with blood counts and cytogenetics (ph. Cr disappears therefore bcr-abl reduces)

Myelofibrosis

Clonal proliferation of haemopoeitic stem cells, which release growth factors

• Particularly platelet-derived growth factor and cytokines

Epidemiology

• Mean age of presentation = 60years

Clinical features

• Anaemia

• Splenomegaly (often painful and massive)

• Systemic symptoms

  • Weight loss

  • Fever

Investigations

• FBC

  • Anaemia

  • Raised WCC

  • Raised platelets

• Blood film

  • Immature red and white cells (leukoerythroblastic change)

  • Tear-drop RBC

• Bone marrow aspirate and trephine

  • BM often inaspirable due to fibrosis

  • Trephine biopsy is hypocellular with increased marrow fibrosis

Management

• Supportive treatment

  • Blood transfusion, anabolic steroids and EPO for anaemia

  • Splenectomy useful in painful splenomegaly or to reduce transfusion requirements

• Hydroxyurea can be used to control high WCC and reduce spleen size

  • But has no impact on marrow fibrosis

Prognosis

• Median survival 4 years

• Poor prognostic factors = increasing age, anaemia, leukopenia, abnormal marrow karyotype

Polycythaemia

An increase in Hb > 2 standard deviations from the mean

Primary (Polycythaemia rubra vera)

• Myeloproliferative disease

• Clonal stem cell disorder

• High red cell mass (half of patient have a high platelet count too)

Clinical features

• Common complications of PRV are vascular

  • TIA, strokes, MI, DVT, PE

• Other features

  • Facial plethora

  • Itching, particularly after a hot bath/shower (aquagenic pruritis)

  • Burning discomfort in extremities +/- reddish/blue discolouration (erythromelalgia) caused by slow blood flow and platelet aggregation in small arterioles

  • Splenomegaly

  • Bruising/bleeding may occur due to reduced platelet function

Secondary

• Increased erythropoiesis production in response to

  • Hypoxia (lung disease, cyanotic heart disease)

• Exogenous erythropoiesis production with no stimuli (renal, adrenal + cerebellar tumours)

Relative

• Reduction in plasma volume with normal RBC count – ‘apparent polycythaemia’

• Due to

  • Alcohol

  • Diuretics

Clinical...

Buy the full version of these notes or essay plans and more in our Haematology Notes.