A Practical Guide for Using Myelofibrosis Prognostic Models in the Clinic

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  • 1 Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School;
  • 2 Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School; and
  • 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
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Primary myelofibrosis (PMF) has the least favorable prognosis of the Philadelphia chromosome–negative myeloproliferative neoplasms, which also include essential thrombocythemia (ET) and polycythemia vera (PV). However, clinical presentations and outcomes of PMF vary widely, with median overall survival ranging from years to decades. Given the heterogeneity of PMF, there has been considerable effort to develop discriminatory prognostic models to help with management decisions, particularly for the consideration of hematopoietic stem cell transplantation in patients at higher risk. Although earlier models incorporated only clinical features in risk stratification, contemporary models increasingly use molecular and cytogenetic features, leading to more comprehensive prognostication. This article reviews the most widely adopted prognostic models used for PMF, including the International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS)/DIPSS+, mutation-enhanced IPSS for transplant-age patients (MIPSS70)/MIPSS70+/MIPSS70+ version 2.0, genetically inspired prognostic scoring system, and Myelofibrosis Secondary to PV and ET-Prognostic Model in patients with post-ET/PV myelofibrosis. We also discuss newly emerging prognostic models and provide a practical approach to risk stratification in patients with PMF and post-ET/PV myelofibrosis.

Submitted December 23, 2019; accepted for publication March 4, 2020.

Disclosures: Dr. How has disclosed that she has no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Dr. Hobbs has disclosed that she receives grant/research support from Bayer, Incyte, and Merck; consulting fees from Incyte, Celgene, Agios, and Jazz Pharmaceuticals; and is a scientific advisor for Novartis, Celgene, Bristol-Myers Squibb, and Jazz Pharmaceuticals.

Correspondence: Gabriela Hobbs, MD, Massachusetts General Hospital, Department of Medical Oncology, Zero Emerson, Office 138, 55 Fruit Street, Boston, MA 02114. Email: ghobbs@partners.org
  • 1.

    Tefferi A, Guglielmelli P, Larson DR, . Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood 2014;124:25072513.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Cervantes F, Dupriez B, Pereira A, . New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009;113:28952901.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Dupriez B, Morel P, Demory JL, . Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 1996;88:10131018.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Cervantes F, Barosi G, Demory JL, . Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol 1998;102:684690.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Cervantes F, Pereira A, Esteve J, . Identification of “short-lived” and “long-lived” patients at presentation of idiopathic myelofibrosis. Br J Haematol 1997;97:635640.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Reilly JT, Snowden JA, Spearing RL, . Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases. Br J Haematol 1997;98:96102.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Kvasnicka HM, Thiele J, Werden C, . Prognostic factors in idiopathic (primary) osteomyelofibrosis. Cancer 1997;80:708719.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Elliott MA, Verstovsek S, Dingli D, . Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis. Leuk Res 2007;31:15031509.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Passamonti F, Cervantes F, Vannucchi AM, . A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010;115:17031708.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Passamonti F, Cervantes F, Vannucchi AM, . Dynamic international prognostic scoring system (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood 2010;116:28572858.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Tefferi A, Siragusa S, Hussein K, . Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype. Am J Hematol 2010;85:1417.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Hussein K, Pardanani AD, Van Dyke DL, . International Prognostic Scoring System—independent cytogenetic risk categorization in primary myelofibrosis. Blood 2010;115:496499.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Caramazza D, Begna KH, Gangat N, . Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia 2011;25:8288.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Patnaik MM, Caramazza D, Gangat N, . Age and platelet count are IPSS-independent prognostic factors in young patients with primary myelofibrosis and complement IPSS in predicting very long or very short survival. Eur J Haematol 2010;84:105108.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Gangat N, Caramazza D, Vaidya R, . DIPSS plus: a refined dynamic international prognostic scoring system for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011;29:392397.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Gerds AT, Gotlib J, Bose P, . NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms. Version 1.2020. Accessed July 27, 2020. To view the most recent version, visit NCCN.org

  • 17.

