期刊
CANCER
卷 110, 期 1, 页码 103-111出版社
WILEY
DOI: 10.1002/cncr.22739
关键词
lymphoblastic leukemia; antibody; poly(ethylene glycol); asparaginase medac; PEG-asparaginase; Oncaspar
类别
资金
- NHLBI NIH HHS [HL 15722, HL 70595, HL 65637] Funding Source: Medline
BACKGROUND. Rapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase) has been reported for up to one-third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti-PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti-PEG was associated with rapid clearance PEG-ASNase. METHODS. The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin-Frankfurt-Muenster 2000 studies. Twenty-eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG-ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti-PEG using 2 techniques: 1) serology, by agglutination of PEG-coated red blood cells; 2) now cytometry, by analysis of 10 pm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG-ASNase-treated patients with undetectable ASNase activity, anti-PEG was detected in 9 by serology and in 12 by flow cytometry. Anti-PEG was detected in 1 PEG-ASNase-treated patient with lower ASNase activity (123 U/L). No relation was observed between anti-PEG and serum ASNase activity for patients treated with unmodified ASNase. CONCLUSIONS. The presence of anti-PEG was very closely associated with rapid clearance of PEG-ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents. Screening and monitoring for anti-PEG may allow identification of patients for whom a modified dosing strategy or use of a non-PEGylated drug would be appropriate.
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