Aspagarinase is a fundamental component for the treatment of patients with acute lymphoblastic leukemia (ALL). Venous thromboembolism (VTE) is a known complication of asparaginase therapy during treatment for ALL. This is attributed to the depletion of anticoagulants, particularly acquired antithrombin deficiency following asparaginase administration. The incidence of thrombosis following asparaginase is more prevalent in adults versus children and is estimated to be around 5-35 % and 2.4-8% respectively. Multiple studies have investigated the efficacy and safety of antithrombin supplementation. The recent THROMBOTECT study showed that prophylactic use of antithrombin (AT) or low molecular weight heparin (LMWH) is associated with significant risk reduction of thromboembolism in children and adolescents during induction chemotherapy of ALL. Our study sought to review the cohort studies comparing VTE in adults with and without AT supplementation in ALL receiving asparaginase and specifically evaluate the efficacy of this strategy.
We performed a systematic search using PubMed, Google Scholar, EMBASE, SCOPUS and ClinicalTrials.gov without language restriction up until July 20th 2020. A random effects model was utilized to calculate risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI).
Eight studies fulfilled our inclusion criteria (table 1) and were retrospective cohort studies. In adult patients, with ALL treated with asparaginase, the incidence of VTE was significantly lower in those who received AT [RR=0.46 (95 % CI= 0.31-0.70; p= 0.0002) (figure 1.1). The threshold for AT supplementation was 60-70% in most of the studies, with the exception of two studies where the threshold was 50%.
In our meta-analysis of the current available data,Antithrombin supplementation in adults with ALL receiving asparaginase was associated with a significant decrease in the risk of venous thromboembolism compared to those who didn't receive thromboprophylaxis. Our data suggest the benefit of antithrombin supplementation in adults with ALL treated with asparaginase. We suggest that this strategy be implemented in a large prospective clinical trial to further confirm the benefit of this intervention.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.