Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia

C. Liu, J. D. Kawedia, C. Cheng, D. Pei, C. A. Fernandez, X. Cai, K. R. Crews, S. C. Kaste, J. C. Panetta, W. P. Bowman, S. Jeha, J. T. Sandlund, W. E. Evans, C. H. Pui, M. V. Relling

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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 (P0.0002) and antibodies (P6.6 × 10 6) were higher among patients treated on the low-risk arm than among those treated on the standardhigh-risk arm. Among those positive for antibody, the antibody titers were higher in those who developed allergy than in those who did not (P1 × 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 (P7.0 × 10 6). High antibody levels were associated with a lower risk of osteonecrosis (odds ratio0.83; 95% confidence interval, 0.78-0.89; P0.007). Antibodies were related to clinical allergy and to low systemic exposure to asparaginase, leading to lower risk of some adverse effects of therapy.

Original languageEnglish
Pages (from-to)2303-2309
Number of pages7
JournalLeukemia
Volume26
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • Allergy
  • Antibody
  • Asparaginase
  • Osteonecrosis
  • Pharmacodynamics

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