Myeloproliferative Neoplasms (MPN): Key Information for Patients

Based on NCCN Guidelines for Patients® — Myeloproliferative Neoplasms, 2024 (NCCN Clinical Practice Guidelines in Oncology, Version 1.2024 — December 21, 2023)

What Are MPNs

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which the bone marrow produces too many blood cells. The three classic MPNs are:

Polycythemia vera (PV) — excess red blood cells
Essential thrombocythemia (ET) — excess platelets
Primary myelofibrosis (PMF) — excess megakaryocytes triggering bone marrow scarring (fibrosis)

MPNs are chronic, slow-growing cancers. They are not typically cured with standard treatment, but most people live for many years — often with a near-normal lifespan — with proper care. However, symptoms can be severe and significantly impact quality of life even in PV and ET.

MPNs are not the same as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or CML. CML is sometimes classified as an MPN but is treated separately based on the BCR::ABL1 gene.

Possible complications of all MPNs:

Abnormal bleeding (hemorrhage)
Blood clots (thrombosis)
Disease progression — ET/PV can progress to myelofibrosis; rarely, any MPN can transform to AML (called MPN blast phase, MPN-BP)

Symptoms

Most people with MPNs have symptoms. These fall into three groups:

Microvascular symptoms (caused by sluggish blood flow in small vessels):

Headaches, blurred vision, dizziness
Erythromelalgia (burning pain, redness, warmth in extremities) — characteristic of PV
Numbness and tingling in hands/feet, tinnitus (high-pitched ringing) — common in ET

Splenomegaly symptoms (enlarged spleen making blood cells):

Early satiety (feeling full quickly)
Abdominal pain or discomfort
Shortness of breath, cough

Constitutional symptoms (systemic cytokine excess):

Fatigue — the most common and debilitating MPN symptom
Night sweats, fever, weight loss
Bone pain, itchy skin (pruritus — often triggered by water contact)
Poor concentration

Symptom assessment: The MPN-10 (MPN Symptom Assessment Form Total Symptom Score) is a validated 10-item survey used in clinical practice to identify and track symptom burden over time. Available at thehematologist.org/mpn-total-symptom-score.

Diagnostic Workup

Blood tests:

CBC with differential: elevated red cells (PV), platelets (ET), or abnormal counts (PMF); may show anemia or blast cells in PMF
Blood smear: morphology assessment; presence of blasts
Comprehensive metabolic panel, liver function tests, LDH, uric acid
Erythropoietin (EPO) and iron — important for PV diagnosis (EPO is suppressed in PV)
Coagulation tests — to assess bleeding risk or acquired von Willebrand syndrome (aVWS)

Bone marrow biopsy and aspirate — required for complete diagnosis and staging (especially to assess degree of fibrosis and blast percentage).

Biomarker/molecular testing (essential):

FISH or RT-PCR for BCR::ABL1 — to exclude CML
Molecular testing for JAK2 V617F mutation (most common in all three classic MPNs)
If JAK2 V617F negative: JAK2 exon 12 mutations (if PV suspected); CALR and MPL mutations (if ET or PMF suspected)
NGS (next-generation sequencing) — can test all markers simultaneously; recommended for prognosis assessment even if single-gene testing was done first; detects high-risk mutations (ASXL1, EZH2, RAS, TP53)
Karyotype ± FISH — for cytogenetics (chromosome analysis)

About 10% of ET and PMF patients have no JAK2, CALR, or MPL mutation — called triple-negative MPN.

Diagnostic criteria:

PV: hemoglobin >16.5 g/dL (male) or >16.0 g/dL (female), or hematocrit >49% / >48%, plus bone marrow hypercellularity; JAK2 mutation (nearly universal); if no JAK2 mutation: low EPO level
ET: platelets ≥450×10⁹/L, large abnormal megakaryocytes in bone marrow, exclusion of other MPN/MDS; JAK2, CALR, or MPL mutation (not required)
PMF: abnormal megakaryocytes in bone marrow + fibrosis (overt PMF) or minimal fibrosis (pre-PMF), exclusion of other MPN/MDS; JAK2, CALR, or MPL mutation (not required); minor criteria (anemia, leukocytosis, high LDH, splenomegaly, or blasts in blood)

PV and ET: Preventing Blood Clots

In PV and ET, blood clots (thrombosis) are the leading cause of death. Preventive care is central to management.

