Asparaginase is critical in the treatment of acute lymphoblastic leukemia (ALL). Treatment cessation due to asparaginase hypersensitivity is associated with lower event-free survival. A formulation of asparaginase encapsulated in erythrocytes (eryaspase) was created to maintain asparaginase treatment following hypersensitivity. The safety and effectiveness of eryaspase were examined in 55 patients (aged 1–45 years; median: 6.1 years) with non-high-risk ALL and hypersensitivity to asparaginase conjugated with polyethylene glycol in NOR-GRASPALL 2016 (PEG-asparaginase). In two Nordic/Baltic therapy regimens, eryaspase (150 u/kg) was planned to finish the targeted course of asparaginase (1–7 doses). 

About 49 patients (96.1%) had asparaginase enzyme activity (AEA) ≥100 iu/l 14 ± 2 days after the first eryaspase infusion [median AEA 511 iu/l; interquartile range (IQR), 291–780], whereas six patients (66.7%) had AEA ≥100 iu/l 14 ± 2 days after the fourth infusion (median AEA 932 iu/l; IQR, 496–163). Following the initial injection, the mean terminal half-life of eryaspase was 15.3+15.5 days. Few asparaginase-related side events were observed; five individuals (9.1%) exhibited clinical allergies due to enzyme inactivation. In 50 patients, replacement treatment was completed (90.9%). Eryaspase was well tolerated, and after the first infusion, most patients had AEA levels above the therapeutic goal. The eryaspase half-life verified that a 2-week timetable is adequate.