Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia.
L-asparaginase (L-ASNase) has been an essential component of multiagent chemotherapy for acute lymphoblastic leukemia in childhood for over 3 decades. There are currently 2 Food and Drug Administration (FDA)-approved formulations of L-ASNase derived from Escherichia coli and 1 non-FDA approved formulation derived from Erwinia chrysanthemi. Modifications in L-ASNase have included pegylation, which decreases drug immunogenicity and increases the half-life, allowing less frequent administration. Although L-ASNase is well-tolerated in most patients and causes little myelosuppression, significant toxicities occur in up to 30% of patients. Hypersensitivity is the most common toxicity of L-ASNase therapy and limits the further use of the drug. Other significant toxicities relate to a reduction in protein synthesis and include pancreatitis, thrombosis, central nervous system complications, and liver dysfunction. The spectrum of common toxicities and the efficacy of different formulations of L-ASNase are presented in this review.
Raetz
Elizabeth A
EA
Division of Pediatric Hematology/Oncology, Department of Pediatrics, New York University School of Medicine, New York, NY 10016, USA. elizabeth.raetz@nyumc.org
Salzer
Wanda L
WL
D000971:Antineoplastic Combined Chemotherapy Protocols; D001216:Asparagine / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D001216:Asparagine