Risk stratification:

PV: Low risk (age <60, no prior clot) vs. High risk (age ≥60 or prior clot).

ET: Uses the IPSET-thrombosis score:

Very low risk: age ≤60, no prior clot, JAK2-negative
Low risk: age ≤60, no prior clot, JAK2-positive
Intermediate risk: age >60, no prior clot, JAK2-negative
High risk: age ≥60 and/or prior clot and/or JAK2-positive

Treatment by risk level:

Low-risk PV:

Manage cardiovascular risk factors (smoking, obesity, hypertension, diabetes, inactivity)
Aspirin 80–100 mg/day
Phlebotomy to maintain hematocrit <45% (target <42% for some); performed as often as needed

High-risk PV:

All of the above, plus cytoreductive therapy:
- Ropeginterferon alfa-2b-njft (BESREMi) — preferred
- Hydroxyurea — preferred
- Peginterferon alfa-2a
- Ruxolitinib — sometimes useful

Very low-risk ET: manage cardiovascular risk factors; aspirin only if microvascular symptoms present.

Low- and intermediate-risk ET: manage cardiovascular risk factors + aspirin.

High-risk ET:

Manage cardiovascular risk factors + aspirin
Cytoreductive therapy:
- Hydroxyurea — preferred
- Peginterferon alfa-2a
- Anagrelide

Phlebotomy (PV): removes iron-laden red blood cells; reduces hematocrit; may provide rapid relief of symptoms. Avoid iron supplements during phlebotomy.

Note: Aspirin is contraindicated in very-low-risk ET patients with acquired von Willebrand syndrome (aVWS) — it may increase bleeding risk. High platelet counts can lower von Willebrand factor. Smoking blocks aspirin's antiplatelet effect.

Pregnancy: High-risk pregnancies require joint care with a high-risk obstetrician. Hydroxyurea must NOT be used during pregnancy, while trying to conceive, or while breastfeeding. Aspirin + low-molecular-weight heparin (LMWH) are standard. Interferon is an option to lower counts if needed. Hematocrit targets during pregnancy: <41% (1st trimester), <38% (2nd), <39% (3rd).

Surgery: Blood counts must be controlled before any surgery. Aspirin is stopped 1 week before surgery.

Change of treatment is needed for: new blood clot, major bleeding, aVWS, enlarging spleen, inadequate count control, new/worsening symptoms, bone marrow fibrosis, blast cells in blood.

PV and ET progression: Approximately 10% of PV/ET patients progress to myelofibrosis over time. Progression is monitored by declining need for cytoreduction and declining blood counts; confirmed by bone marrow biopsy.

Myelofibrosis: Treatment

Types:

Primary myelofibrosis (PMF) — first and only MPN; includes pre-fibrotic PMF (pre-PMF) and overt PMF
Post-PV myelofibrosis or post-ET myelofibrosis — when PV or ET progresses

Prognosis scoring: Required before treatment planning.

For PMF ≤70 years: MIPSS-70 or MIPSS70-Plus v2.0 (requires full molecular/cytogenetic testing)
For PMF, any age: DIPSS or DIPSS-Plus
For post-PV/post-ET MF: MYSEC-PM

NCCN groups all scores into two categories for treatment decisions: lower risk and higher risk.

Treatment for myelofibrosis WITHOUT anemia:

Risk level	Clinical status	Treatment
Lower	No symptoms	Watch and wait or clinical trial
Lower	With symptoms	Clinical trial; ruxolitinib, peginterferon, hydroxyurea, pacritinib (if plt <50k), momelotinib
Higher	Platelets ≥50,000	Allogeneic HCT (curative intent) or clinical trial + ruxolitinib/fedratinib/momelotinib/pacritinib
Higher	Platelets <50,000	Allogeneic HCT or clinical trial + pacritinib (preferred) or momelotinib

JAK inhibitors (oral targeted therapy):

Ruxolitinib (Jakafi) — reduces spleen size and constitutional symptoms; standard for symptomatic MF with adequate platelets
Fedratinib (INREBIC) — for MF with platelets ≥50,000 when ruxolitinib is inadequate
Pacritinib (Vonjo) — preferred for MF with severe thrombocytopenia (platelets <50,000)
Momelotinib (Ojjaara) — for MF with anemia; improves both MF symptoms and hemoglobin

Treatment for myelofibrosis WITH anemia (most patients develop anemia within 1 year):

