Antithrombin and fibrinogen levels as predictors for plasma L‐asparaginase activity in children with acute lymphoblastic leukemia

Abstract

Background L‐asparaginase is a cornerstone treatment for children with acute lymphoblastic leukemia (ALL). However, immune reaction to the drug may increase the clearance or impair the function of L‐asparaginase and reduces its therapeutic efficacy. The objective of this study was to identify potential plasma proteins that could be used as proxies for L‐asparaginase activity. Methods Fibrinogen, von Willebrand factor antigen (VWF:Ag), total protein, and albumin levels as well as antithrombin (AT) and L‐asparaginase activities were measured in 97 children with ALL treated for prolonged period of time with L‐asparaginase. Binary logistic regression and a receiver operating characteristic (ROC) curve analysis were performed to evaluate the predictive value of plasma proteins for L‐asparaginase activity. Results Median E. coli L‐asparaginase activity was 220 IU/L (range, 0–1308) throughout the treatment period. L‐asparaginase activity was below 100 IU/L in 23% of measured samples. L‐asparaginase activity was inversely associated with AT activity, fibrinogen, total protein, and albumin levels (r = −0.63, −0.62, −0.57, and −0.45, respectively; P < 0.0001), but not with VWF:Ag. ROC curve analyses showed an intermediate accuracy of AT activity (area under the ROC curve [AUC] = 0.77) to detect specimens with subtherapeutic level of L‐asparaginase. An optimal accuracy was found when AT and fibrinogen were combined (AUC = 0.82; sensitivity = 75%; specificity = 82%; positive predictive value = 55%; negative predictive value = 92%) with cutoff values of 0.73 IU/mL and 1.85 g/L, respectively. Conclusions AT combined with fibrinogen levels could be used as a proxy to identify patients with therapeutic level of L‐asparaginase activity in the absence of real‐time asparaginase measurement during prolonged exposure to L‐asparaginase.

Lower incidence of clinical allergy with PEG‐asparaginase upfront versus the sequential use of native E. coli asparaginase followed by PEG‐ASP in pediatric patients with acute lymphoblastic leukemia

“…The incidence of clinical allergy in recent pediatric protocols with prolonged intensified PEG‐ASP therapy is lower than that found in historical controls in which native E. coli ‐ASP was used 14,30–32 . Nevertheless, there are few direct comparisons within the same protocol of both formulations in children, and these did not show significant differences in the allergy incidence 16,17 .…”

“…17 The lack of differences might be related to the low incidence of allergy in this population, occurring in only 2 of 118 patients, which may be related to the less intensive asparaginase treatment received in the patients analyzed. 31,32 In the Dana-Farber Cancer Institute protocol 05-001 a randomized comparison was made between IM native E.…”

“…The Children Cancer Group reported the results of a randomized comparison of PEG‐ASP IM versus native E. coli ‐ASP IM given to children with standard‐risk ALL, and the incidence of allergy did not differ 17 . The lack of differences might be related to the low incidence of allergy in this population, occurring in only 2 of 118 patients, which may be related to the less intensive asparaginase treatment received in the patients analyzed 31,32 . In the Dana‐Farber Cancer Institute protocol 05‐001 a randomized comparison was made between IM native E. coli ‐ASP versus intravenous PEG‐ASP given post‐induction.…”

Hepatoprotective effect of nanoniosome loaded Myristica fragrans phenolic compounds in mice‐induced hepatotoxicity

“…42 Due to albumin's oncotic properties, treating liver cirrhosis with albumin has been widely used to expand plasma volume and increase practical circulation volume, thereby alleviating cardiocirculatory changes caused by portal hypertension. 43 TP and Alb serum levels were increased after NLMP therapy, but it was not meaningful. Hartanto et al's results were the same as ours as the TP and Alb serum levels were not significantly changed after treatment of Korean native chicken with dietary nutmeg oil.…”

“…In contrast, Merlen et al illustrated that TP and Alb levels in plasma decreased after patients' treatment with LA 42 . Due to albumin's oncotic properties, treating liver cirrhosis with albumin has been widely used to expand plasma volume and increase practical circulation volume, thereby alleviating cardiocirculatory changes caused by portal hypertension 43 . TP and Alb serum levels were increased after NLMP therapy, but it was not meaningful.…”