Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia by Liu C, Kawedia J D, Cheng C, Pei D, Fernandez C A, Cai X, Crews K R, Kaste S C, Panetta J C, Bowman W P, Jeha S, Sandlund J T, Evans W E, Pui C-H, Relling M V in Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2012). PubMed

Abstract

Hypersensitivity to asparaginase is common but the differential diagnosis can be challenging, and the diagnostic utility of antibody tests is unclear. We studied allergic reactions and serum antibodies to E. coli-asparaginase (Elspar) in 410 children treated on St. Jude Total XV protocol for acute lymphoblastic leukemia. Of 169 patients (41.2%) with clinical allergy, 147 (87.0%) were positive for anti-Elspar antibody. Of 241 patients without allergy, 89 (36.9%) had detectable antibody. Allergies (P=0.0002) and antibodies (P=6.6 × 10(-6)) were higher among patients treated on the low-risk than among those on the standard/high-risk arm. Among those positive for antibody, the antibody titers were higher in those who developed allergy than in those who did not (P<1 × 10(-15)). Antibody measures at week 7 of continuation therapy had a sensitivity of 87-88% and a specificity of 68-69% for predicting or confirming clinical reactions. Antibodies inversely associated with serum asparaginase activity (P=7.0 × 10(-6)). High antibodies associated with a lower risk of osteonecrosis (odds ratio=0.83; 95% confidence interval, 0.78-0.89; P=0.007). Antibodies were related to clinical allergy and to low systemic exposure to asparaginase, leading to lower risk of some adverse effects of therapy.Leukemia accepted article preview online, 9 April 2012; doi:10.1038/leu.2012.102.

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