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Hypersensitivity or Development of Antibodies to Asparaginase Does Not Impact Treatment Outcome of Childhood Acute Lymphoblastic Leukemia

From the Departments of Pharmaceutical Sciences, Hematology-Oncology, and Biostatistics and Epidemiology, St. Jude Children’s Research Hospital, and Colleges of Pharmacy and Medicine, University of Tennessee, Memphis, TN.

Address reprint requests to Mary V. Relling, PharmD, Pharmaceutical Department, St. Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105; email mary.relling{at}stjude.org

PURPOSE: Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS).

PATIENTS AND METHODS: One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m² intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment. Erwinia asparaginase was used in case of clinical hypersensitivity to E coli but not for subclinical development of antibodies. Plasma antiasparaginase antibody concentrations were measured on day 29 of induction in 152 patients.

RESULTS: Antibodies were detectable in 54 patients (35.5%), of whom 30 (55.6%) exhibited hypersensitivity to asparaginase. Of the 98 patients who had no detectable antibodies, 18 (18.4%) had allergic reactions. Patients with antibodies were more likely to have a reaction than those without antibodies (P < .001). Among the 50 patients who experienced allergic reactions (including two for whom antibodies were not measured), 36 (72.0%) were subsequently given Erwinia asparaginase; seven (19.4%) reacted to this preparation. EFS did not differ among patients who did and did not have antibodies (P = .54), with 4-year EFS (± 1 SE) of 83% ± 6% and 76% ± 5%, respectively. Similarly, EFS did not differ among patients who did and did not develop allergic reactions (P = .68), with 4-year estimates of 82% ± 6% and 78% ± 5%, respectively.

CONCLUSION: In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.

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