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Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia

Leukemia volume 26, pages 2303–2309 (2012)Cite this article

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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.

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Acknowledgements

This work was supported by NCI grants CA 142665, CA 36401 and CA 21765 and the NIH/NIGMS Pharmacogenomics Research Network (U01 GM92666), and by the American Lebanese Syrian Associated Charities (ALSAC). We thank the clinical staff, research nurses, patients and their parents for participation; Dr Wenjian Yang, Nancy Kornegay and Mark Wilkinson for computational assistance and data preparation; May Chung and Natalya Lenchik for asparaginase antibody assays; Dr Laura Ramsey and Dr Colton Smith for insightful comments; and Dr David Armbruster for manuscript editing.

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Authors and Affiliations

  1. Departments of Pharmaceutical Sciences, TN, Memphis, USA

    C Liu, J D Kawedia, C A Fernandez, X Cai, K R Crews, J C Panetta, W E Evans & M V Relling

  2. University of Tennessee Health Science Center, TN, Memphis, USA

    C Liu & S C Kaste

  3. Departments of Biostatistics, TN, Memphis, USA

    C Cheng & D Pei

  4. Departments of Radiological Sciences, Memphis, TN, USA

    S C Kaste

  5. Cook Children’s Hospital, Fort Worth, TX, USA

    W P Bowman

  6. Departments of Oncology, St Jude Children’s Research Hospital, TN, Memphis, USA

    S Jeha, J T Sandlund & C-H Pui

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  1. C Liu
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Correspondence to M V Relling.

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Competing interests

MVR receives a portion of the income St Jude receives from licensing patent rights related to TPMT and GGH polymorphisms, and receives funding for investigator-initiated research on the pharmacology of asparaginase from Sigma-Tau Pharmaceuticals. WEE receives a portion of the income St Jude receives from licensing patent rights related to TPMT and GGH polymorphisms. All other authors declare no conflict of interest.

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Liu, C., Kawedia, J., Cheng, C. et al. Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia. Leukemia 26, 2303–2309 (2012). https://doi.org/10.1038/leu.2012.102

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