Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866).

Kurtzberg, Joanne; Asselin, Barbara; Bernstein, Mark; Buchanan, George R; Pollock, Brad H; Camitta, Bruce M

Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866).

dc.contributor.author	Kurtzberg, Joanne
dc.contributor.author	Asselin, Barbara
dc.contributor.author	Bernstein, Mark
dc.contributor.author	Buchanan, George R
dc.contributor.author	Pollock, Brad H
dc.contributor.author	Camitta, Bruce M
dc.date.accessioned	2022-03-23T19:38:08Z
dc.date.available	2022-03-23T19:38:08Z
dc.date.issued	2011-12
dc.date.updated	2022-03-23T19:38:07Z
dc.description.abstract	Background Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native Escherichia coli L-asparaginase was conjugated to polyethylene glycol (PEG) to formulate PEG-L-asparaginase, a preparation with decreased immunogenicity and increased circulating half-life. In early trials, PEG-L-asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product. Methods The Pediatric Oncology Group conducted a phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse. All patients (n=76) received standard doses of vincristine and prednisone. Nonhypersensitive patients (n=34) were randomized to receive either PEG-L-asparaginase of 2500 IU/m/dose intramuscularly on days 1 and 15 (treatment I) or native E. coli asparaginase of 10,000 IU/m/dose intramuscularly on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (treatment II). Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase (n=42). Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients. Response and toxicity were scored using conventional criteria. Results The complete response rate for the total study population was 41%. There was no difference in complete response between patients randomized to PEG (47%) and native asparaginase (41%). PEG was well tolerated even in patients with prior allergic reactions to native asparaginase. PEG half-life was shorter in patients with prior allergy. Conclusions PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase.
dc.identifier	00043426-201112000-00008
dc.identifier.issn	1077-4114
dc.identifier.issn	1536-3678
dc.identifier.uri	https://hdl.handle.net/10161/24662
dc.language	eng
dc.publisher	Ovid Technologies (Wolters Kluwer Health)
dc.relation.ispartof	Journal of pediatric hematology/oncology
dc.relation.isversionof	10.1097/mph.0b013e31822d4d4e
dc.subject	Bone Marrow
dc.subject	Humans
dc.subject	Drug Hypersensitivity
dc.subject	Recurrence
dc.subject	Polyethylene Glycols
dc.subject	Vincristine
dc.subject	Prednisone
dc.subject	Asparaginase
dc.subject	Escherichia coli Proteins
dc.subject	Antineoplastic Combined Chemotherapy Protocols
dc.subject	Antibodies
dc.subject	Treatment Outcome
dc.subject	Adolescent
dc.subject	Child
dc.subject	Child, Preschool
dc.subject	Infant
dc.subject	Female
dc.subject	Male
dc.subject	Precursor Cell Lymphoblastic Leukemia-Lymphoma
dc.title	Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866).
dc.type	Journal article
duke.contributor.orcid	Kurtzberg, Joanne\|0000-0002-3370-0703
pubs.begin-page	610
pubs.end-page	616
pubs.issue	8
pubs.organisational-group	Duke
pubs.organisational-group	School of Medicine
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Pathology
pubs.organisational-group	Pediatrics
pubs.organisational-group	Duke Cancer Institute
pubs.organisational-group	Institutes and Provost's Academic Units
pubs.organisational-group	Initiatives
pubs.organisational-group	Duke Innovation & Entrepreneurship
pubs.organisational-group	Pediatrics, Transplant and Cellular Therapy
pubs.publication-status	Published
pubs.volume	33