Safety profile of a single pegylated asparaginase (PEG-ASP) dose in remission induction for acute lymphoblastic leukemia (ALL)

Abstract

The incorporation of pegylated asparaginase (PEG-ASP) in pediatric and adult acute lymphoblastic leukemia (ALL) protocols remains a worldwide therapeutic approach. However the safety profile remains a challenge, and herein we report the toxicity of an intravenous single dose of 1000 IU/m2 PEG-ASP administered in remission induction for adult ALL patients. Thirty-two patients at median diagnostic age of 32 years (median of 19-65) were included in this analysis. Most patients had B-cell lymphoblastic leukemia (n=26; 78%) and 81% of cases were <55 years at study entry. 75% of patients had <30x109/l leukocyte count at diagnosis and median follow-up was 14 months (range 0.8-69). All grade 3/4 adverse events (AEs) after PEG-ASP administration were observed in 24 patients (75%). The most common grade 3/4 AEs were: decreased fibrinogen (58%), increased bilirubin (31%) and increased GGTP (27%). Clinical manifestations related to PEG-ASP were seen in 9 patients and included: abdominal pain (n=6), thrombosis (n=2), diarrhea (n=1) and pancreatitis (n=1). The median time from PEG-ASP administration to first toxic symptoms was 7 days (range 1-19), and there were also 4 (13%) early induction deaths. All deaths were observed in ≥50-year-old patients after a median of 5 days following PEG-ASP (range 1-9). Three of these four patients had massive obesity. While all expired patients had grade 4 neutropenia and thrombocytopenia at the time of death, sepsis was not present. Administration of PEG-ASP in induction remission for ALL patients resulted in a significant, but mostly reversible hepatotoxicity. This PEG-ASP treatment should be administered with caution for older, obese patients.

RETRACTED: Peg-Asparaginase-Associated Pancreatitis in Chemotherapy-Treated Pediatric Patients: A 5-Year Retrospective Study

“…Peg-asparaginase (peg-asp) has a polyethylene glycol molecule conjugated to its E. coli-derived L-asparaginase (l-asp), which could alter its immunogenic property, preventing hypersensitivity and unfavorable immune response (5). With a longer half-life and better patient tolerance, peg-asp is now approved as a first-line asparaginase formulation in ALL chemotherapy regimens (6)(7)(8). Others recommend peg-asp as an alternative treatment for ALL patients who are hypersensitive to native asparaginase (9).…”

N-acetylcysteine vs placebo as adjunctive treatment in paediatric leukaemia: A single blind, randomized controlled trial

“…Mortality rate of leukaemia patients after 5 weeks of therapy were higher in patients with high MDA level. Administration of antioxidants such as vitamin E and N-acetylcysteine (NAC) in ALL children who underwent chemotherapy were related to decrease in hepatotoxicity, haematology complication, need for blood transfusions, and decrease in MDA levels 10 . NAC was used as mucolytic agent in respiratory disease and also as an antidote for hepatotoxicity caused by acetaminophen administration; however, lately NAC has been used as adjunctive treatment in malignancy 11 .…”

Asparaginase-associated pancreatitis in chemotherapy- treated pediatric patients: a five-year retrospective study

“…[5] Moreover, with a longer half-life and better patient tolerance, PEG-Asp is now approved as a first-line Asp formulation in ALL chemotherapy regimens. [6][7][8] This treatment is also effective in patients with other malignant diseases and tumors such as lymphoma and myelosarcoma. [9] Adverse events during chemotherapy have always been a major concern.…”