myeloproliferative neoplasms

The Myeloid Malignancies

Clonal proliferation of mature myeloid cells.

• Key Divide: Philadelphia Chromosome Positive (CML) vs. Negative (PV, ET, PMF).
• Key Risk: Transformation to Acute Leukaemia (AML) or progression to Myelofibrosis.

1. chronic myeloid leukaemia (cml)

• Identity: “Too many granulocytes” (Neutrophils, Basophils, Eosinophils).
• Pathophysiology: t(9;22) Translocation $\to$ Philadelphia Chromosome $\to$ BCR-ABL fusion gene.
• Diagnosis: Peripheral blood PCR for BCR-ABL transcripts.

phase definitions (who vs. eln)

Note: WHO 2022 removed the “Accelerated Phase” (biphasic model), but many clinical trials/guidelines (ELN/MD Anderson) retain the triphasic definition.

Phase	WHO 2022 (Pathology)	ELN / MD Anderson (Clinical/Trials)
Chronic	Blasts < 20%	Blasts < 15%
Accelerated	Removed	Blasts 15–29% OR Basophils $\ge$ 20%
Blast	Blasts $\ge$ 20%	Blasts $\ge$ 30%

management

• First Line: Tyrosine Kinase Inhibitors (TKIs).
  • Imatinib (1st gen).
  • Dasatinib, Nilotinib (2nd gen) - Preferred if high risk (e.g. ELTS score).
• Monitoring: Serial BCR-ABL transcript levels (Molecular Response).
• TKI Adverse Effects:
  • General: Myelosuppression.
  • Dasatinib: Pleural effusions, Pulmonary HTN.
  • Nilotinib: QT prolongation, vascular events (PAOD).

2. polycythaemia vera (pv)

• Identity: “Too many RBCs” (Independent of EPO).
• Pathophysiology: JAK2 V617F mutation (>95% of cases).
• Diagnosis (WHO):
  • Major: Hb > 165 g/L (Men) / > 160 g/L (Women) OR Hct > 0.49/0.48 PLUS Bone Marrow (Hypercellular/Panmyelosis) PLUS JAK2 mutation.
  • Minor: Low serum EPO.
• S/Sx: Erythromelalgia (burning hands/feet), Aquagenic Pruritus (itchy after shower), Thrombosis (Arterial/Venous).

risk stratification & management

Goal: Prevent thrombosis and haemorrhage.

| Risk Category | Criteria | Treatment | | :--- | : --- | : --- | | Low Risk | Age < 60 AND No Hx of Thrombosis. | Phlebotomy (Target Hct < 0.45) + ASA 81mg. | | High Risk | Age $\ge$ 60 OR Hx of Thrombosis. | As above + Cytoreduction (Hydroxyurea). |

• Second Line: Interferon (young/pregnant) or Ruxolitinib (JAK inhibitor).

3. essential thrombocythaemia (et)

• Identity: “Too many platelets”.
• Pathophysiology: JAK2 (~60%), CALR (~20-25%), or MPL (~3-4%).
• Diagnosis:
  • Platelets $\ge$ 450 $\times$ 10${}^9$/L.
  • Biopsy: Hyperlobulated megakaryocytes.
  • Exclusion of reactive causes (Iron deficiency, infection, inflammation).

exam trap: acquired von willebrand syndrome

Extreme thrombocytosis consumes vWF multimers, causing a paradoxical bleeding risk.

• Definition: “Extreme” is typically $\ge$ 1,000 $\times$ 10${}^9$/L, but risk is continuous.
• Action: If Platelets $\ge$ 1,000 (or bleeding Hx), check vWF Activity (Ristocetin Cofactor).
• Safety: If vWF activity < 30%, HOLD ASA to avoid haemorrhage.

management (revised ipset)

• Very Low Risk (Age <60, JAK2 neg): Observe or ASA.
• Low/Intermediate: ASA 81mg.
• High Risk (Age >60 OR Hx Thrombosis OR JAK2 pos): ASA + Hydroxyurea.

4. primary myelofibrosis (pmf)

• Identity: “The burnt out marrow.”
• Pathophysiology: Clonal proliferation $\to$ Marrow Fibrosis $\to$ Extramedullary Haematopoiesis.
• S/Sx: Massive Splenomegaly (spleen takes over production), B-Symptoms (weight loss, fevers).
• Diagnosis:
  • Peripheral Smear: Leukoerythroblastic picture (nucleated RBCs + left shift) + Teardrop Cells (dacrocytes).
  • Marrow: Significant fibrosis (“Dry Tap”).
  • Genetics: JAK2, CALR, or MPL.

management

• Curative: Allogeneic Stem Cell Transplant (High risk/Young patients).
• Symptomatic (Spleen/Constitutional): Ruxolitinib (JAK inhibitor).
• Supportive: Transfusions, EPO.

related pages: unusual site thrombosis, Acute Myeloid Leukaemia, Splenomegaly