Abstract
Introduction and objectives: Myeloproliferative neoplasms (MPN) are a group of heterogeneous clonal hematopoietic disorders that comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). There is an increased risk of hemorrhage, thrombosis, cardiovascular (CV) event and transformation to myelofibrosis or acute leukemia. This study aims to review the clinicopathological characteristics and outcome, and prognostic indicators in a large Chinese population of patients with MPN.
Methods: Patients with the diagnosis of PV, ET, PMF and MPN-unclassifiable were recruited from 2012 to 2016 in a tertiary referral center in Hong Kong. Retrospective data from the date of diagnosis were retrieved from the clinical records and reviewed by independent investigators. Progression-free survival (PFS) was defined as the duration from diagnosis to transformation to myelofibrosis, acute leukemia or death. Overall survival (OS) was defined from the duration from diagnosis to death or last follow-up. Categorical variables were compared using Pearson's chi-square or Fisher's exact test. PFS and OS were evaluated by Kaplan-Meier analysis and were compared by log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model.
Results: 285 patients (142 men, 143 women) were included. PV, ET, PMF and MPN-U accounted for 22%, 60.0%, 10% and 8% of cases respectively (Table 1). Cytogenetic information at diagnosis was available in 47.7% (n=136) of the patients, of which 83% (N=113) had normal karyotypes. No other recurrent chromosomal abnormalities were observed apart from loss of chromosome Y. Among 230 molecularly annotated patients, 70% (N=162) harbored JAK2 V617F mutation. In 28 JAK2 V617F negative patients, 50% (N=14) and 4% (N=1) had CALR and JAK2 exon 12 mutations respectively. 13 patients were triple negative for JAK2, CALR and MPL mutations. Of all patients, treatment included aspirin prophylaxis (92%, N=263), hydroxyurea (92%, N=261), pegylated interferon (10.5%, N=30) and ruxolitinib (6.3%, N=18). CV events were observed in 45 (16%) patients, including 21 transient ischemic attacks, 14 ischemic strokes, 7 acute myocardial infarctions and 2 acute limb ischemia. 34 (76%) events occurred at diagnosis and 11 (24%) occurred while patients were on treatment. Significant risks associated with CV events were age > 50 years (p=0.002) and hypertension (p=0.038). Diabetes mellitus (p=0.163), hyperlipidemia (p=0.699), smoking (p=0.085) and concurrent ischemic heart disease (p=0.470) were not shown to be significant. Progression to MF was observed in 17% (n=11) of PV patients (median follow-up: 14.7, 9.5-27.6 years) and 12% (n=21) of ET patients (median follow-up:10.7, 1.5 - 22.6 years). Leukemic transformation occurred in 9 patients (3%) (ET, N=3, primary MF, N=1, secondary MF, N=5) at a median follow-up of 10.4 (1.0 - 22.6) years. Age >60 years and presence of splenomegaly at diagnosis were associated with inferior PFS; and age >60 years was associated with infereior OS in PV/ET patients (Figure 1). Based on these clinical criteria, PV/ET patients were divided into 3 groups, viz., age > 60 years with splenomegaly (n=8), age < 60 years without splenomegaly (n=83), and others (n=97). The corresponding median PFS were 12.9, 25.5 and 17.4 years; whereas the corresponding median OS were 15.5, 15.2 and 27.2 years. Age>60 years and splenomegaly remained significant risks for inferior PFS in univariate analysis, whereas on multivariate analysis, splenomegaly was only the significant risk for inferior PFS(Figure 2).
Conclusion: This study showed that age >50 years and hypertension were associated with increased risk of cardiovascular events in MPN patients. Age > 60 years and splenomegaly on presentation were significant risks for disease transformation in PV/ET.
No relevant conflicts of interest to declare.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal