Abstract

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts 3%, and to CALR-unmutated genotype, 1 point to platelet count <150 × 109/l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival (P<0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2–7.9; 126 patients), and high risk (2 years, 95% CI: 1.7–3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.

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Acknowledgements

This work was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC; Milano, Italy), Special Program Molecular Clinical Oncology 5 × 1000 to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) project #1005. A complete list of AGIMM investigators is available at http://www.progettoagimm.it. P.G. also received funding by AIRC IG2014-15967 and by the Ministero della Salute (project code GR-2011-02352109). The Varese group was also supported by grants from the Fondazione Matarelli (Milano, Italy), Fondazione Rusconi (Varese, Italy) and AIL Varese ONLUS. MC and FP were supported by a grant from the Fondazione Regionale Ricerca Biomedica (FRRB), Regione Lombardia. RTS was supported in part by the Cancer Research and Treatment Fund, Inc., New York, NY.

Author information

Author notes

    • F Passamonti
    •  & T Giorgino

    co-senior authors.

    • M Cazzola
    •  & A M Vannucchi

    These authors contributed equally to this work.

Affiliations

  1. Hematology, Department of Medicine and Surgery, University of Insubria, Ospedale di Circolo, ASST Sette Laghi, Varese, Italy

    • F Passamonti
    • , B Mora
    • , M Maffioli
    • , D Caramazza
    •  & M Merli
  2. Institute of Neurosciences, National Research Council of Italy, Padova, Italy

    • T Giorgino
  3. CRIMM-Centro Ricerca e Innovazione delle Malattie Mieloproliferative, Department of Experimental and Clinical Medicine, Azienda ospedaliera-Universitaria Careggi, University of Florence, Florence, Italy

    • P Guglielmelli
    • , G Rotunno
    •  & A M Vannucchi
  4. Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy

    • E Rumi
    • , D Pietra
    •  & M Cazzola
  5. Department of Oncology-Hematology, University of Milan and BMT Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

    • A Rambaldi
  6. Ospedale Niguarda Cà Granda, Milano, Italy

    • M Caramella
  7. Moffit Cancer Center, Tampa, FL, USA

    • R Komrokji
  8. Stanford University, Palo Alto, CA, USA

    • J Gotlib
  9. Hôpital Saint-Louis et Université Paris Diderot, Paris, France

    • J J Kiladjian
  10. Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

    • F Cervantes
  11. Department of Hematology, University Hospitals Leuven and Laboratory of Experimental Transplantation, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium

    • T Devos
  12. Policlinico S. Orsola-Malpighi, Bologna, Italy

    • F Palandri
  13. Università Cattolica del Sacro Cuore, Roma, Italy

    • V De Stefano
  14. Ospedale S. Bortolo, Vicenza, Italy

    • M Ruggeri
  15. Weill Cornell Medical College, NY, USA

    • R T Silver
  16. SC Hematology, A.O. Città della Salute e della Scienza, Turin, Italy

    • G Benevolo
  17. Università di Bari, Bari, Italy

    • F Albano
  18. Cytogenetics and Medical Genetics Laboratory, Ospedale di Circolo, ASST Sette Laghi, Varese, Italy

    • R Casalone
  19. FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy

    • T Barbui

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The authors declare no conflict of interest.

Corresponding author

Correspondence to F Passamonti.

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DOI

https://doi.org/10.1038/leu.2017.169

Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu)

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