Discussion:
We present two patients receiving recombinant Erwinia asparaginase who developed symptomatic hyperammonemia concurrent with robust asparaginase activity levels. Fortunately our patients had relatively minor symptoms, but hyperammonemia can be severe.7,8 These are the first reported cases of hyperammonemia with recombinant Erwinia asparaginase and will hopefully bring awareness to this potentially serious complication. Minimal literature is available regarding appropriate treatment for asparaginase-induced hyperammonemia, and sodium benzoate and arginine have been trialed without success.13 Our experience, coupled with the case series published by Nussbaum and colleagues, support the use of lactulose.9 Interestingly, both of our patients and the patients presented by Nussbaum were all adolescents/young adults.9
Our report has several limitations. First, the latency with which our asparaginase activity levels resulted, in the context of every 48-72 hour dosing, presented a challenge in clinical practice. Second, due to its retrospective nature, we cannot assure ourselves that the ammonia levels were handled appropriately (e.g. placed on ice immediately)—which could falsely elevate the levels.14 However, our institutional laboratory catalog does instruct immediately placing the sample on ice, and the symptoms that our patients reported were consistent with hyperammonemia.
Recombinant Erwinia asparaginase is relatively new, and its use is reserved for patients with hypersensitivity to E. coliasparaginase products. This limited use may explain a lack of data outlining symptomatic hyperammonemia. Secondly, while there are no head-to-head trials, published literature supports that there may be a lower incidence of symptomatic hyperammonemia with Erwinia asparaginase products compared to pegaspargase.6,10 Further research is needed to provide guidance on which patients receiving recombinant Erwinia asparaginase warrant ammonia and asparaginase activity level monitoring and recommended management.
Dr. Kuhn discloses recent participation on an advisory board for Rylaze for Jazz Pharmaceuticals. No other authors have any conflicts of interest.
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