Arterial thrombotic events in lymphoma patients: Systematic review and meta-analysis

Abstract

Abstract Introduction: Arterial thrombotic events (ATE) represent a serious but underreported complication in lymphoma patients, potentially impacting morbidity and mortality. The prevalence of ATE among lymphoma patients shows considerable variation across studies, influenced by multiple factors and consequently dynamic during the course of the disease. The reason lies in marked heterogeneity of lymphoma, with unique characteristics depending on the specific subtype, status of the disease, patient characteristics and treatment modalities. The systematic review and meta-analysis aimed to provide the pooled prevalence of ATE in lymphoma patients and identify associated risk factors. Methods: A systematic review and meta-analysis were performed following PRISMA guideline. The search for studies included several electronic databases: PubMed, Web of Science, Cochrane Library, Scopus - all up to June 2024. The inclusion criteria were adult study population, with any type of newly diagnosed, relapsed or previous diagnosis of Hodgkin or non-Hodgkin's lymphoma. Extracted data implied: basic study characteristics, participant characteristics, intervention details and outcomes. The Newcastle-Ottawa scale was used to analyse the quality of included studies. For the pooling of single proportions, we used the inverse variance methods with logit transformation. Confidence intervals for individual studies were estimated using the Clopper-Pearson method. The heterogeneity between studies was explored using Cochran's Q test and r2 statistics, the Baujat plot, and quantified with the l2 statistic. Univariate meta-regression analyses were used to identify potential predictors. Publication bias was assessed using the funnel plot and Egger's test. Sensitivity analysis was performed by excluding studies that might influence the results of the meta-analysis. A significance level of 0.05 was applied. Results: Final analysis included six studies comprising 9293 patients. Across the studies, 63 ATE were reported. The pooled estimation of events was 1.23% (95% CI: 0.47% to 3.20%) under the random-effects model, with the prediction interval ranged from 0.04% to 28.61%, demonstrating significant heterogeneity (I² = 92.4%). According to Baujat plot, only one study had a disproportionate influence on heterogeneity. Sensitivity analysis excluding the influential study revealed a slight increase in the pooled rate (1.82%), with reduced heterogeneity (I² = 81.2%). Disproportion of the overall heterogeneity has arisen probably due to methodological or population differences. However, the value of the pooled effect remained consistent. A symmetrical funnel plot (Egger's test p = 0.809) showed no significant publication bias. Univariate meta-regression analysis revealed that increasing mean age was significantly associated with a higher prevalence of arterial thrombosis. Variables as follow-up duration and female gender proportion didn't show a significant association with event rates. Conclusions: ATE are less common than venous thrombotic events in lymphoma but remain clinically relevant. This meta-analysis identifies a low pooled event rate of ATE and increasing mean age as a significant associated variable, emphasizing the need for proper risk-adapted thromboprophylaxis strategies in lymphoma patients.