Clinical Features and Mutational Landscape of Patients Referred for Suspected Essential Thrombocytosis: A Descriptive Study Using a 'Real-World’ Database

Abstract

Background: Essential Thrombocythemia (ET) is a myeloproliferative neoplasm characterized by persistent thrombocytosis and often associated with mutations in JAK2, CALR, or MPL. Next Generation Sequencing (NGS) has become widely used in patients with suspected hematologic malignancies but its role in the investigation of unselected patients referred for thrombocytosis remains to be defined. This project describes the characteristics and mutational landscape of patients referred for isolated thrombocytosis with the aim of developing a clinical prediction rule for ET to help guide diagnosis and improve utilization of genomic testing. Methods: All adult patients referred to the Hematology Service at London Health Sciences Centre, Ontario, Canada, between January 1, 2018, and May 31, 2021 were reviewed for thrombocytosis (≥ 450 x 109 cells /L). NGS testing was performed using the Oncomine Myeloid Research Assay (Thermofisher Scientific, MA, USA). Patients were classified into two groups: Clinical ET and secondary thrombocytosis. Clinical ET was defined as any patient meeting the World Health Organization (WHO) 2016 criteria for ET or any patient meeting all criteria but lacking a bone marrow biopsy. Results: 446 consecutive patients were evaluated for thrombocytosis with NGS testing. 102 patients were excluded due to meeting criteria for other WHO defined conditions such as chronic myeloid leukemia, polycythemia vera, other myeloproliferative neoplasms and/or myelodysplastic syndromes. In the remaining, 342 patients, the overall yield of molecular testing was 188 (55.0%). Mutations in JAK2, CALR, MPL were identified in 84.7% of patients with clinical ET (JAK2 in 48.9%, CAL-R type 1 or 2 in 27.6%, and MPL in 8.5%), with triple negative making up the remaining 8.5%. There was no statistically significant difference between CBC parameters, ferritin, ESR, and CRP between clinical ET and secondary thrombocytosis groups. In contrast, clinical factors such as previous history of arterial thrombosis were highly predictive of ET, whilst active malignancy, chronic inflammatory disease and post splenectomy and iron deficiency were all associated with secondary thrombocytosis. Conclusion: Overall yield of molecular testing for this population of patients referred for thrombocytosis was high (55.0%), suggesting appropriate use of NGS testing, but the identification of clinical factors predicting secondary causes might suggest further improvement in utilization. In our cohort, CBC parameters did not readily distinguish between ET and secondary thrombocytosis. Clinical factors such as smoking, active malignancy, chronic inflammatory disease and post splenectomy and iron deficiency are associated with secondary thrombocytosis. These results may help inform development of a clinical prediction rule to assist in determining the pre-test probability of ET in patients referred for thrombocytosis. #co-first authors Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal