A Pilot Study of Intensified PEG-Asparaginase in High-risk Acute Lymphoblastic Leukemia: Children’s Oncology Group Study AALL08P1

Abstract

AALL08P1 was designed to determine if biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high risk B-precursor lymphoblastic leukemia when given with Children’s Oncology Group hemi-augmented BFM therapy. High Risk-Average (HR-Avg) patients received standard pegaspargase (S-PEG) dosing (6 doses) while High Risk-High (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥ 65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance. Targeted toxicities included allergic reactions, anaphylaxis, pancreatitis, thrombosis, bleeding, central nervous system events and sepsis. AALL08P1 enrolled 104 patients; 54 were classified as HR-Avg and 30 as HR-High after completion of induction therapy. Only 53% (16/30) of the HR-High patients received ≥ 8 total doses of I-PEG and 50% (15/30) took ≤ 49 weeks from start of Consolidation to the initiation of Maintenance. I-PEG did not significantly increase grade 2–5 targeted toxicities. I-PEG was not feasible or safe as defined in AALL08P1. Complete assessment of this regimen was limited due to removal of patients from I-PEG regimen and early closure of the study.

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

“…Adverse events had always been a major concern during the period of chemotherapy. Events such as hyperinsulinemia, hypertriglyceridemia, hypoproteinemia, and coagulation disorders have been reported during asparaginase administration (11). No significant difference was observed in the types of adverse events between l-asp and peg-asp formulation (9).…”

Predictors of hepatotoxicity and pancreatitis in children and adolescents with acute lymphoblastic leukemia treated according to contemporary regimens

“…Six subjects were identified to have DS. Subjects were all treated using mBFM regimens either enrolled on the COG study or following institutional COG‐based protocols for SR B‐ALL (CCG1991, AALL0331, AALL0932), HR B‐ALL (CCG1961, AALL08P1, AALL0232, AALL1131), or T‐ALL (AALL0434, modified AALL0232 [use of dexamethasone for all ages]) . Two patients were BCR‐ABL+ and therapy included the TKI dasatinib, one enrolled on the COG BCR‐ABL‐focused AALL1122 study and one using the AALL0232 backbone.…”

A Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious against Both T- and B-cell Acute Lymphoblastic Leukemias In Vivo

“…Since the debilitating side effects of current L-asparaginases often result in treatment cessation, an event associated with inferior event-free survival (48,54), L-asparaginases with diminished toxicity are highly pertinent to improving ALL treatment outcome. In line with this notion, a recent pilot study, (55) which evaluated an intensified L-asparaginase treatment in a population of high-risk pediatric ALL patients using pegylated Ec A (the current standard of care in the USA with >20-fold higher L-glutaminase activity compared to Er A-TM), had to be aborted due to an unacceptable frequency of adverse-effects. However, since the patients were receiving additional chemotherapeutic drugs, the causative agent behind the increased toxicity cannot be directly linked to the more frequent dosing of the L-asparaginase.…”