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.
Highlights
PEG-L-asparaginase is a critical component of therapy for children and adults with acute lymphoblastic leukemia (ALL)
Compared with historical controls that received similar therapy, premedication did not significantly reduce the incidence of grade 3 or 4 allergic reactions when measured per patient or per dose of pegaspargase
This decrease of pegaspargase activity occurred after the second dose in a high-risk B-cell ALL patient and resolved with continuation of pegaspargase dosing
Summary
PEG-L-asparaginase (pegaspargase) is a critical component of therapy for children and adults with acute lymphoblastic leukemia (ALL). Its use is hampered by many issues including allergic reactions, silent inactivation, thrombosis, hyperbilirubinemia and pancreatitis[1]. A study in adults with ALL reported allergic reactions in 7.2% of patients when pegaspargase was given concurrently with, or followed by, one week of prednisone[8]. The presence of asparaginase antibodies at end of induction did not appear to alter prognosis in a large multi-center study[11]. This suggests that measuring asparaginase activity is more useful than looking for the presence of antibodies. Prudence suggests that patients who receive premedications should have pegaspargase activity monitored after every dose, due to the possible but unproven concern that premedication will mask allergic reactions and silent inactivation. A consensus panel of experts recommends screening for silent inactivation in all patients undergoing therapy for ALL with asparaginase[14]
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