If JAK inhibitor controlling MF symptoms but anemia persists: add luspatercept-aamt, erythropoiesis-stimulating agent, or danazol to ruxolitinib; or switch to momelotinib or pacritinib
If both MF symptoms and anemia uncontrolled: momelotinib (preferred), pacritinib, or above add-ons
If no MF symptoms but anemia: luspatercept-aamt, ESA (if EPO <500 mU/mL), danazol, momelotinib, pacritinib, lenalidomide + prednisone (for 5q deletion)
Red blood cell transfusions for symptomatic anemia

Allogeneic HCT (allo-HCT): the only potentially curative treatment for myelofibrosis. Indicated for higher-risk MF; every higher-risk patient should have a transplant evaluation. High-risk mutations (ASXL1, EZH2, RAS) support earlier transplant consideration. Not safe for everyone — requires a matched donor and specialized center.

Advanced phases (accelerated/blast phase, MPN-BP):

Blast count 10–19% = accelerated phase; ≥20% = blast phase (post-MPN AML)
Lab confirmation: karyotype ± FISH, flow cytometry, NGS for AML mutations
Treatment: clinical trial (preferred); low-intensity chemotherapy (azacitidine, decitabine ± JAK inhibitor or venetoclax); induction chemotherapy (AML-type) ± allogeneic HCT for eligible patients

Supportive Care

Bleeding: Most common in myelofibrosis. In PV/ET: assess and treat all causes (platelet dysfunction, aVWS, medication effects). In MF: platelet transfusion if platelets <10,000 m³; antifibrinolytic agents if transfusions ineffective. Plateletpheresis in ET for severe, life-threatening bleeds.

Blood clots: Treated with anticoagulants — LMWH, direct oral anticoagulants (apixaban, rivaroxaban, dabigatran, etc.), or warfarin. Duration determined by clot severity. Anticoagulants increase bleeding risk; careful monitoring required.

Itching (pruritus): Sensitive skin care (short cool showers, mild soap, moisturizer); antihistamines (cetirizine, diphenhydramine); topical steroids. If insufficient: ruxolitinib, SSRIs, narrow-band UVB, peginterferon, gabapentin, aprepitant, dupilumab.

Bone pain: NSAIDs, loratadine; ruxolitinib may stabilize bone pain; low-dose radiation for short-term relief.

Headaches/tinnitus: Low-dose aspirin; phlebotomy or ruxolitinib for PV; cytoreductive therapy. Migraine: triptans or topiramate.

Infections: Increased risk with myelofibrosis and JAK inhibitors. Recombinant (killed) zoster vaccine recommended for patients on JAK inhibitors. G-CSF or GM-CSF for low neutrophil counts (use with caution — can cause spleen rupture).

Tumor lysis syndrome (TLS): Risk with induction chemotherapy; prevented by hydration, allopurinol or rasburicase.

Iron overload: After >20 red blood cell transfusions or ferritin >2500 ng/mL — iron chelation therapy.

Key Messages for Patients

MPNs are chronic cancers that grow slowly. Most people live for many years, but symptoms can be significant and deserve active management — not just monitoring.
Know your mutation status (JAK2, CALR, MPL, and additional NGS mutations): this determines risk, prognosis, and guides treatment choices.
For PV and ET, preventing blood clots is the primary treatment goal. Regular phlebotomy (PV), aspirin, and cytoreductive therapy significantly reduce fatal complications.
Never stop cytoreductive therapy abruptly without medical guidance; stopping hydroxyurea or interferon without a plan can lead to rebound blood counts.
For myelofibrosis, JAK inhibitors reduce spleen size and symptoms but do not cure the disease. Allogeneic transplant is the only potential cure — every higher-risk patient should discuss this option.
The MPN-10 symptom survey is a useful tool to track how you feel over time and communicate symptom burden to your care team.
Seeing an MPN specialist (not just a general hematologist) makes a significant difference in outcomes. Second opinions are strongly encouraged.
Clinical trials are particularly important for MPNs — NCCN recommends considering them at every stage.

Source: NCCN Guidelines for Patients® — Myeloproliferative Neoplasms, 2024 (based on NCCN Clinical Practice Guidelines in Oncology, Version 1.2024 — December 21, 2023). National Comprehensive Cancer Network® (NCCN®).

Full original document available free of charge: NCCN.org/patientguidelines

This material is for informational purposes only and does not replace consultation with a treating physician.