Jornal da Leucemia
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Prospective Longitudinal Examination of Hyperammonemia during L-Asparaginase Treatment within 24 Hours after Administration in Childhood Lymphoblastic Malignancies

Marios Paulides, Ronny Jung, Martin Chada, Berthold Lausen, Markus Metzler and Thorsten Langer

L-asparaginase is used in virtually every protocol against acute lymphoblastic malignancies in induction and intensification. In rare cases, patients may develop hyperammonemia encephalopathy as a side-effect, resulting in severe neurologic deterioration and even death. After an index case at our hospital, we conducted prospective longitudinal examination of blood ammonia level kinetics in further six consecutively enrolled patients treated with E.coli L-asparaginase without neurological signs of encephalopathy within 24 hours after administration. All patients developed transient hyperammonemia above the potentially neurotoxic threshold of 60 μmol/l, with peak concentrations being reached 2 hours after L-asparaginase infusion at 144 μmol/l (range 62 -277 μmol/l). A decline to baseline values was observed after 24 hours. We conclude that transient hyperammonemia is frequent in children treated on protocols containing L-asparaginase. A further precipitating event may lead to hyperammonemia encephalopathy with neurologic symptoms. Therefore, all patients with neurologic symptoms during treatment with L-asparaginase should receive metabolic surveillance and blood ammonia examinations in addition to monitoring for infectious or cerebrovascular complications.