MPN-103 A Real-World Evaluation of the Association Between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera: Analysis of Data From the REVEAL Study.

Abstract

Polycythemia Vera (PV) leads to elevated peripheral blood counts (PBCs) and increased thromboembolic events (TE) risk. The conventional model used to determine TE-risk and treatment strategy includes advanced age and TE-history. Association between TE-risk and elevated hematocrit (HCT) is established; association with white-blood-cell count (WBC) or platelet count (PLT) have not been assessed consistently. Evaluate association between elevated PBCs and TE-risk. Real-world Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159). Clinical practice. Included: ≥3 post-enrollment PBCs; excluded: post-enrollment TE without PBCs <6 months before that TE. Noninterventional. Association was assessed by the time-dependent covariate Cox-proportional hazards model. Time-to-first post-enrollment TE was modeled; for patients with no TE, time was censored at last visit. Each lab parameter was individually modeled with sex, age, disease duration, and TE-history at enrollment (baseline covariates) and treatment (time-dependent covariates). Thresholds included: HCT>45%, WBC>11×109/L, PLT>400×109/L. Alternative thresholds included: WBC<7, ≥7-<8.5; ≥8.5-<11, ≥11×109/L, WBC>12×109/L with controlled HCT≤45%, and PLT>600×109/L. Of 2510 enrolled, 2271 patients were included: median age, 67 years (range, 22-95); male, 54.1%; median disease duration, 4.1 years (range, 0-56.3), TE-history, 20.1%; receiving hydroxyurea, 52.6%; TEs, 4.7% (arterial, 1.3%; venous, 3.3%). HCT>45% vs ≤45% (HR=1.84 [95% CI, 1.234-2.749], P=0.0028), WBC>11 vs ≤11×109/L (HR=2.35 [1.598-3.465], P<0.0001), and PLT>400 vs ≤400×109/L (HR=1.60 [1.088-2.359], P=0.0170) were each associated with significantly increased TE-risk. WBC≥ 11 vs <7×109/L was associated with the highest TE-risk (HR=2.61 [1.594-4.262], P=0.0001). TE-risk was increased for PLT>600 vs ≤600×109/L, but not significantly (HR=1.37 [0.763-2.468], P=0.2913). WBC>12 vs ≤ 12×109/L was significantly associated with increased TE-risk at HCT≤45% (HR=1.95 [1.066-3.554], P=0.0300). In all models, advanced age, female sex, and TE-history were associated with increased TE-risk. The results demonstrate significant associations individually between elevated HCT, PLT, WBC (>11 and >12×109/L), and increased TE-risk. Elevated WBC (>12×109/L) is significantly associated with increased TE-risk when HCT is controlled, indicating that TE-risk may be reduced by controlling WBC as well as HCT. These data support incorporation of PBCs into risk stratification and treatment strategies for PV patients.