Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy

Abstract

Background Leukocytosis has been associated with thrombosis and mortality in cancer patients. We explored the association of leukocytosis with venous thromboembolism (VTE) and early mortality in cancer patients initiating chemotherapy. Methods Data from a prospective, multicenter observational study of treatment-related complications in 4,405 ambulatory cancer patients initiating chemotherapy was used for this analysis. The association of leukocytosis, VTE and mortality during the course of chemotherapy was evaluated in univariate and multivariate analysis. Results Ninety-three patients (2.1%) developed VTE and 134 (3%) died over a median follow up of 75 days (range 0–384). Of 4391 patients with available baseline white blood cell (WBC) count, 561 (12.8%) had elevated pretreatment leukocyte counts, defined as WBC > 11×109 cells/L. VTE occurred in 25 of 561 patients (4.5%) with baseline leukocytosis compared to 68 of 3830 (1.8%) with WBC ≤ 11×109 cells/L (P<0.0001). Baseline leukocytosis was associated with VTE by multivariate analysis as well (HR 2.1, 95% confidence interval 1.3–3.4, p=0.003). Forty one patients (7.3%) with leukocytosis died compared to 92 (2.4%) with WBC ≤ 11×109 cells/L (P<0.0001). Baseline leukocytosis was associated with early mortality by multivariate analysis as well (HR 2.2, 95% confidence interval 1.5–3.3, p<0.0001). Mortality was greatest in patients with both leukocytosis and VTE. In multivariate analysis several factors were predictive of leukocytosis. Conclusions Elevated WBC, particularly neutrophils, is strongly associated with increased risk of VTE and mortality in cancer patients receiving systemic chemotherapy. Further studies are needed to elicit the mechanisms involved.

Thrombosis: tangled up in NETs

“…69 Cell-free DNA increases transiently during the course of chemotherapy in patients and in a mouse model. 70 Adding cell-free DNA isolated from in vitro chemotherapy-treated blood to recalcified plasma increases thrombin generation due to contact pathway activation.…”

Biomarkers for prediction of venous thromboembolism in cancer

“…Moreover, in this study, elevated absolute neutrophil and absolute monocyte counts but not lymphocytosis were associated with increased risk of VTE. 7 In the Registro Informatizado de la Enfermedad Trombo-Embólica (RIETE) registry that included 3805 cancer patients with acute VTE, those with leukocytosis had a 1.6-fold increased risk of recurrent VTE. 8 The exact causative role of leukocytosis in cancer-related VTE remains to be elucidated.…”

Development of a Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism in Patients With Cancer-Associated Venous Thromboembolism

“…These markers are being studied in the setting of a first VTE in the context of malignancy. 22,[31][32][33] They are likely to be soft outcomes for evaluation of recurrence, because they most likely will reflect the impact of the anticancer treatment (chemotherapy/radiation therapy) and could act as confounders in the VTE recurrence setting. Treatment strategy was not a predictor of recurrence.…”