Myeloproliferative Neoplasms

The answer first

Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterised by overproduction of one or more myeloid lineages: polycythaemia vera (PV) (erythrocytosis), essential thrombocythaemia (ET) (thrombocytosis), and primary myelofibrosis (PMF) (fibrosis, extramedullary haematopoiesis, cytopenias). All three share the JAK-STAT pathway activation from JAK2, CALR, or MPL mutations; JAK2 V617F is present in 95 per cent of PV, 50-60 per cent of ET, and 50-60 per cent of PMF. The FRACP candidate must defend the diagnostic criteria (WHO 2016/2022), the thrombotic risk stratification (IPSET-thrombosis for ET; IPSS-MF for PMF), the indications for ruxolitinib (symptomatic MF, symptomatic splenomegaly, high-risk PV), and the unique management of pregnancy in MPN (interferon alpha first-line). [1] [6]

The answer-first synthesis is: confirm the clonal nature of the myeloproliferation (JAK2/CALR/MPL mutation, EPO level, marrow biopsy); classify by disease entity (PV, ET, PMF); stratify thrombotic and fibrotic risk; manage by disease (phlebotomy plus low-dose aspirin for PV; cytoreduction with hydroxycarbamide or anagrelide for high-risk ET; ruxolitinib or fedratinib for symptomatic MF; allogeneic stem cell transplant for transplant-eligible high-risk MF). [2] [5]

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8. [8]Rampal RK, Grosicki S, Chraniuk D et al. Pelabresib plus ruxolitinib for JAK inhibitor-naive myelofibrosis: a randomized phase 3 trial Nature medicine, 2025.PMID 40065169
9. [9]Verstovsek S, Gerds AT, Vannucchi AM et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study Lancet (London, England), 2023.PMID 36709073
10. [10]Marchetti M, Vannucchi AM, Griesshammer M et al. Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations The Lancet. Haematology, 2022.PMID 35358444
11. [11]Wagstaff AJ, Keating GM Anagrelide: a review of its use in the management of essential thrombocythaemia Drugs, 2006.PMID 16398570