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Elevated White Blood Cell Levels and Thrombotic Events in Patients with Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data


 Introduction:
 Patients with polycythemia vera (PV) have poor overall survival compared with the general population, with arterial and venous thrombotic events (TEs) representing a substantial source of morbidity and mortality. A subanalysis of the Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) study demonstrated a significant correlation between white blood cell (WBC) count ≥11 × 109/L and time-dependent risk of major thrombosis (hazard ratio, 3.9; 95% CI, 1.24-12.3). The objective of this analysis was to describe the association between WBC levels and occurrence of TEs among patients with PV from a large, real-world population.
 Methods:
 This was a retrospective, observational study using Veterans Health Administration claims data collected between 10/1/05, and 9/30/12. Patients with ≥2 claims for PV (ICD-9-CM code 238.4) ≥30 days apart during the identification period (10/1/06 to 9/30/07) were eligible for analysis. The earliest date for a PV claim within the identification period was designated as the index date. All patients were ≥18 years of age, had no TEs before the index date, and had continuous health plan enrollment with medical and pharmacy benefits ≥12 months pre-index. Patients were followed up until death, disenrollment, or end of study period, whichever occurred first. Patients with ≥3 WBC values per year on average during the follow-up period and, for patients with a TE, ≥1 WBC value before the TE were included in the analysis. Based on the last measurement before the TE or end of follow-up, patients were assigned to one of the following WBC categories: WBC <7.0, 7.0-8.4, 8.5-<11.0, and ≥11.0 × 109/L. A univariate Cox proportional hazards model was used to compare the risk of TEs between WBC categories using <7.0 × 109/L as the reference group.
 Results:
 A total of 1565 US veterans with PV were included in the analysis (WBC [× 109/L] <7.0, n=428 [27.3%]; 7.0-8.4, n=375 [24.0%]; 8.5-<11.0, n=284 [18.1%]; ≥11.0, n=478 [30.5%]). Patient demographics were similar across groups (Table 1). The mean Charlson Comorbidity Index and Chronic Disease Scores were similar across groups and ranged from 1.11-1.45 and 6.15-6.76, respectively. Hypertension was the most common comorbid condition among patients across all WBC categories (65.1%-71.5%). Mean follow-up times across groups ranged from 3.6 to 4.5 years. Rates of cytoreductive treatment, including phlebotomy, were similar across WBC groups and ranged from 77.3% to 78.2% (any cytoreductive treatment) and 56.9% to 65.9% (phlebotomy). The mean number of phlebotomies per patient per year was 2.6, 2.6, 4.7, and 3.0 among patients with WBC counts <7.0, 7.0-8.4, 8.5-<11.0, and ≥11.0 × 109/L, respectively. Overall, 390 patients (24.9%) experienced a TE during the study period, including 85 patients (19.9%) with WBC <7.0 × 109/L, 91 patients (24.3%) with WBC 7.0-8.4 × 109/L, 73 patients (25.7%) with WBC 8.5-<11.0 × 109/L, and 141 patients (29.5%) with WBC ≥11.0 × 109/L (Figure 1). Compared with the WBC <7.0 × 109/L reference group, the hazard ratios (95% CI) for TEs were 1.22 (0.91-1.64; P=0.1835), 1.39 (1.02-1.90; P=0.0401), and 1.81 (1.39-2.38; P<0.0001) among patients with WBC counts 7.0-8.4, 8.5-<11.0, and ≥11.0 × 109/L, respectively (Table 1).
 Conclusion:
 A significant, positive association between increased WBC counts and occurrence of TEs in patients with PV was observed in this study. Patients with WBC counts ≥8.5 × 109/L had a significantly increased risk of TE, and those with counts ≥11.0 × 109/L were at greatest risk. Effective control of WBC counts is an important component of disease management and may reduce risk of TEs in patients with PV.
 
 
 
 Parasuraman: Incyte: Employment, Equity Ownership. Yu:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Shrestha:STATinMED Research: Employment, Equity Ownership. Wang:STATinMED Research: Employment, Equity Ownership. Baser:STATinMED Research: Employment, Equity Ownership. Scherber:Gilead: Honoraria.
