PB0933 - Somatic CALR1 vs. CALR2 mutation in Patients with Essential Thrombocythemia and the Risk of Thrombosis. A systemic review and meta-analysis.

Background: Calreticulin (CALR) gene mutation is the most common mutation in patients with Janus Kinase 2(JAK2) negative essential thrombocythemia (ET). Recent evidence has shown differences in the clinical profile of patients with JAK2 mutation compared to CALR gene mutation and the inter-group difference between type 1 and type 2 variants of CALR gene mutation. Additionally, research suggests that there may be variations in thrombosis risk among different CALR mutations.

Aims: Quantify the association of CALR gene type 1 vs. type 2 mutation and its risk of thrombosis in patients with ET.

Methods: Relevant studies on the relationship between CALR gene mutations and thrombosis in patients with essential thrombocythemia were identified through searches of PubMed, Google Scholar, Medline OVID, Cochrane library, and CINAHL. The overall odds ratio was calculated using a random-effects model, statistical heterogeneity estimated using Cochran's Q statistics, I² tests, and subgroup analyses were conducted based on the type of thrombosis, timing, geographical location, and WHO diagnostic criteria.

Results: The meta-analysis included 1353 patients from 16 studies published between 2014 and 2022. The pooled OR of thrombosis with the CALR gene was 1.55 (95% confidence interval [CI]: 1.04-2.30, I2=0%) in the CALR type 1 variant compared to those with CALR type 2 variant. There was no statical difference in the sub-group analysis based on the type of thrombosis (arterial vs. venous thrombosis) between the two variants. Furthermore, no statical difference was observed in the thrombosis rates in patients of different geographical locations(Europe/US vs. Asia), WHO 2008 vs. 2016 classification, and timing of thrombosis.

Conclusion(s): The CALR gene type 1 variant is significantly associated with a 55% increase in thrombosis risk compared to the type 2 variant in patients with ET. Further research is needed to understand this association and the potential use of CALR gene mutation status for thromboprophylaxis.