Validation of the IPSET score for thrombosis in patients with prefibrotic myelofibrosis

Paola Guglielmelli,Alessandra Carobbio,Valerio De Stefano,Mario Cazzola,Giacomo Coltro,Juergen Thiele,Alessandro Maria Vannucchi,Elisa Rumi,Giada Rotunno,Chiara Cavalloni,Silvia Betti,Tiziano Barbui,Francesco Mannelli,Lara Mannelli,Maria Chiara Finazzi

doi:10.1038/s41408-020-0289-2

Abstract

Pre-fibrotic myelofibrosis (pre-PMF) and essential thrombocythemia (ET) are characterized by similarly increased rate of thrombotic events, but no study specifically analyzed risk factors for thrombosis in pre-PMF. In a multicenter cohort of 382 pre-PMF patients collected in this study, the rate of arterial and venous thrombosis after diagnosis was 1.0 and 0.95% patients/year. Factors significantly associated with arterial thrombosis were age, leukocytosis, generic cardiovascular risk factors, JAK2V617F and high molecular risk mutations, while only history of previous thrombosis, particularly prior venous thrombosis, was predictive of venous events. The risk of total thromboses was accurately predicted by the the international prognostic score for thrombosis in essential thrombocythemia (IPSET) score, originally developed for ET, and corresponded to 0.67, 2.05, and 2.95% patients/year in the low-, intermediate-, and high-risk categories. IPSET was superior to both the conventional 2-tiered score and the revised IPSET in this cohort of pre-PMF patients. We conclude that IPSET score can be conveniently used for thrombosis risk stratification in patients with pre-PMF and might represent the basis for individualized management aimed at reducing the increased risk of major cardiovascular events. Further refinement of the IPSET score in pre-PMF might be pursued by additional, prospective studies evaluating the inclusion of leukocytosis and/or adverse mutational profile as novel variables.

Highlights

Introduction The revised2016 World Health Organization (WHO)classification of myeloproliferative neoplasms recognized prefibrotic myelofibrosis as an entity distinct from essential thrombocythemia (ET)1–3
Patients with prefibrotic myelofibrosis are at about twofold increased risk of cardiovascular events, including major thrombosis and hemorrhage, compared with the reference age-matched population, a figure that is substantially similar to patients with ET
Since in ET thrombosis represents the main cause of mortality, scores have been developed over time to predict the individual risk of thrombosis and facilitate the adoption of the most appropriate therapeutic measures

Summary

Introduction

Introduction The revised2016 World Health Organization (WHO)classification of myeloproliferative neoplasms recognized prefibrotic myelofibrosis (pre-PMF) as an entity distinct from essential thrombocythemia (ET). Patients with pre-PMF have higher leukocyte and platelet counts, lower hemoglobin, higher lactate dehydrogenase levels, and more frequently splenomegaly compared with patients with ET4. 661 patients with pre-PMF, the median overall survival (OS) of pre-PMF was 14.7 years, significantly shorter than 30.2 years in a parallel cohort of 421 unselected patients with ET, accounting for a hazard ratio (HR) of 2.7 (95% confidence interval (CI), 1.9–3.7). ET and pre-PMF have comparable risk of cardiovascular events. In one study that considered 180 patients with pre-PMF, the cumulative risk of thrombotic complications was 25.4% compared with 21.5% in 891 ET patients, accounting for a rate of overall major thrombosis of 1.9 and 1.7% patients/year, respectivey. In another study on 109 pre-PMF patients, the 10-year cumulative incidence of thrombosis was 18.5% (95%CI, 10.7–27.8) compared with 18% (95%CI, 0.4–6.0) in 269 patients with ET7

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Conclusion