Abstract A089: Antithrombin III and fibrinogen activity as surrogate markers in predicting therapeutic asparaginase activity levels in children with acute lymphoblastic leukemia
Authors: Morales Sonia , Williams Edith , Kasper Kirsten , Zabokrtsky Keri , Sayrs Lois , Nugent Diane , Huynh Van 
Published: January 2023

Abstract
Background. The incorporation of asparaginase has played an important role in improving survival rates in pediatric patients treated for acute lymphoblastic leukemia (ALL). Measuring asparaginase levels is one method to determine the efficacy of this chemotherapy. Determination of antithrombin III (ATIII) and/or fibrinogen (FIB) activity can be clinically useful as indirect asparaginase (ASP) level assessments since serum assays of ASP levels are not widely available, can be costly, and are performed at specialized labs. Previous studies have identified ATIII and FIB as potential markers in characterizing low or undetectable asparaginase activity in pediatric patients with ALL. The objective of this study was to determine whether FIB and ATIII levels can be used as surrogate markers in predicting therapeutic ASP activity in a predominantly Hispanic ALL population. Methods. FIB and ATIII levels were collected prior and 7 days post PEG-asparaginase (PEG) infusion. ASP levels were collected 7 days post-PEG. Mean differences in levels of FIB and ATIII activity were compared using t-tests for means and Mann-Whitney tests for medians. The Spearman correlation was used to evaluate the association between asparaginase activity, FIB, and ATIII levels. Unadjusted odds ratios were calculated to assess the predictive value of differences from baseline to Day 7 in ATIII and FIB levels associated with therapeutic levels (≥ 0.1 IU/mL). Results. Twenty patients were enrolled. The cohort was predominantly Hispanic (60%) and male (68%) with a median age of 8 years [range 2-19]. The median FIB level post-PEG was 155 mg/dL [nl 212-466] and the median ATIII activity level was 61% [nl 84-125] in those with therapeutic ASP levels. A median decrease in FIB and ATIII activity levels of 52% were seen with therapeutic ASP levels. By contrast in those with non-therapeutic levels, the difference was 7% and 28%, respectively. The bivariate correlation between ATIII and 7-day asparaginase levels was significant when controlling for BMI (Spearman’s ρ=0.62, p=0.001); the 7-day association between ASP and FIB was not influenced by BMI (Spearman’s ρ=-0.46, p=0.05). FIB and ATIII were correlated (Spearman’s ρ =.47;p=0.03). Both FIB (OR=0.004[0.0003-0.44]; p=0.02) and ATIII (OR=0.004[0.0002-1.0]; p=0.04) demonstrated reduced odds of higher therapeutic levels compared to lower therapeutic levels when mediated by Hispanic ethnicity. ATIII mean changes baseline to Day 7 were significantly smaller for Hispanic ethnicity [(Hispanic =-0.45(0.18) vs. Non-Hispanic =0.52(0.05); p=0.05)]. There were no significant differences in FIB by Hispanic ethnicity. Conclusions. Decreases in ATIII levels from baseline are associated with reduced odds of therapeutic asparaginase levels while decreased FIB levels may also indicate subtherapeutic levels. Hispanic ethnicity appears to mediate the observed effects from ATIII. ATIII and FIB levels may be important indirect markers in ASP activity monitoring when serum asparaginase assays are unavailable.
Citation Format: Sonia Morales, Edith Williams, Kirsten Kasper, Keri Zabokrtsky, Lois Sayrs, Diane Nugent, Van Huynh. Antithrombin III and fibrinogen activity as surrogate markers in predicting therapeutic asparaginase activity levels in children with acute lymphoblastic leukemia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A089.