title: Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia.
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 arm than among those treated 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. The level of antibodies was inversely associated with serum asparaginase activity (P=7.0 × 10(-6)). High antibody levels were 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.
authors.affiliation: Department of Pharmaceutical Sciences, Memphis, TN, USA.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: J D
authors.initials: JD
authors.lastname: Kawedia
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: D
authors.initials: D
authors.lastname: Pei
authors.forename: C A
authors.initials: CA
authors.lastname: Fernandez
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: K R
authors.initials: KR
authors.lastname: Crews
authors.forename: S C
authors.initials: SC
authors.lastname: Kaste
authors.forename: J C
authors.initials: JC
authors.lastname: Panetta
authors.forename: W P
authors.initials: WP
authors.lastname: Bowman
authors.forename: S
authors.initials: S
authors.lastname: Jeha
authors.forename: J T
authors.initials: JT
authors.lastname: Sandlund
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: C-H
authors.initials: CH
authors.lastname: Pui
authors.forename: M V
authors.initials: MV
authors.lastname: Relling
mesh_terms: D000906:Antibodies / Q000097:blood*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D001215:Asparaginase