Acute metabolic encephalopathy in two patients treated with asparaginase and ondasetron

Abstract

The most common adverse events Grade III reported with clofarabine are febrile neutropenia, anorexia, and nausea, observed in about 10% of heavily pretreated patients [3]. Our patient experienced more severe events but no unmanageable toxicity and was able to receive further chemotherapy for a second transplantation providing a new complete remission.In conclusion, this report highlights the efficacy of clofarabine in high-risk leukemia. Above all, it suggests that, if clofarabine administration in the setting of end-stage renal failure may carry significant life-threatening risks, it can be considered whether adequate removal of the drug is provided by CVVHD. The relationship between clofarabine plasma concentration and both efficacy and toxicity remains to be elucidated. Further studies on clofarabine pharmacokinetics in the setting of severe renal impairment are needed to develop appropriate guidelines in this situation.

Plasma ammonia concentration after L‐asparaginase therapy in 27 dogs with high‐grade lymphoma or leukemia

“…Hyperammonemic encephalopathy has been documented in people treated with several chemotherapy agents including cytarabine, vincristine, etoposide, L‐asp, cyclophosphamide, 5‐fluorouracil, and sunitinib . L‐asp has been reported to cause hyperammonemia in people with acute lymphoblastic leukemia and lymphoma . Two mechanisms of action have been described.…”

“…First, asparagine is deaminated by asparaginase, which leads to the breakdown products of ammonia and aspartic acid, and thus accumulation of ammonia in the plasma. Glutamine metabolism is also diverted to asparagine synthesis, which is immediately deaminated by asparaginase, which leads to ammonia production . Second, asparaginase has glutaminase activity that metabolizes glutamine into glutamic acid and ammonia by the same deamination process.…”

“…Second, asparaginase has glutaminase activity that metabolizes glutamine into glutamic acid and ammonia by the same deamination process. The urea cycle likely becomes overloaded by the excess ammonia production, leading to hyperammonemia . When serum ammonia concentrations are sufficiently increased, cerebral edema, increased intracranial pressure, seizures, coma, and death can occur.…”

“…[12][13][14][15][16] L-asp has been reported to cause hyperammonemia in people with acute lymphoblastic leukemia and lymphoma. 13,17 Two mechanisms of action have been described. First, asparagine is deaminated by asparaginase, which leads to the breakdown products of ammonia and aspartic acid, and thus accumulation of ammonia in the plasma.…”

“…Glutamine metabolism is also diverted to asparagine synthesis, which is immediately deaminated by asparaginase, which leads to ammonia production. 13,17 Second, asparaginase has glutaminase activity that metabolizes glutamine into glutamic acid and ammonia by the same deamination process. The urea cycle likely becomes overloaded by the excess ammonia production, leading to hyperammonemia.…”