Next Generation Sequencing Identifies Subgroups of Patients With Triple Negative Primary Thrombocytosis With Different Clinical Thrombotic Outcomes

Abstract

Introduction

The majority of patients with essential thrombocythemia (ET) show somatic mutations of JAK2, CALR, or MPL. Around 10% of cases lack these mutations (“triple negative” ET, TN-ET). Additionally, some patients with bona fide “primary thrombocytosis” (PT) [i.e., high platelet (PLT)- count with no apparent underlying causes] do not fulfill the histologic criteria of ET. In this context, Next Generation Sequencing (NGS) can provide evidence of clonality and identify patients with different clinical behaviors.

Methods

We conducted a retro-prospective analysis of 39 patients with TN-PT and correlated the clinical and pathologic features with the molecular findings.

Results

Bone marrow histopathological features were consistent with ET in 60% of cases. After a mean follow up of 11.1 years, no cases of secondary myelofibrosis nor acute leukemia were observed. We reported 15 thrombotic events (TEs) in 10 (25.6%) patients. Considering mutations with a variant frequency ≥ 5%, 15.4% of patients showed at least one mutation (“NGS-positive”); the remaining had no mutations (“NGS-negative”). NGS status predicted the incidence of TEs: NGS-positive patients experienced a significantly higher rate of TEs compared to NGS-negative patients (66.6% vs. 18.2%, respectively; p = 0.01).

Conclusion

NGS status represents an adjunctive risk factor for thrombosis in TN-PT and provides useful clinical information.