Patient 1:
Patient 1 is an 18-year-old male with very high-risk B-cell ALL. During his third dose of pegaspargase, he experienced a grade 3 hypersensitivity reaction. Though he clinically tolerated a desensitization protocol, resultant asparaginase activity levels were undetectable; therefore, his therapy was modified to substitute recombinant Erwinia asparaginase for all future doses of pegaspargase.
His next scheduled dose of pegaspargase was substituted with 6 doses of recombinant Erwinia asparaginase 50 mg (25 mg/m2) intramuscularly (IM) every 48 hours.11 Within minutes of his fourth dose, he reported feeling nauseous and light-headed. He was treated with a fluid bolus and promethazine. A post-dose ammonia level resulted at 275 µmol/L (upper limit of normal (ULN) 60 µmol/L). Given the symptomatic hyperammonemia with the previous dose, an ammonia level and a nadir serum asparaginase activity (NSAA) were measured prior to the next dose (dose #5 of 6). His pre-dose ammonia level remained elevated at 248 µmol/L, and his NSAA was 0.54 IU/mL (goal NSAA ≥0.1 IU/mL).12 His ammonia level immediately following dose 5 was 321 µmol/L. He reported feeling fatigued and nauseous for about 24 hours after each recombinant Erwinia asparaginase dose.
With the sixth recombinant Erwinia asparaginase dose, the patient received lactulose 20 grams by mouth three times daily (titrated to three soft stools per day) with symptomatic improvement noted within a few days of initiation. Four days after starting lactulose, and with no further asparaginase, ammonia normalized. Due to the high NSAA during the previous course, and to prevent further accumulation of ammonia, the recombinant Erwinia asparaginase dose was decreased by 20% and the frequency was changed to every 72 hours for the next course. Repeat NSAA after the first dose of this new dosing schedule was undetectable, and the dose was increased to 50 mg every 72 hours with a resultant NSAA of 0.34 IU/mL. With the dose adjustment, he has been able to discontinue the lactulose without recurrence of symptomatic hyperammonemia. At the time of publication, the plan for patient 1 is to continue an every 72-hour dosing schedule with NSAA monitoring.