Mutations and thrombosis in essential thrombocythemia: prognostic interaction with age and thrombosis history

BackgroundVascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations. ObjectivesTo examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis-free survival in ET. Patients and MethodsAnalysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients. ResultsAmong 300 Mayo patients with ET (median age 55yr, 60% females), mutational frequencies were 53% JAK2, 32% CALR, 3% MPL, and 12% JAK2, CALR and MPL wild type. One hundred and six (35%) patients experienced arterial (n=75) or venous (n=43) events, before (n=55) or after (n=71) diagnosis. In univariate analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31, 95% CI 0.11-0.86), and CALR-mutated (0.53, 95% CI 0.30-0.92) patients displayed better thrombosis-free survival. JAK2, CALR, and MPL wild type remained significant (P=0.03; HR 0.32, 95% CI 0.11-0.9) during multivariable analysis that included age (P=0.01) and thrombosis history (P=0.0006); a favorable impact from CALR mutations was of borderline significance (P=0.1; HR 0.62, 95% CI 0.35-1.1), but became significant (P=0.02) when multivariable analysis including thrombosis history (P=0.02) was performed on patients younger than 60yr of age. ConclusionsThe favorable impact of mutational status on thrombosis-free survival in ET might be most evident for JAK2, CALR, and MPL wild type patients, whereas the favorable effect from CALR mutations might be confined to young patients.