Hypersensitivity reactions to Escherichia coli –derived polyethylene glycolated–asparaginase associated with subsequent immediate skin test reactivity to E. coli–derived granulocyte colony-stimulating factor

L-asparaginase is a cancer chemotherapeutic agent derived from Escherichia coli. It is effective in treating acute lymphoblastic leukemia (ALL) and other related diseases, but it has been associated with hypersensitivity reactions in from 6% to 43% of patients studied.1 Such reactions can occur after one dose of the drug, but most occur after 2 weeks of daily or thrice weekly therapy.1 The highest prevalence has been observed when L-asparaginase was given as a single agent or when given in higher doses (6000 IU/m2).1 Mechanisms proposed for L-asparaginase reactions include trace endotoxin contamination, IgE-mediated hypersensitivity, IgG or IgM antibody–mediated sensitivity, and complement-mediated reactions.2 Use of intramuscular preparations of L-asparaginase has been associated with a decrease in severe hypersensitivity reactions without loss of efficacy.3 Polyethylene glycolated (PEG)–asparaginase is a further improvement to this because it has a sustained release from tissues and is longer acting. There have been reports of delayed hypersensitivity reactions to intramuscular L-asparaginase3; however, there have been no previously reported cases of anaphylaxis to PEG-asparaginase. Granulocyte colony-stimulating factor (G-CSF) (Filgrastim) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Sargramostim) are hematopoietic growth factors used in treating myelosuppression following cancer chemotherapy. They are structurally distinct, and are derived from different recombinant expression systems: G-CSF from E. coli and GM-CSF from Saccharomyces cerevisiae. Both have been associated with hypersensitivity reactions4, 5; however, they are not believed to be cross-reactive. Because both PEGasparaginase and G-CSF are produced in E. coli, there may be a theoretic concern regarding cross-sensitization in patients who have had life-threatening reactions to one of these agents. We present two cases of anaphylaxis to PEG-asparaginase and discuss our experience with skin testing these patients with G-CSF and GM-CSF.