Disease‑Specific Prognostic Scoring in Myeloproliferative Neoplasms

General Principle

Disease‑specific prognostic scoring systems should be employed for each myeloproliferative neoplasm (MPN) 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

At diagnosis, the International Prognostic Scoring System (IPSS) is used; during follow‑up, the Dynamic IPSS (DIPSS) or DIPSS‑Plus should be applied to reflect disease evolution. 2
The IPSS incorporates five adverse 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 independent risk factors to DIPSS: unfavorable cytogenetics, red‑cell transfusion dependence, and platelet count < 100 × 10⁹/L. 1
Molecular risk stratification is essential: patients who are CALR‑positive/ASXL1‑negative have the longest median survival (≈10 years), whereas CALR‑negative/ASXL1‑positive patients have the shortest median survival (≈2 years). 1
ASXL1 mutation testing is mandatory for all intermediate‑1 risk patients because the mutation independently worsens prognosis and may shift management toward allogeneic stem‑cell transplantation. 3
Patients with an expected median survival < 5 years (intermediate‑2 or high‑risk by DIPSS‑Plus, transfusion‑dependent, or with unfavorable cytogenetics) should be evaluated for allogeneic hematopoietic stem‑cell transplantation, the only curative option. 3

Risk stratification is based on age and history of thrombosis, defining two categories: low‑risk (age < 60 years and no prior thrombosis) and high‑risk (age ≥ 60 years or prior thrombosis). 2
High‑risk patients require phlebotomy to keep hematocrit < 45 %, low‑dose aspirin (≈80–100 mg daily), and cytoreductive therapy with hydroxyurea or interferon‑α. 2
Low‑risk patients receive phlebotomy and low‑dose aspirin only, with observation for disease progression. 2
An elevated leukocyte count is emerging as an additional thrombosis risk factor, although an intermediate‑risk category that incorporates leukocytosis has not yet been formally validated. 1

The IPSET‑thrombosis scoring system should be used; it incorporates age, prior thrombosis, cardiovascular risk factors, and JAK2V617F mutation status. 1
Scoring points: age ≥ 60 years (1 point), prior thrombosis (2 points), JAK2V617F mutation (2 points), and cardiovascular risk factors (smoking, diabetes, hypertension, hypercholesterolemia) (1 point). 1
Risk categories derived from the total score: 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 together with low‑dose aspirin. 2
Low‑risk patients are managed with low‑dose aspirin and clinical observation without cytoreduction. 2

Prognostic monitoring in CML relies on quantitative assessment of BCR‑ABL1 transcript levels and cytogenetic response to tyrosine‑kinase inhibitors, rather than traditional prognostic scores. 6
Chromosome analysis should be performed at 3, 6, and 12 months after therapy initiation (and thereafter until a complete cytogenetic response is achieved), evaluating at least 20 metaphases per sample. 6
Once a complete cytogenetic response is documented, monitoring may shift to fluorescence in‑situ hybridisation (FISH) or quantitative PCR using the International Scale for BCR‑ABL1. 6

Do not apply myelodysplastic syndrome (MDS) scoring systems to chronic myelomonocytic leukemia (CMML); instead, use CMML‑specific models such as MDAPS or MDAPS‑M1. 7
Do not omit a bone‑marrow biopsy in the diagnostic work‑up of suspected MPNs, except in polycythemia vera patients whose hemoglobin exceeds disease‑specific thresholds (≈18.5 g/dL in males, ≈16.5 g/dL in females). 1
Do not skip driver‑mutation screening (JAK2V617F, CALR, MPL) in any suspected Philadelphia‑negative MPN; the recommended sequence is JAK2V617F first, followed by CALR and MPL in ET/MF, or JAK2 exon 12 testing in JAK2V617F‑negative PV. 1
Do not initiate JAK‑inhibitor therapy in asymptomatic low‑risk myelofibrosis patients, as these agents are palliative and have not demonstrated disease‑modifying benefits. 3
Iron‑deficiency anemia can mask polycythemia vera by lowering hemoglobin while the red‑cell mass remains elevated; therefore, assess iron studies and mean corpuscular volume when PV is suspected. 5