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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