Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis

Ayalew Tefferi, Paola Guglielmelli, Dirk R. Larson, Christy Finke, Emnet A. Wassie, Lisa Pieri, Naseema Gangat, Rajmonda Fjerza, Alem A. Belachew, Terra L. Lasho, Rhett P. Ketterling, Curtis A. Hanson, Alessandro Rambaldi, Guido Finazzi, Juergen Thiele, Tiziano Barbui, Animesh Pardanani, Alessandro M. Vannucchi

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284 Scopus citations

Abstract

Janus kinase 2 (JAK2) mutations define polycythemia vera (PV). Calreticulin (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations are specific to JAK2-unmutated essential thrombocythemia (ET) and primary myelofibrosis (PMF). We examined the effect of these mutations on long-term disease outcome. One thousand five hundred eighty-one patients from the Mayo Clinic (n = 826) and Italy (n = 755) were studied. Fifty-eight percent of Mayo patients were followed until death; median survivals were 19.8 years in ET (n = 292), 13.5 PV (n = 267; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.4-2.2), and 5.9 PMF (n = 267; HR, 4.5; 95% CI, 3.5-5.7). The survival advantage of ET over PV was not affected by JAK2/CALR/MPL mutational status. Survival in ET was inferior to the age- and sex-matched US population (P < .001). In PMF (n = 428), but not in ET (n = 576), survival and blast transformation (BT) were significantly affected by mutational status; outcome was best in CALR-mutated and worst in triple-negative patients: median survival, 16 vs 2.3 years (HR, 5.1; 95% CI, 3.2-8.0) and BT, 6.5% vs 25% (HR, 7.6; 95% CI, 2.8-20.2), respectively. We conclude that life expectancy in morphologically defined ET is significantly reduced but remains superior to that of PV, regardless of mutational status. In PMF, JAK2/CALR/MPL mutational status is prognostically informative.

Original languageEnglish (US)
Pages (from-to)2507-2513
Number of pages7
JournalBlood
Volume124
Issue number16
DOIs
StatePublished - Oct 16 2014

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Tefferi, A., Guglielmelli, P., Larson, D. R., Finke, C., Wassie, E. A., Pieri, L., Gangat, N., Fjerza, R., Belachew, A. A., Lasho, T. L., Ketterling, R. P., Hanson, C. A., Rambaldi, A., Finazzi, G., Thiele, J., Barbui, T., Pardanani, A., & Vannucchi, A. M. (2014). Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood, 124(16), 2507-2513. https://doi.org/10.1182/blood-2014-05-579136