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CHRONIC MYELOPROLIFERATIVE NEOPLASMS

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

Leukemia volume 36, pages 2453–2460 (2022)Cite this article

Subjects

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.

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.

Author information

Authors and Affiliations

  1. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Barbara Mora, Lorenza Bertù & Francesco Passamonti

  2. Center of Research and Innovation of Myeloproliferative Neoplasms, University of Florence, Florence, Italy

    Paola Guglielmelli, Giada Rotunno & Alessandro M. Vannucchi

  3. Malignant Hematology Department, Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Andrew Kuykendall & Rami S. Komrokji

  4. Hematology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Elisa Rumi, Ilaria C. Casetti & Luca Arcaini

  5. Hematology, Ospedale di Circolo, ASST Sette Laghi, Varese, Italy

    Margherita Maffioli, Michele Merli, Marco Brociner & Domenica Caramazza

  6. Institute of Hematology, Azienda Ospedaliero-Universitaria S.Orsola-Malpighi di Bologna, Bologna, Italy

    Francesca Palandri & Giuseppe Auteri

  7. Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

    Valerio De Stefano

  8. Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Marianna Caramella

  9. FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy

    Silvia Salmoiraghi & Tiziano Barbui

  10. Centre d’Investigations Cliniques, Hôpital Saint-Louis et Université Paris Diderot, Paris, France

    Jean-Jacques Kiladjian

  11. Division of Hematology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

    Jason Gotlib

  12. UOC Ematologia, Foundation IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy

    Alessandra Iurlo & Daniele Cattaneo

  13. Hematology Department, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain

    Francisco Cervantes

  14. Hematology Department, San Bortolo Hospital, Vicenza, Italy

    Marco Ruggeri

  15. Richard T. Silver Myeloproliferative Neoplasms Center, Weill Cornell Medical Center, New York, NY, USA

    Richard T. Silver

  16. Hematology - Dept. of Emergency and Organ Transplantation, University of Bari, Bari, Italy

    Francesco Albano

  17. Hematology, AOU Città della Salute e della Scienza di Torino, Turin, Italy

    Giulia Benevolo

  18. Haematology Directorate, SA Pathology, Royal Adelaide Hospital and Flinders Medical Centre, Adelaide, South Australia

    David M. Ross

  19. IRCCS Humanitas Clinical and Research Center, Rozzano, Italy

    Matteo G. Della Porta

  20. Department of Hematology, University Hospitals Leuven and Department of Microbiology and Immunology, Laboratory of Molecular Immunology (Rega Institute), Ku Leuven, Leuven, Belgium

    Timothy Devos

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  1. Barbara Mora
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  2. Paola Guglielmelli
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  10. Jean-Jacques Kiladjian
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  14. Marco Ruggeri
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  15. Richard T. Silver
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  19. Matteo G. Della Porta
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  20. Timothy Devos
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  21. Giada Rotunno
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  22. Rami S. Komrokji
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  23. Ilaria C. Casetti
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  24. Michele Merli
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  25. Marco Brociner
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  28. Tiziano Barbui
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  29. Daniele Cattaneo
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  30. Lorenza Bertù
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  32. Alessandro M. Vannucchi
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  33. Francesco Passamonti
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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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Correspondence to Francesco Passamonti.

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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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