Purpose Asparaginase is an essential component of pediatric acute lymphoblastic leukemia (ALL) therapy. with a common regimen. Both patients developed hypersensitivity reactions to PEGylated asparaginase and asparaginase early in treatment and they were challenged with native asparaginase. Serum samples were collected for estimating the pharmacokinetic parameters of each patient during native asparaginase therapy. Results Challenges with native asparaginase were successful and asparaginase serum concentrations above therapeutic levels were achieved in both patients. Conclusions These two cases suggest that some patients can be given native asparaginase after hypersensitivity reactions to PEGylated asparaginase and achieve therapeutic concentrations of the drug in NBP1 serum. Epidermal Growth Factor Receptor Peptide (985-996) asparaginase that has a half-life of about a week whereas the native asparaginase (Elspar) and asparaginase (Erwinase) have a half-life of 1 1.3 days and 0.65 days respectively [1 4 5 Asparaginase-induced hypersensitivity reactions can decrease exposure to asparaginase. Hypersensitivity reactions to asparaginase can be as frequent as 63% and patients with reactions to asparaginase have been reported to have faster drug clearances compared to patients that did not have reactions [6 7 Furthermore patients that develop neutralizing antibodies to asparaginase even in the absence of a clinical reaction may have sub-therapeutic serum concentrations due to an accelerated asparaginase clearance [1 2 8 Neutralizing antibodies generated against the native preparation have been shown to cross-react with Oncaspar asparaginase but not with Erwinase asparaginase . Patients with low asparaginase exposure due to toxicities have been reported to have worse outcomes . Therefore substituting a different preparation of asparaginase after a hypersensitivity reaction or after the detection of neutralizing antibodies can extend asparaginase therapy and possibly improve patient outcome. In clinical trials PEGylated asparaginase has been associated with a decreased frequency of hypersensitivity  and Oncaspar is usually approved for use in patients who develop allergies to native asparaginase. asparaginase is generally the first choice to use in patients who react to Epidermal Growth Factor Receptor Peptide (985-996) primary treatment with Oncaspar but some of these patients subsequently develop allergies to asparaginase. It is unknown whether patients Epidermal Growth Factor Receptor Peptide (985-996) with past hypersensitivity reactions to Oncaspar asparaginase will cross-react to Elspar asparaginase. Herein we report successful challenges using Elspar in two pediatric ALL patients with previous hypersensitivity reactions to both Oncaspar and Erwinase preparations of asparaginase. Asparaginase serum concentrations above therapeutic levels were achieved in both patients a finding suggesting that selectedpatients with Oncaspar hypersensitivities may continue asparaginase therapy with Elspar asparaginase without cross-reactivity. Case Reports The two patients included in this case report were diagnosed with B-precursor ALL at St. Jude Children’s Research Hospital. Patient A was enrolled on the Total XVI acute leukemia protocol  and Patient B was not enrolled on a clinical trial but did provide consent for comparable treatment Epidermal Growth Factor Receptor Peptide (985-996) regimen and asparaginase serum steps. Table 1 summarizes the pertinent characteristics of the two patients. Oncaspar (3 0 IU/m2 IV) was given at day 3 of remission induction in both patients. Table 1 Patient characteristics Patient A tolerated the first dose of Oncaspar during induction but reacted to the second dose of Oncaspar given during week 1 of continuation (Physique 1A and Supplemental Table 1). The patient had a grade 3 reaction with symptoms including urticaria and difficulty breathing. She was then given Erwinase (42 0 IU/m2 per dose) but developed a grade 3 hypersensitivity reaction to the second dose of Erwinase. The symptoms of the second reaction included itchy eyes bronchospasm with wheezing and difficulty breathing. She was challenged with intravenous Elspar during reinduction I treatment (39 0 IU/m2 per dose) with hydrocortisone (200 mg PO) and diphenhydramine (50 mg.