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Keywords:

  • childhood acute lymphoblastic leukemia;
  • Erwinia asparaginase;
  • asparaginase antibodies;
  • asparaginase pharmacokinetics

Abstract

Background

Determination of the frequency of antibody formation during first and second exposure to Erwinia asparaginase after i.v. and i.m. administration.

Procedure

Thirty-nine children with newly diagnosed acute lymphoblastic leukemia (ALL) were included in this prospective study. Antibodies were determined (ELISA method) in plasma from these patients on specific days during and after therapy with 30,000 IU/m2 i.v. or i.m. every day for ten days during the induction phase (first exposure). For 19 children, antibodies were measured in plasma during and after the re-induction phase (second exposure) following treatment with 30,000 IU/m2 i.v. or i.m. twice a week for two weeks (Mondays and Thursdays). On the same days of therapy, enzyme activity (spectrophotometric method) and the concentration of asparagine (HPLC) was determined.

Results

During the first exposure, none of the patients developed anti-Erwinia asparaginase antibodies. During the second exposure, one patient (1 of 8 patients) treated intravenously developed antibodies, which were associated with disappearance of enzyme activity and reappearance of asparagine. Three of eleven patients developed antibodies of pharmacokinetic importance after i.m. therapy. None of the children had any clinical symptoms of hypersensitivity.

Conclusions

The formation of antibodies and subsequently altered pharmacokinetics of Erwinia asparaginase seemed to be of importance only during a second period of asparaginase therapy. Med. Pediatr. Oncol. 2002;38:310–316. © 2002 Wiley-Liss, Inc.