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.