This study prospectively analyzed the efficacy of very prolonged courses of pegylated Escherichia coli
asparaginase (PEGasparaginase) and Erwinia
asparaginase in pediatric
acute lymphoblastic leukemia (ALL) patients. Patients received 15 PEGasparaginase infusions (2500 IU/m(2) every 2 weeks) in intensification after receiving native E coli
asparaginase in induction. In case of
allergy to or silent inactivation of PEGasparaginase, Erwinia
asparaginase (20 000 IU/m(2) 2-3 times weekly) was given. Eighty-nine patients were enrolled in the PEGasparaginase study. Twenty (22%) of the PEGasparaginase-treated patients developed an
allergy; 7 (8%) showed silent inactivation. The PEGasparaginase level was 0 in all allergic patients (grade 1-4). Patients without
hypersensitivity to PEGasparaginase had serum mean trough levels of 899 U/L. Fifty-nine patients were included in the Erwinia
asparaginase study; 2 (3%) developed an
allergy and none silent inactivation. Ninety-six percent had at least 1 trough level ≥100 U/L. The serum
asparagine level was not always completely depleted with Erwinia
asparaginase in contrast to PEGasparaginase. The presence of
asparaginase antibodies was related to
allergies and silent inactivation, but with low specificity (64%). Use of native E coli
asparaginase in induction leads to high
hypersensitivity rates to PEGasparaginase in intensification. Therefore, PEGasparaginase should be used upfront in induction, and we suggest that the dose could be lowered. Switching to Erwinia
asparaginase leads to effective
asparaginase levels in most patients. Therapeutic
drug monitoring has been added to our ALL-11 protocol to individualize
asparaginase therapy.