Is there a single myeloproliferative disease score, or should I use disease‑specific prognostic scoring systems for primary myelofibrosis, essential thrombocythemia, polycythemia vera, and chronic myeloid leukemia?

Myeloproliferative Disease Prognostic Scoring

You should use disease-specific prognostic scoring systems for each myeloproliferative neoplasm subtype rather than a single unified score, because each disease has distinct clinical outcomes, risk factors, and therapeutic implications that require tailored risk stratification. 1, 2

Disease-Specific Scoring Systems

Primary Myelofibrosis (PMF)

Use the International Prognostic Scoring System (IPSS) at diagnosis and Dynamic IPSS (DIPSS) or DIPSS-Plus during disease course. 1

• IPSS incorporates five adverse prognostic factors: age >65 years, constitutional symptoms, hemoglobin <10 g/dL, white blood cell count >25 × 10⁹/L, and peripheral blood blasts ≥1%. 1

• DIPSS-Plus adds three additional independent risk factors to DIPSS: unfavorable karyotype, red cell transfusion dependency, and platelet count <100 × 10⁹/L. 1, 3

• Molecular risk stratification is critical: CALR-positive/ASXL1-negative patients have the longest survival (median 10.4 years), while CALR-negative/ASXL1-positive patients have the shortest (median 2.3 years). 1, 3

• ASXL1 mutation testing is mandatory for all intermediate-1 risk patients because it independently worsens prognosis and may shift management toward allogeneic stem cell transplantation. 3

• Patients with median survival <5 years (intermediate-2 or high-risk by DIPSS-Plus, transfusion-dependent, or unfavorable cytogenetics) should be evaluated for allogeneic HSCT, the only curative therapy. 3

Polycythemia Vera (PV)

Risk stratification is based on age and thrombosis history, creating two categories: low-risk (age <60 years and no prior thrombosis) versus high-risk (age ≥60 years or prior thrombosis). 1

• High-risk patients require phlebotomy to maintain hematocrit <45%, low-dose aspirin (81-100 mg daily), and cytoreductive therapy with hydroxyurea or interferon-α. 1, 4

• Low-risk patients receive phlebotomy and low-dose aspirin only, with observation for disease progression. 1, 4

• Leukocyte count is emerging as an additional thrombosis risk factor, though an intermediate-risk category incorporating leukocytosis has not been formally validated. 1

Essential Thrombocythemia (ET)

Use the IPSET-thrombosis scoring system, which incorporates age, prior thrombosis, cardiovascular risk factors, and JAK2V617F mutation status. 1, 5

• IPSET-thrombosis scoring: age ≥60 years (1 point), prior thrombosis (2 points), JAK2V617F mutation (2 points), cardiovascular risk factors including smoking, diabetes, hypertension, or hypercholesterolemia (1 point). 1, 5

• Risk categories: low risk (0-1 points), intermediate risk (2 points), high risk (≥3 points). 5

• High-risk patients (age ≥60 years or prior thrombosis) require cytoreductive therapy with hydroxyurea or interferon-α plus low-dose aspirin. 1, 5

• Low-risk patients receive low-dose aspirin and observation without cytoreduction. 1, 5

Chronic Myeloid Leukemia (CML)

CML uses distinct molecular monitoring rather than traditional prognostic scores, focusing on BCR-ABL1 transcript levels and cytogenetic response to tyrosine kinase inhibitors. 1

• Follow-up chromosome analysis should be performed at 3,6, and 12 months post-treatment until complete cytogenetic response is achieved, analyzing at least 20 cells. 1

• Once complete cytogenetic response is achieved, monitoring can transition to FISH or quantitative PCR using the International Scale. 1

Critical Pitfalls to Avoid

• Do not use myelodysplastic syndrome (MDS) scoring systems for chronic myelomonocytic leukemia (CMML), which requires disease-specific prognostic models like MDAPS or MDAPS-M1. 1

• Do not omit bone marrow biopsy in suspected MPN cases, as it is necessary for diagnosis except in PV patients with hemoglobin >18.5 g/dL (males) or >16.5 g/dL (females). 1

• Do not skip driver mutation screening (JAK2V617F, CALR, MPL) in all suspected Ph-negative MPNs; test JAK2V617F first, then CALR and MPL in ET/MF, or JAK2 exon 12 in JAK2V617F-negative PV. 1

• Do not initiate JAK inhibitors in asymptomatic low-risk myelofibrosis patients, as these agents are palliative and have not demonstrated disease-modifying effects. 3

• Iron deficiency can mask PV by lowering hemoglobin below diagnostic thresholds while maintaining elevated red cell mass; check iron studies and MCV. 5