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CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Prediction of thrombosis in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study on 1258 patients

Abstract

Patients with Philadelphia-negative myeloproliferative neoplasms are at high risk of thrombotic events (TEs). Predisposing factors have been identified in essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (primary MF, PMF), while yet not recognized in post PV/ET-MF (known as secondary MF, SMF). Within the 1258 SMF of the MYSEC (MYelofibrosis SECondary to PV and ET) dataset, 135 (10.7%) developed a TE at a median follow-up of 3.5 years (range, 1–21.4), with an incidence of 2.3% patients per year. Venous events accounted for two-thirds of the total. Cox multivariable analysis, supported by Fine-Gray models with death as competitive risk, showed that being on cytoreductive therapy at time of SMF evolution is associated with an absolute risk reduction of thrombosis equal to 3.3% within 3 years. Considering individually cytoreductive therapies, univariate regression model found that both conventional cytoreduction, mainly hydroxyurea, (HR 0.41, 95% CI: 0.26–0.65, p = 0.0001) and JAK inhibitors, mostly ruxolitinib, (HR 0.50, 95% CI: 0.24–1.02, p = 0.05) were associated with fewer thrombosis. Our study informs treating physicians of a non-low incidence of TEs in post PV/ET-MF and of the potential protective role of cytoreductive therapy in terms of thrombotic events.

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Fig. 1: Thrombosis-free survival.

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Data availability

The dataset analyzed during the current study is available from the corresponding author on reasonable request.

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Funding

The Varese group has been supported by grants from the Ministero della Salute, Rome, Italy [Finalizzata 2018, NET-2018–12365935, Personalized medicine program on myeloid neoplasms: characterization of the patient’s genome for clinical decision making and systematic collection of real world data to improve quality of health care]; by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca, Roma, Italy [PRIN 2017, 2017WXR7ZT; Myeloid Neoplasms: an integrated clinical, molecular and therapeutic approach]; by the charity AIL (Associazione italiana contro le leucemie-linfomi e mieloma) Onlus of Varese and by grants from Fondazione Matarelli, Milan. PG and AMV were supported by AIRC 5 × 1000 called “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEo- plasms Research Venture AIRC) and by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca, Roma, Italy [PRIN 2017, 2017WXR7ZT; Myeloid Neoplasms: an integrated clinical, molecular and therapeutic approach]. RTS was supported in part by the Cancer Research and Treatment Fund, Inc., New York, NY.

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BM and FP contributed to the conception of the work and wrote the manuscript. All Authors contributed to the acquisition of data, to revise the manuscript critically for important intellectual content, to approve the final version of the manuscript and are accountable for all aspects of the work in ensuring that questions related to the accuracy and integrity of any part have been investigated and resolved. LB was responsible for the statistical analysis.

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Mora, B., Guglielmelli, P., Kuykendall, A. et al. Prediction of thrombosis in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study on 1258 patients. Leukemia 36, 2453–2460 (2022). https://doi.org/10.1038/s41375-022-01673-3

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