Antithrombin and fibrinogen levels may be viable proxies for estimating L-asparaginase activity in the absence of real-time measurements during extended exposure to L-asparaginase treatment for acute lymphoblastic leukemia (ALL) in pediatric patients, according to results published in Pediatric Blood and Cancer.

Treatment with L-asparaginase is foundational to pediatric ALL, but adverse immune responses to this treatment agent may increase clearance of the drug or impede L-asparaginase function and decrease its efficacy.

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In this study, researchers assessed plasma proteins that could serve as proxy biomarkers for L-asparaginase activity, such as fibrinogen, von Willebrand factor antigen (VWF:Ag), total protein, albumin, and antithrombin. Protein activity was monitored in 97 children with ALL who received extended treatment with L-asparaginase.

During the treatment period, median Escherichia coli L-asparaginase activity was 220 IU/L (range, 0-1308). Approximately one-fourth (23%) of collected blood samples demonstrated L-asparaginase activity under 100 IU/L.

Antithrombin activity (r = -0.63), fibrinogen (r = -0.62), total protein (r = -0.57), and albumin levels (r = -0.45) all inversely correlated with L-asparaginase activity (P <.0001). VWF:Ag, conversely, was not associated with L-asparaginase activity.

Antithrombin activity had intermediate accuracy in detecting samples with L-asparaginase activity levels below therapeutic benefit. When researchers combined antithrombin activity and fibrinogen, accuracy in detection of subtherapeutic L-asparaginase levels improved, with sensitivity of 75%, specificity of 82%, positive predictive value of 55%, and negative predictive value of 92%.

”The use of L-asparaginase is associated with a decrease in the production of hemostatic proteins,” wrote the authors. “However, when subtherapeutic L-asparaginase activity is suspected, additional tests…will be required to confirm the relevance of switching to another L-asparaginase preparation.”

Reference

1.     Merlen C, Bonnefoy A, Afeich C, et al. Antithrombin and fibrinogen levels as predictors for plasma L-asparaginase activity in children with acute lymphoblastic leukemia [published online April 2, 2019]. Pediatr Blood Cancer. doi:10.1002/pbc.27729