The Study of Thrombosis in JAK2^V617F Mutated Myeloproliferative Neoplasms

Introduction: Thrombosis is the most important risk factor affecting event-free survival and overall survival (OS) of patients with myeloproliferative neoplasms (MPNs). To explore the risk factors of thrombosis in patients with JAK2^V617F-mutated MPN, a cohort of 1537 Chinese patients with JAK2^V617F-mutated MPN was retrospectively analyzed for clinical characteristics, laboratory characteristics, cytogenetics, thromboembolism, disease progression and OS.

Methods: The qualitative data were compared by the Chi-square test or Fisher's test, and continuous variables were compared with the Mann-Whitney U test or Kruskal-Wallis test. The Kaplan-Meier method and multivariate Cox analysis were used to study the risk factors of thrombosis in patients with JAK2^V617F-mutated MPN.

Results: Among the 1537 MPN patients, 931, 468 and 138 had polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), respectively. The median follow-up time was 7 years (range 1-47), and 12.8% of patients (197/1537) died during this period. A total of 16.8% (259/1399) of PV and ET patients had secondary myelofibrosis, and 2.5% (38/1537) of patients developed acute myeloid leukemia (AML). Thrombosis events occurred in 43.9% (675/1537) of patients, among which 91.4%(617/675) were arterial thrombosis and 16.6% (112/675) were venous thrombosis. The number of thrombosis events in PV, ET and PMF patients was 439 (47.2%), 197 (42.1%) and 39 (28.2%), respectively. The multivariate analysis indicated that age≥60 years old (P=0.003, HR=1.76, 95% CI[1.214, 2.552]), HCT≥48% (P=0.022, HR=1.635, 95% CI[1.073, 2.492]), at least one cardiovascular risk factor (P=0.024, HR=1.559, 95% CI[1.061,2.291]), a history of thrombosis (P<0.0001, HR=2.313, 95% CI[1.573,3.401]), and JAK2^V617Fallele burden (V617F%) ≥50% (P=0.003, HR=1.804, 95% CI [1.221, 2.665]) are risk factors for thrombosis in JAK2^V617F-mutated MPN. According to the results of the multivariate analysis, a risk model of thrombosis was established and comprised low-risk (0 points), intermediate-risk (1 points) and high-risk (≥2 points) groups, among which the incidence of thrombosis was 9.1%, 33.7% and 72.9%, respectively.

Conclusions: The Chinese thrombosis risk model of JAK2^V617F-mutated MPN established in this study suggests that elderly patients with a history of thrombosis should reduce V617F%, control HCT to less than 48% and mitigate cardiovascular risk factors, all of which are necessary measures to prevent thrombosis in patients with JAK2^V617F-mutated MPN.