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.
Subscribe to Journal
Get full journal access for 1 year
only $33.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–2405.
Passamonti F, Maffioli M . Update from the latest WHO classification of MPNs: a user's manual. Hematol Am Soc Hematol Educ Program 2016; 2016: 534–542.
Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 2008; 22: 437–438.
Passamonti F, Rumi E, Arcaini L, Castagnola C, Lunghi M, Bernasconi P et al. Leukemic transformation of polycythemia vera: a single center study of 23 patients. Cancer 2005; 104: 1032–1036.
Passamonti F, Rumi E, Caramella M, Elena C, Arcaini L, Boveri E et al. A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis. Blood 2008; 111: 3383–3387.
Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113: 2895–2901.
Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S et al. 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: 392–397.
Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A et al. 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: 1703–1708.
Hernandez-Boluda JC, Pereira A, Gomez M, Boque C, Ferrer-Marin F, Raya JM et al. 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: e55–e57.
Gowin K, Coakley M, Kosiorek H, Mesa R . Discrepancies of applying primary myelofibrosis prognostic scores for patients with post polycythemia vera/ essential thrombocytosis myelofibrosis. Haematologica 2016; 101: e405–e406.
Chen M, Xu ZF, Xu JQ, Li B, Zhang PH, Qin TJ et al. Analysis of prognostic factors in Chinese patients with post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Zhonghua Xue Ye Xue Za Zhi 2016; 37: 876–880.
Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013; 27: 1861–1869.
Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 2014; 28: 1472–1477.
Wassie E, Finke C, Gangat N, Lasho TL, Pardanani A, Hanson CA et al. A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients. Br J Haematol 2015; 169: 71–76.
Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood 2014; 124: 1062–1069.
Rozovski U, Verstovsek S, Manshouri T, Dembitz V, Bozinovic K, Newberry K et al. An accurate, simple prognostic model consisting of age, JAK2, CALR, and MPL mutation status for patients with primary myelofibrosis. Haematologica 2017; 102: 79–84.
Passamonti F, Mora B, Giorgino T, Guglielmelli P, Cazzola M, Maffioli M et al. Driver mutations' effect in secondary myelofibrosis: an international multicenter study based on 781 patients. Leukemia 2016.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937–951.
Pavlou M, Ambler G, Seaman SR, Guttmann O, Elliott P, King M et al. How to develop a more accurate risk prediction model when there are few events. BMJ 2015; 351: h3868.
Friedman J, Hastie T, Tibshirani R . Regularization paths for generalized linear models via coordinate descent. J Stat Softw 2010; 33: 1–22.
Grambsch PM, Therneau TM . Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994; 81: 515–526.
Rotunno G, Pacilli A, Artusi V, Rumi E, Maffioli M, Delaini F et al. Epidemiology and clinical relevance of mutations in post-polycythemia vera and post-essential thrombocythemia myelofibrosis. A study on 359 patients of the AGIMM group. Am J Hematol 2016; 91: 681–686.
Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011; 29: 761–770.
Mesa RA, Passamonti F . Individualizing care for patients with myeloproliferative neoplasms: integrating genetics, evolving therapies, and patient-specific disease burden. Am Soc Clin Oncol Educ Book 2016; 35: e324–e335.
Passamonti F, Maffioli M, Cervantes F, Vannucchi AM, Morra E, Barbui T et al. Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts. Blood 2014; 123: 1833–1835.
Barosi G, Zhang MJ, Peter Gale R . Does ruxolitinib improve survival of persons with MPN-associated myelofibrosis? Should it? Leukemia 2014; 28: 2267–2270.
Passamonti F, Vannucchi AM, Cervantes F, Harrison C, Morra E, Kantarjian H et al. Ruxolitinib and survival improvement in patients with myelofibrosis. Leukemia 2015; 29: 739–740.
Cervantes F, Pereira A . Does ruxolitinib prolong the survival of patients with myelofibrosis? Blood 2017; 129: 832–837.
Kroger N, Giorgino T, Scott BL, Ditschkowski M, Alchalby H, Cervantes F et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood 2015; 125: 3347–3350.
Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A et al. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia 2013; 27: 1322–1327.
Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366: 799–807.
Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012; 366: 787–798.
Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol 2015; 1: 643–651.
Tefferi A, Al-Ali HK, Barosi G, Devos T, Gisslinger H, Jiang Q et al. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia 2017; 31: 896–902.
Alchalby H, Yunus DR, Zabelina T, Kobbe G, Holler E, Bornhauser M et al. Risk models predicting survival after reduced-intensity transplantation for myelofibrosis. Br J Haematol 2012; 157: 75–85.
Marty C, Lacout C, Droin N, Le Couedic JP, Ribrag V, Solary E et al. A role for reactive oxygen species in JAK2(V617F) myeloproliferative neoplasm progression. Leukemia 2013; 27: 2187–2195.
Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG et al. Age-related clonal hematopoiesis associated with adverse outcomes. New Engl J Med 2014; 371: 2488–2498.
Vainchenker W, Constantinescu SN, Plo I . Recent advances in understanding myelofibrosis and essential thrombocythemia. F1000Res 2016; 5: F1000.
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.
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on the Leukemia website
About this article
Cite this article
Passamonti, F., Giorgino, T., Mora, B. et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia 31, 2726–2731 (2017). https://doi.org/10.1038/leu.2017.169
European wide survey on allogeneic haematopoietic cell transplantation practice for myelofibrosis on behalf of the EBMT chronic malignancies working party
Current Research in Translational Medicine (2021)
International Journal of Hematology (2021)
Improving symptom burden and quality of life in patients with myelofibrosis: current strategies and future directions
Expert Review of Hematology (2021)
Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival