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. 2014 Oct 16;124(16):2507-13; quiz 2615.
doi: 10.1182/blood-2014-05-579136. Epub 2014 Jul 18.

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

Ayalew Tefferi  1 , Paola Guglielmelli  2 , Dirk R Larson  3 , Christy Finke  1 , Emnet A Wassie  1 , Lisa Pieri  2 , Naseema Gangat  1 , Rajmonda Fjerza  2 , Alem A Belachew  1 , Terra L Lasho  1 , Rhett P Ketterling  4 , Curtis A Hanson  5 , Alessandro Rambaldi  6 , Guido Finazzi  6 , Juergen Thiele  7 , Tiziano Barbui  6 , Animesh Pardanani  1 , Alessandro M Vannucchi  2
Affiliations

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

Ayalew Tefferi et al. Blood. .

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.

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Figures

Figure 1
Figure 1
Comparison of survival in 826 Mayo Clinic patients with ET vs PV vs PMF. Survival in ET was also compared with the age- and sex-matched US population.
Figure 2
Figure 2
Comparison of BT rates among 826 Mayo Clinic patients with ET vs PV vs PMF, which includes accounting for death as a competing risk. Cumulative incidences of BT (95% CI) were 0.038 (0.013-0.062) for ET, 0.068 (0.033-0.102) for PV, and 0.142 (0.095-0.186) for PMF; P values were .03 for PV vs PMF at 20 years, .002 for ET vs PMF at 20 years, and .16 for ET vs PV at 20 years.
Figure 3
Figure 3
Survival data comparisons in Mayo Clinic patients with PV vs JAK2- or CALR-mutated ET or PMF. P values were <.01 for (1) JAK2-mutated PMF vs CALR-mutated PMF, PV, JAK2-mutated ET or CALR-mutated ET, (2) CALR-mutated PMF vs CALR-mutated ET or JAK2-mutated ET, and (3) PV vs JAK2-mutated or CALR-mutated ET. Univariate analysis did not show a difference between JAK2 and CALR-mutated ET (P = .28) or CALR-mutated PMF and PV (P = .54).
Figure 4
Figure 4
Comparison of survival among 428 patients with PMF stratified by their mutational status.
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Comment in

References

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