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Published on: July 20, 2016
Retrospective cohort study monitoring PEG-asparaginase activity in acute lymphoblastic leukemia patients with and
Michael Losasso1, Bruce Bostrom2, Yoav Messinger2
1University of St. Thomas, 2115 Summit Avenue, St. Paul, Minnesota, 55105, USA.
Insights
Silent inactivation of pegaspargase is rare in acute lymphoblastic leukemia (ALL) patients. Routine monitoring of pegaspargase activity is recommended only for patients receiving more than two doses.
Area of Science:
- Oncology
- Pharmacology
Background:
- PEG-L-asparaginase (pegaspargase) is crucial for acute lymphoblastic leukemia (ALL) treatment.
- Allergic reactions and silent neutralizing antibodies can lead to pegaspargase discontinuation.
- Premedication may reduce allergic reactions but its effect on silent inactivation is unknown.
Purpose of the Study:
- To determine the incidence of silent inactivation of pegaspargase.
- To compare the incidence of allergic reactions with and without premedication in ALL patients.
Main Methods:
- Retrospective cohort study of newly diagnosed children and young adults with ALL.
- Monitoring asparaginase activity using a commercial assay after pegaspargase administration.
- Comparing allergic reaction incidence before and after premedication initiation.
Main Results:
- Silent inactivation occurred in 1.7% of patients after the second dose; none after the first dose.
- Premedication showed a non-significant trend towards lower allergic reaction rates (8.3% vs. 17% per patient).
- Premedication did not impact pegaspargase activity.
Conclusions:
- Silent inactivation of pegaspargase is infrequent, especially with intravenous administration.
- Routine monitoring of pegaspargase activity is not necessary for patients receiving two or fewer doses.
- Monitoring is recommended for patients scheduled for more than two pegaspargase doses.
Abstract:
Background: PEG-L-asparaginase (pegaspargase) is a critical component of therapy for children and adults with acute lymphoblastic leukemia (ALL). Allergic reactions, which may occur in up to one third of patients, are the major cause for discontinuation. One study reported lower rates of allergic reactions with premedication. Besides allergy, an unknown number of patients develop silent neutralizing antibodies not associated with allergic reactions. The purpose of this retrospective cohort study was to determine the incidence of silent inactivation of pegasparaginase and compare incidence of allergic reactions with and without premedication. Methods: Using a commercial assay, asparaginase activity was monitored following pegaspargase (2500 units/m 2) in newly diagnosed children and young adults with B- and T-cell ALL from February 2013 to May 2017. The incidence of allergic reactions before and after initiation of premedication in May 2015 was compared. Results: One patient out of 59 (1.7%) had silent inactivation after the second dose. No patient had silent inactivation after the first pegaspargase dose and no standard risk B-cell ALL patients, who received only two pegaspargase doses in combination with oral dexamethasone, had silent inactivation. The incidence of grade 3 or 4 allergic reactions was 3.7% per dose with premedication (methylprednisolone, acetaminophen and diphenhydramine) versus 5.2% without. The incidence per patient with premedication given for most of the doses was 8.3% versus 17% without. These values are not statistically significant. Premedication did not affect pegaspargase activity. Conclusions: Due to the low incidence of silent inactivation with intravenous pegaspargase and the unlikely event patients receiving only two doses of pegasparaginase would receive erwinase for this possible transient silent inactivation, we recommend routine monitoring of pegaspargase activity only in patients scheduled to receive more than two doses.
