Myeloproliferative Neoplasms (MPNs)
Sally Momoh
Background
- Chronic myeloid neoplasms marked by clonal proliferation of mature, well-differentiated myeloid cells.
- Unlike MDS, cells are typically non-dysplastic.
- Types of MPNs: polycythemia vera, essential thrombocythemia, primary myelofibrosis and chronic myeloid leukemia.
- Complications include thrombosis, bleeding, or transformation to acute myeloid leukemia (AML) or a fibrotic phase.
Polycythemia Vera (PV)
Background
- Polycythemia: Hb/Hct = Men > 16.5/49%; Women > 16/48%.
- Relative polycythemia: decreased plasma volume (e.g diuretics, dehydration).
- Absolute polycythemia: increased RBC mass.
- Primary: acquired mutation JAK2 V617F (or JAK2 Exon 12).
- Secondary: elevated erythropoietin (EPO) from hypoxia (COPD, OSA, smoking), renal disease, EPO-secreting tumors, or steroid use.
Presentation
- Incidental.
- Hyperviscosity symptoms: Headache, visual disturbances, aquagenic pruritus, erythromelalgia, splenomegaly.
- Aquagenic pruritis.
- Risks of thrombosis and bleeding.
Evaluation
- CBC w/ diff and peripheral smear.
- EPO level.
- JAK2 mutation testing.
Management
- Phlebotomy (goal Hct <45%).
- Low-dose aspirin reduces thrombosis and vasomotor symptoms.
- High-risk or refractory patients require cytoreduction (hydroxyurea, interferon-α, ruxolitinib in select cases).
Essential Thrombocythemia (ET)
Background
- Clonal thrombocytosis (>450,000/μL).
Presentation
- Incidental.
- Vasomotor symptoms: Headache, blurred vision, erythromelalgia, arterial/venous thrombosis.
- Symptoms often improve with low-dose aspirin.
- Risks of thrombosis and bleeding.
Evaluation
- Exclude reactive thrombocytosis (infection, inflammation, bleeding, iron deficiency, postsplenectomy).
- Smear with platelet anisocytosis.
- Dacrocytes (teardrop-shaped red blood cells) suggest to post-ET myelofibrosis.
- CMP, LDH, uric acid.
- BCR-ABL1 testing to exclude CML.
- Molecular testing (JAK2, CALR, MPL).
Management
- Avoid aspirin if platelets >1 million/μL if presence of acquired von Willebrand syndrome.
Treatment of ET
| Risk Score (IPSET-thrombosis) |
Features |
Treatment |
| High |
Age >60 with JAK2, prior thrombosis |
Hydroxyurea (target plt 100-400k) or IFNa + low-dose aspirin
|
| Intermediate |
Age >60, no JAK2, no thrombosis |
Aspirin ± cytoreduction |
| Low |
Age ≤60 with JAK2, no thrombosis |
Aspirin |
| Very Low |
Age ≤60, no JAK2, no thrombosis |
Observe or aspirin |
Primary Myelofibrosis (PMF)
Background
- Reactive marrow fibrosis driven by malignant megakaryocytes, leading to extramedullary hematopoiesis.
- Worst prognosis among MPNs.
Presentation
- Fatigue, weight loss, bone pain, night sweats, splenomegaly and arterial/venous thrombosis.
Evaluation
- Smear: teardrop shaped RBCs (dacrocytes), leukoerythroblastosis.
- CMP, LDH, uric acid - Bone marrow bx yields “dry tap.”
- Mutations in JAK2, CALR, or MPL are mutually exclusive.
Management
- Early transplant referral.
- Isolated anemia: Transfusions or adjuncts (danazol, androgens, thalidomide analogs).
- Isolated splenomegaly: hydroxyurea or JAK inhibitors (Ruxolitinib).
- Transfusion dependence or portal hypertension: Splenectomy.
Chronic Myelogenous Leukemia (CML)
Background
- Proliferation of mature granulocyte due to Philadelphia (Ph) chromosome: t(9;22) forming BCR: ABL1.
- Phases:
- Chronic: indolent presentation, <5% blasts.
- Accelerated: 10-19% blasts, ³20% basophilia.
- Blast: >20% blasts.
Presentation
- Fatigue, weight loss, night sweats, bleeding, splenomegaly.
Evaluation
- CBC w/ diff and peripheral smear.
- Marked leukocytosis 100,000/μL with granulocytic predominance.
- Molecular testing.
- Leukemoid reaction shows toxic granulations and Dohle bodies (unlike CML).
Management
- Get US spleen to assess size.
- Cytoreduction (Hydroxyurea).
- Tyrosine kinase inhibitors (TKI) (Imatinib, dasatinib, nilotinib), monitoring BCR:ABL PCR q3mo for response. Attn: many TKI cannot be taken with PPI – counsel the patient and choose TKI accordingly.
- Transplant in advanced or TKI-resistant disease.
