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Myeloproliferative disorders

Specialties > Haematology

Background knowledge 🧠

Definition

  • Myeloproliferative disorders (MPDs) are a group of clonal hematopoietic stem cell disorders characterized by the overproduction of one or more types of blood cells.
  • This group includes conditions like Polycythaemia Vera (PV), Essential Thrombocythaemia (ET), Primary Myelofibrosis (PMF), and Chronic Myeloid Leukaemia (CML).
  • They are associated with mutations in the JAK2, CALR, and MPL genes.

Epidemiology

  • MPDs are rare, with an estimated prevalence of around 1-2 per 100,000 people.
  • They are more common in adults, typically diagnosed in patients aged 50-70 years.
  • There is a slight male predominance in CML and PV.
  • Incidence increases with age.

Aetiology and Pathophysiology

  • Exact cause is unknown, but genetic mutations play a crucial role.
  • JAK2 V617F mutation is present in approximately 95% of PV cases and 50-60% of ET and PMF cases.
  • CALR and MPL mutations are also associated, especially in JAK2-negative ET and PMF.
  • Mutations lead to constitutive activation of tyrosine kinases, promoting cell proliferation and resistance to apoptosis.
  • Chronic myeloid leukaemia is characterized by the BCR-ABL fusion gene (Philadelphia chromosome).

Types

  • Polycythaemia Vera (PV): Increased red cell mass and often elevated white blood cells and platelets.
  • Essential Thrombocythaemia (ET): Characterized by a sustained elevation in platelet count.
  • Primary Myelofibrosis (PMF): Marrow fibrosis, splenomegaly, and extramedullary hematopoiesis.
  • Chronic Myeloid Leukaemia (CML): Defined by the presence of the BCR-ABL fusion gene.

Clinical Features 🌡️

Symptoms

  • Fatigue and malaise are common across all MPDs.
  • PV: Headaches, dizziness, pruritus (especially after hot baths), and erythromelalgia.
  • ET: Often asymptomatic; may present with erythromelalgia, visual disturbances, or thrombotic events.
  • PMF: Early satiety, weight loss, night sweats, and abdominal discomfort from splenomegaly.
  • CML: Often asymptomatic in chronic phase; may present with fatigue, weight loss, and splenomegaly.

Signs

  • Splenomegaly is common in PV, PMF, and CML.
  • Hepatomegaly may be present, particularly in PMF.
  • Plethora and hypertension in PV.
  • Thrombosis or bleeding complications in ET.
  • Leukocytosis and thrombocytosis often found incidentally in CML.

Investigations 🧪

Tests

  • Full Blood Count (FBC): Elevated red cell mass in PV, thrombocytosis in ET, leukocytosis in CML.
  • Bone Marrow Biopsy: Hypercellularity in PV and ET, fibrosis in PMF, and Philadelphia chromosome in CML.
  • JAK2 V617F mutation analysis for PV, ET, and PMF.
  • BCR-ABL fusion gene test for CML diagnosis.
  • Serum erythropoietin levels: Low in PV.

Management 🥼

Management

  • PV: Phlebotomy, low-dose aspirin, and cytoreductive therapy (e.g., hydroxycarbamide) for high-risk patients.
  • ET: Low-dose aspirin; cytoreductive therapy for high-risk patients.
  • PMF: Supportive care, JAK2 inhibitors (e.g., ruxolitinib), allogeneic stem cell transplantation in suitable patients.
  • CML: Tyrosine kinase inhibitors (e.g., imatinib), regular monitoring of BCR-ABL levels.

Complications

  • Thrombosis (e.g., stroke, deep vein thrombosis) in PV and ET.
  • Progression to myelofibrosis or acute myeloid leukaemia, particularly in PMF.
  • Bleeding complications, especially in ET.
  • Splenic infarction or rupture in CML.
  • Transformation to blast phase in CML, resembling acute leukaemia.

Prognosis

  • PV and ET generally have good long-term survival with appropriate management.
  • PMF has a more variable prognosis, often poorer due to risk of progression to acute leukaemia.
  • CML has a good prognosis with the use of tyrosine kinase inhibitors, with many patients achieving long-term remission.
  • Regular follow-up is essential for monitoring disease progression and managing complications.

Key Points

  • MPDs are clonal disorders characterized by the overproduction of blood cells.
  • JAK2 mutation is a common driver in PV, ET, and PMF.
  • Management involves controlling cell counts and preventing thrombotic events.
  • Regular monitoring is crucial for early detection of complications.
  • CML is treated effectively with tyrosine kinase inhibitors, offering good prognosis.

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Haematology