    Kröger NM, Deeg JH, Olavarria E, . Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia 2015;29:21262133.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Baxter EJ, Scott LM, Campbell PJ, . Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:10541061.

  • 19.

    Vainchenker W, Delhommeau F, Constantinescu SN, . New mutations and pathogenesis of myeloproliferative neoplasms. Blood 2011;118:17231735.

  • 20.

    Guglielmelli P, Lasho TL, Rotunno G, . MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. J Clin Oncol 2018;36:310318.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Tefferi A, Guglielmelli P, Lasho TL, . MIPSS70+ version 2.0: mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis. J Clin Oncol 2018;36:17691770.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Arber DA, Orazi A, Hasserjian R, . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:23912405.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Tefferi A, Nicolosi M, Mudireddy M, . Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients. Leukemia 2018;32:11891199.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Tefferi A, Finke CM, Lasho TL, . U2AF1 mutation types in primary myelofibrosis: phenotypic and prognostic distinctions. Leukemia 2018;32:22742278.

  • 25.

    Tefferi A, Guglielmelli P, Nicolosi M, . GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia 2018;32:16311642.

  • 26.

    Hernández-Boluda JC, Pereira A, Gómez M, . The International Prognostic Scoring System does not accurately discriminate different risk categories in patients with post-essential thrombocythemia and post-polycythemia vera myelofibrosis. Haematologica 2014;99:e5557.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Masarova L, Bose P, Daver N, . Patients with post-essential thrombocythemia and post-polycythemia vera differ from patients with primary myelofibrosis. Leuk Res 2017;59:110116.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Tefferi A, Saeed L, Hanson CA, . Application of current prognostic models for primary myelofibrosis in the setting of post-polycythemia vera or post-essential thrombocythemia myelofibrosis. Leukemia 2017;31:28512852.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Passamonti F, Giorgino T, Mora B, . A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia 2017;31:27262731.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Hernández-Boluda JC, Pereira A, Correa JG, . Performance of the myelofibrosis secondary to PV and ET-prognostic model (MYSEC-PM) in a series of 262 patients from the Spanish registry of myelofibrosis. Leukemia 2018;32:553555.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Palandri F, Palumbo GA, Iurlo A, . Differences in presenting features, outcome and prognostic models in patients with primary myelofibrosis and post-polycythemia vera and/or post-essential thrombocythemia myelofibrosis treated with ruxolitinib. New perspective of the MYSEC-PM in a large multicenter study. Semin Hematol 2018;55:248255.

    • Search Google Scholar
    • Export Citation
  • 32.

    Masarova L, Kantarjian H, Verstovsek S. Validation of the myelofibrosis secondary to PV and prognostic model in newly diagnosed patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis: MD Anderson Cancer Center. Clin Lymphoma Myeloma Leuk 2017;17(Suppl):S2021.

    • Search Google Scholar
    • Export Citation
  • 33.

    Grinfeld J, Nangalia J, Baxter EJ, . Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med 2018;379:14161430.

  • 34.

    Gagelmann N, Ditschkowski M, Bogdanov R, . Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood 2019;133:22332242.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Kröger N, Giorgino T, Scott BL, . Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood 2015;125:33473350.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Ali H, Aldoss I, Yang D, . MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen. Blood Adv 2019;3:8395.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Rotunno G, Pacilli A, Artusi V, . Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: a study on 359 patients of the AGIMM group. Am J Hematol 2016;91:681686.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Scott BL, Gooley TA, Sorror ML, . The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood 2012;119:26572664.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Barbui T, Thiele J, Passamonti F, . Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011;29:31793184.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Rumi E, Boveri E, Bellini M, . Clinical course and outcome of essential thrombocythemia and prefibrotic myelofibrosis according to the revised WHO 2016 diagnostic criteria. Oncotarget 2017;8:101735101744.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Guglielmelli P, Pacilli A, Rotunno G, . Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis. Blood 2017;129:32273236.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Mudireddy M, Shah S, Lasho T, . Prefibrotic versus overtly fibrotic primary myelofibrosis: clinical, cytogenetic, molecular and prognostic comparisons. Br J Haematol 2018;182:594597.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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