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.