Allergic reactions to asparaginase: retrospective cohort study in pediatric patients with acute lymphoid leukemia

ABSTRACT Introduction: To assess the frequency of allergic reactions to asparaginase (ASP) and possible risk factors for reactions in a cohort of pediatric patients. Method: The study was performed based on retrospective data from patients under acute lymphoid leukemia treatment in a general university hospital located in southern Brazil. Information on patients who used ASP from 2010 to 2017 was collected. Allergic reactions were identified in electronic medical records. Results: Among the 98 patients included in the study, 16 (16.3 %) experienced an allergic reaction to native l-asparaginase (L-ASP). Of the 22 patients (22.4 %) that received only intravenous (IV) administration of l-ASP, 10 (62.5 %) had allergic reactions, while 48 patients (49 %) received intramuscular (IM) administration and 28 (28.6 %) received IV and IM administrations. The occurrence of allergic reactions differed between the groups (p < 0.001), and IV administration was associated with allergic reactions. Association was also observed between the severity of the reaction and the route of administration, with the IM route associated with grade 2 and IV route associated with grade 3. Occurrence of allergic reactions was higher when the commercial formulation of l-ASP, Leuginase®, was used (p = 0.0009 in the analysis per patient and p = 0.0003 in the analysis per administration). Conclusions: The IV administration and commercial Leuginase® presentation were associated with more allergic reactions in the study population, which corroborates the findings in the literature. The IV route was also associated with higher severity of reactions in the present study.

Allergic reactions to asparaginase: retrospective cohort study in pediatric patients with acute lymphoid leukemia.

INTRODUCTION: To assess the frequency of allergic reactions to asparaginase (ASP) and possible risk factors for reactions in a cohort of pediatric patients. METHOD: The study was performed based on retrospective data from patients under acute lymphoid leukemia treatment in a general university hospital located in southern Brazil. Information on patients who used ASP from 2010 to 2017 was collected. Allergic reactions were identified in electronic medical records. RESULTS: Among the 98 patients included in the study, 16 (16.3 %) experienced an allergic reaction to native l-asparaginase (L-ASP). Of the 22 patients (22.4 %) that received only intravenous (IV) administration of l-ASP, 10 (62.5 %) had allergic reactions, while 48 patients (49 %) received intramuscular (IM) administration and 28 (28.6 %) received IV and IM administrations. The occurrence of allergic reactions differed between the groups (p <  0.001), and IV administration was associated with allergic reactions. Association was also observed between the severity of the reaction and the route of administration, with the IM route associated with grade 2 and IV route associated with grade 3. Occurrence of allergic reactions was higher when the commercial formulation of l-ASP, Leuginase®, was used (p =  0.0009 in the analysis per patient and p =  0.0003 in the analysis per administration). CONCLUSIONS: The IV administration and commercial Leuginase® presentation were associated with more allergic reactions in the study population, which corroborates the findings in the literature. The IV route was also associated with higher severity of reactions in the present study.

A novel approach to arthritis treatment based on resveratrol and curcumin co-encapsulated in lipid-core nanocapsules: In vivo studies.

Resveratrol and curcumin are two natural polyphenols extensively used due to their remarkable anti-inflammatory activity. The present work presents an inedited study of the in vivo antioedematogenic activity of these polyphenols co-encapsulated in lipid-core nanocapsules on Complete Freund's adjuvant (CFA)-induced arthritis in rats. Lipid-core nanocapsules were prepared by interfacial deposition of preformed polymer. Animals received a single subplantar injection of CFA in the right paw. Fourteen days after arthritis induction, they were treated with resveratrol, curcumin, or both in solution or loaded in lipid-core nanocapsules (1.75 mg/kg/twice daily, i.p.), for 8 days. At the doses used, the polyphenols in solution were not able to decrease paw oedema. However, nanoencapsulation improved the antioedematogenic activity of polyphenols at the same doses. In addition, the treatment with co-encapsulated polyphenols showed the most pronounced effects, where an inhibition of 37-55% was observed between day 16 and 22 after arthritis induction. This treatment minimized most of the histological changes observed, like fibrosis in synovial tissue, cartilage and bone loss. In addition, unlike conventionally arthritis treatment, resveratrol and curcumin co-encapsulated in lipid-core nanocapsules did not alter important hepatic biochemical markers (ALP, AST, and ALT). In conclusion, the strategy of co-encapsulating resveratrol and curcumin in lipid-core nanocapsules improves their efficacy as oedematogenic agents, with no evidence of hepatotoxic effects. This is a promising strategy for the development of new schemes for treatment of chronic inflammation diseases, like arthritis.