Silent hypersensitivity to Escherichia coli asparaginase 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.

Keywords:

• Allergy and hypersensitivity
• the humoral immune response
• lymphoid leukemia

Acknowledgements

We thank Cyril Flamant and Christèle Volteau for helpful advice. We thank the nurses and physicians of the Pediatrics Onco-Hematology Unit of the University Hospital of Nantes for dedicated patient care.

Declaration of interest: This work was supported by the University Hospital of Nantes, Nantes, France. M.M. would also like to thank the ‘Région Pays de Loire,’ the ‘Association pour la Recherche sur le Cancer (ARC),’ the ‘Fondation de France,’ the ‘Fondation contre la Leucémie,’ the ‘Agence de Biomédecine,’ the ‘Association Cent pour Sang la Vie,’ and the ‘Association Laurette Fuguain’ for their generous and continuous support for our clinical and basic research work.

A.M. was an employee of EUSA Pharma at time of this study.