Correlation of L-asp Activity, Anti-L-asp Antibody, Asn and Gln With Adverse Events Especially Anaphylaxis Risks in PEG-asp-Contained Regime Treated Pediatric ALL Patients

Abstract

Objective: This study aimed to investigate the correlation of L-asparaginase (L-asp) activity, anti-L-asp antibody, asparagine and glutamine levels with the risks of adverse events (AEs), especially anaphylaxis, in pediatric acute lymphoblastic leukemia (ALL) patients who underwent polyethylene glycol-conjugated L-asp (PEG-asp)-contained treatment. Methods: Plasma samples were collected from 91 pediatric ALL patients who underwent PEG-asp-contained treatment on the 7th day after drug administration. Plasma L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level were detected. Meanwhile, AEs related to PEG-asp administration were recorded. Results: AEs occurred in 13 (14.3%) patients, among which 7 (7.7%) patients had anaphylaxis, while another 6 patients had non-anaphylaxis AEs (including 4 (4.4%) patients who had acute pancreatitis, 1 (1.1%) patient who had abdominal pain and diarrhea, as well as 1 (1.1%) patient who had nausea and vomiting). L-asp activity was decreased, while asparagine and glutamine levels were increased in patients with AEs compared to patients without AEs, and ROC curves showed that they were correlated with higher AEs risk. Notably, further analyses revealed that L-asp activity, anti-L-asp antibody, asparagine and glutamine levels were highly correlated with anaphylaxis risk, but they were not associated with the risk of non-anaphylactic AEs. Conclusion: The measurement of L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level might assist the prevention of anaphylaxis-related AEs in pediatric ALL patients who underwent PEG-asp-contained treatment.

Comment on “Correlation of L-asp Activity, Anti-L-asp Antibody, asn and gln with Adverse Events Especially Anaphylaxis Risks in PEG-asp-Contained Regime Treated Pediatric ALL”

“… 3 Wu et al suggested, however, that glutamine level might assist the prevention of anaphylaxis-related AEs. 1 It is remarkable that these authors did find glutamine depletion, how could this phenomenon be explained? What was the role and the influence of day 7 post-infusion measurement on the glutamine level in this clinical study?…”

“…I have read with great interest the publication by Wu et al 1 In the context of the Chinese Children's Cancer Group (CCCG)-ALL-2015 protocol, they studied the plasma L-asp activity/anti-L-asp antibody/asparagine/glutamine levels of 91 pediatric ALL patients who underwent PEG-asp-contained treatment on the seventh day after drug administration. Very recently, this CCCG-ALL-2015 protocol was used in an open-label, multicenter, randomized, phase 3, non-inferiority trial which involved twenty major medical centers across China.…”

“… 2 Wu et al suggested that the measurement of L-asp activity/anti-L-asp antibody/asparagine/glutamine levels might assist the prevention of anaphylaxis-related AEs in pediatric ALL patients who underwent PEG-asp-contained treatment. 1 Although this clinical study is of interest, some important questions can be raised, which I address below.…”

“… 6 Wu et al only studied the induction phase. 1 Kloos et al concluded, however, that anti-PEG and anti-SS-linker antibodies predominantly play a role in the immunogenic response to PEGasparaginase during induction. 6 Of interest, these authors suggest that switching to native Escherichia coli asparaginase would be an option for adequate treatment.…”

Author Response: Correlation of L-asp Activity, Anti-L-asp Antibody, Asn and Gln with Adverse Events Especially Anaphylaxis Risks in PEG-asp-Contained Regime Treated Pediatric ALL Patients

“…Sustainably monitoring of L-asp activity would be decided by physicians according to patients’ individual condition, but not the way reported in this study. In addition, as mentioned in the Discussion Section, 3 the sustainably monitoring of L-asp activity, anti-L-asp antibody, Asn and Gln levels at multiple time points is still proceeding now.…”