Allergic Reactions to E. coli Asparaginase are Associated with Decreased Asparaginase Activity in an Indonesian Pediatric Population with ALL

Sari, Nur Melani; Berbudi, Afiat; Susanah, Susi; Reniarti, Lelani; Supriyadi, Eddy; Kaspers, Gertjan J L; Buddington, Randal K; Howard, Scott; Idjradinata, Ponpon

doi:10.31557/APJCP.2023.24.8.2773

Allergic Reactions to E. coli Asparaginase are Associated with Decreased Asparaginase Activity in an Indonesian Pediatric Population with ALL

Document Type : Research Articles

Authors

¹ Hematology Oncology Division, Department of Child Health Faculty of Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, Indonesia.

² Department of Biomedical Science, Division of Parasitology, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia.

³ Pediatric Hematology Oncology Division, Department of Pediatrics, Dr Sardjito Hospital- Faculty of Medicine Universitas Gajah Mada,Yogyakarta, Indonesia.

⁴ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.

⁵ Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, pediatric oncology, The Netherlands.

⁶ University of Tennesse, Health Science Centre, Memphis, United States of America.

10.31557/APJCP.2023.24.8.2773

Abstract

Purpose:The asparaginase’s (ASP) utility for ALL treatment is limited by neutralizing antibodies, which is problematic in countries whose access limited to alternative preparations. ASP antibody levels and activity was measured during remission induction and associated with allergy manifestations. Methods: E. coli ASP was dosed at 7500 IU/m2. ASP IgG antibody levels were quantified at the beginning and end of induction. ASP activity was measured 24 hours after 1st and 5th dose (standard-risk) or 7th dose (high-risk patients) administration, and within 24 hours in case of allergic reactions. Allergy was monitored by CTCAE version 3. Parametric and non-parametric was performed for data analysis. Results:ASP antibody and activity levels were available in 41/63 consecutive patients. Allergic manifestations occurred in 13/41, with urticaria being the most frequent. There were no significant differences in subject characteristics based on allergic reactions. The 5th dose was the most frequent time of onset. Antibody levels in allergy group at the end of induction did not differ from those at baseline (p<0.05). Using a 24-hour level of 100 mU/mL as a threshold for adequate ASP activity, 6/13 patients with allergy had adequate levels compared to 26/28 patients without (p<0.05). The ASP activity level at the end of induction phase in both groups did not show a significant decrement. Conclusion: The E. coli ASP activity with adequate levels were significantly higher in non-allergy group. Its activity level was not accompanied by increment of IgG in allergic group indicates other factors might affect activity levels in allergy group.

Keywords