Silent hypersensitivity toEscherichia coliasparaginase in children with acute lymphoblastic leukemia

Abstract

This prospective study aimed to assess the incidence of silent hypersensitivity to Escherichia coli asparaginase in the treatment of acute lymphoblastic leukemia (ALL). Thirty-three children with newly diagnosed ALL were included in the study and treated according to the FRALLE 2000 protocol. The 'A group' (n = 18) differed from the 'B-T group' (n = 15) by a less intensive chemotherapy, the absence of concurrent prednisone therapy, and different asparaginase administration modalities during the second intensification. Asparagine, asparaginase activity, and anti-asparaginase antibodies were measured in each phase before the next injection of asparaginase. Eighteen percent of children presented a silent hypersensitivity. Most of them were in the 'B-T group' (p = 0.07), and maintained low antibody titers throughout the treatment. Clinical hypersensitivity was statistically more frequent in group A (p = 0.002), and allergy occurred mainly during the second intensification when antibody concentrations were significantly increased. We did not find any significant difference between asparaginase activity or asparagine depletion between the silent hypersensitivity and clinical allergy groups. In all, the results of this study suggest that chemotherapy and corticosteroid therapy associated with asparaginase treatment can lower antibody production and contribute to maintaining a silent hypersensitivity state.

Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation

“…18 This cut-off of ≥ 0.1 IU/mL has been confirmed and used in many clinical trials. 9,19,[22][23][24] The question arises whether a lower threshold, for example of 0.05 IU/mL, also leads to complete asparagine depletion. Rizzari and colleagues showed that trough asparaginase activity levels of < 0.05 IU/mL, obtained either with native E. Coli or Erwinia asparaginase, resulted in serum and CSF asparagine depletion in children with ALL.…”

Anti–Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials

“…8,12 These were characterized by insufficient ASE activity because of inactivating Abs. Because silent inactivation can be detected by measuring the ASE activity in the serum, investigators in the ALL-BFM trials implemented monitoring of ASE activity more than a decade ago.…”

Allergic reactions and antiasparaginase antibodies in children with high‐risk acute lymphoblastic leukemia: A children's oncology group report

“…(10, 12-16) Erwinia ASNase was associated with less allergic reactions when compared to both PEG ASNase and native ASNase during IM #1 only. In all other phases of therapy, there was no significant difference in incidence of allergic reactions.…”