Clinical and Laboratory Associations of JAK2 V617F Variant Allele Frequency in Patients With JAK2 V617F-Positive Erythrocytosis: A Single-Centre Retrospective Analysis.

BACKGROUND

JAK2 V617F variant allele frequency (VAF) reflects clonal burden in myeloproliferative neoplasms, but the clinical associations of low-level VAF in patients with erythrocytosis remain uncertain.

OBJECTIVE

The objective of this study is to examine associations between diagnostic JAK2 V617F VAF categories and clinical, laboratory, bone marrow and thrombotic outcomes in patients with JAK2 V617F-positive erythrocytosis.

PATIENTS AND

METHODS

This single-centre retrospective cohort included 174 adults. Patients were stratified by diagnostic VAF as low (< 5%; n = 62), intermediate (5%-50%; n = 81) or high (> 50%; n = 31). Clinical and laboratory characteristics, bone marrow findings and incident thrombotic events during follow-up were compared. Multivariable logistic regression was used to evaluate factors associated with thrombosis.

RESULTS

Follow-up duration was comparable amongst the VAF groups (median, 5.0 vs. 8.0 vs. 6.0 years; p = 0.227). Thrombosis rates increased across the groups (12.9% vs. 22.2% vs. 48.4%; p = 0.001), as did splenomegaly (25.8% vs. 53.1% vs. 64.5%; p < 0.001) and myelofibrosis transformation (1.6% vs. 13.6% vs. 20.0%; p = 0.011). Amongst patients with available measurements, median serum erythropoietin decreased with higher VAF (8.0 vs. 3.1 vs. 2.2 mIU/mL; p < 0.001), whereas the proportion with subnormal erythropoietin increased (17.8% vs. 47.6% vs. 82.6%; p < 0.001). Amongst biopsied patients, polycythemia vera-supportive bone marrow morphology was present in 50.0%, 93.5% and 100% of the groups respectively. A diagnostic VAF > 50% was independently associated with subsequent thrombosis (OR: 3.35; 95% CI: 1.06-10.58; p = 0.039), as was platelet count (OR: 9.92; 95% CI: 1.52-64.63; p = 0.016).

CONCLUSIONS

A diagnostic JAK2 V617F VAF > 50% was independently associated with subsequent thrombosis in this cohort. The low-VAF group was diagnostically and clinically heterogeneous. These findings should be considered hypothesis-generating and require prospective validation.