Thrombosis among 1537 patients with JAK2V617F -mutated myeloproliferative neoplasms: Risk factors and development of a predictive model.

Yuhui Zhang,Yan Wang,Yuan Zhou,Huiqin Zhang,Yingshao Wang,Dapeng Li,Chenxiao Du,Jie Bai,Guangshuai Teng,Lixia Fu,Yanqi Li,Kangyin Chen,Yafang Chen

doi:10.1002/cam4.2886

Abstract

To explore the risk factors of thrombosis in patients with JAK2V617F‐mutated myeloproliferative neoplasms (MPNs), a cohort of 1537 Chinese patients with JAK2V617F‐mutated MPN was retrospectively analyzed. The Kaplan‐Meier method and multivariate Cox analysis were used to study the risk factors of thrombosis in patients with JAK2V617F‐mutated MPN. 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). Thrombotic 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 thrombotic 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, HCT ≥48%, at least one cardiovascular risk factor, a history of thrombosis, and JAK2V617F allele burden (V617F%) ≥50% are risk factors for thrombosis in JAK2V617F‐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%. For elderly patients with JAK2V617F‐mutated MPN and a history of thrombosis, reducing the V617F%, controlling HCT and preventing cardiovascular risk factors are necessary measures to prevent thrombosis.

Highlights

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are chronic myeloproliferative diseases caused by clonal expansion of malignant hematopoietic stem/progenitor cells
Thrombosis-related deaths accounted for 45%, 26%, and 12% of deaths in patients with polycythemia vera (PV), essential thrombocythemia (ET), and PMF17-19; thrombosis is considered the most important cause of death and disability of MPN patients, and the study of thrombosis is a consistent topic in the field of MPN
primary myelofibrosis (PMF) patients with JAK2V617F and MPLW515L/K mutations have a higher risk of thrombosis and worse prognosis than patients with CALR mutations, and CALR type I mutations corresponded to better prognosis than CALR type II mutations.[9,22]

Summary

| INTRODUCTION

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are chronic myeloproliferative diseases caused by clonal expansion of malignant hematopoietic stem/progenitor cells. MPNs mainly include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).[1] Thrombosis, leukemic transformation, and myelofibrotic transformation are critical complications of MPN and are highly common in patients with MPN.[2,3,4,5,6] Fatalities due to thrombosis account for 35%~70% of the total mortality rate of MPN, making it the most important risk factor affecting eventfree survival and overall survival (OS) of MPN patients.[7]. Studies in the last decade have shown that JAK2/CALR/MPL gene mutations are the driver mutations in MPN.[8,9,10] Among those, the JAK2V617F mutation is considered the most common driver mutation of MPN and is detected in 95% of PV patients and 60% of ET and PMF patients.[11]. We analyzed the clinical features, disease progression, and survival status of 1573 MPN patients with JAK2V617F mutation and explored the risk factors affecting thrombosis in patients with JAK2V617F-mutated MPN

| METHODS

| RESULTS

| DISCUSSION