The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study.

Objectives In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type-1, 52-bp deletion, or type-2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. Methods We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. Results With 7.5 years median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (p = 0.002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (p = 0.046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs. CALR-type 2 groups but not JAK2V617F vs. CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, p = 0.04) adjusted by age. Conclusions Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.