Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia

Abstract

Over the past several decades, L-asparaginase, an important component of therapy for acute lymphoblastic leukemia (ALL), has typically been administered intramuscularly rather than intravenously in North America because of concerns regarding anaphylaxis. We evaluated the feasibility of giving polyethylene glycosylated (PEG)-asparaginase, the polyethylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with ALL. Between 2005 and 2007, 197 patients (age, 1-17 years) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-01 and received a single dose of intravenous PEG-asparaginase (2500 IU/m(2)) over 1 hour during remission induction. Serum asparaginase activity more than 0.1 IU/mL was detected in 95%, 88%, and 7% of patients at 11, 18, and 25 days after dosing, respectively. Toxicities included allergy (1.5%), venous thrombosis (2%), and pancreatitis (4.6%). We conclude that intravenous administration of PEG-asparaginase is tolerable in children with ALL, and potentially therapeutic enzyme activity is maintained for at least 2 weeks after a single dose in most patients. This trial was registered at www.clinicaltrials.gov as #NCT00400946.

Efficacy and Tolerance of Pegaspargase-Based Chemotherapy in Patients with Nasal-Type Extranodal NK/T-Cell Lymphoma: a Pilot Study

“…A polyethylene glycol-modified version of L-Asp, pegaspargase (PEG-Asp), was developed in the 1990s with the aim of reducing its immunogenicity (Alfieri et al, 1995). PEG-Asp appears to be safe and effective in patients with acute lymphoblastic leukemia (ALL) (Dinndorf et al, 2007;The Cooperation Group of Phase II Clinical Trial of PEG-Asp, 2008;Silverman et al, 2010); however, the safety and potential efficacy of PEG-Asp in patients with ENKL was not systematically evaluated for future design of relevant clinical trials.…”

L-asparaginase-based regimen as a first-line treatment for newly diagnosed nasal type extranodal natural killer cell/T-cell lymphoma

“…The incidence of allergic reactions in patients who were treated with L-asparaginase has been reported to be 30% (38). Studies have reported that pegaspargase therapy had a similar efficacy to L-asparaginase as a treatment in children with acute lymphoblastic leukaemia (39,40).…”

The coagulopathy and thrombotic risk associated with L-Asparaginase treatment in adults with acute lymphoblastic leukaemia

“…23 Children treated on the DFCI consortium protocol 05-01 received a single dose of intravenous polyethylene glycol-L-Asp and venous thrombotic events occurred in 4 (2%) of patients, 2 being in the CNS. 24 …”