Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients
Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients
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DOI：
10.1002/cncr.22739
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发表时间：
2007-07-01
期刊：
影响因子：
6.2
通讯作者：
Garratty, George
中科院分区：
文献类型：
--
作者：
Armstrong, Jonathan K.;Hempel, Georg;Garratty, George
背景资料。据报道，在接受治疗的急性淋巴细胞白血病(ALL)患者中，多达三分之一的患者聚乙二醇-天冬酰胺酶(PEG-ASNase)被快速清除，这可能导致他们的治疗无效。此前有报道称，在健康的献血者中，有25%的人出现了抗聚乙二醇抗体(抗-聚乙二醇)。该研究的目的是确定抗聚乙二醇酶是否与快速清除聚乙二醇-天冬氨酸转氨酶有关。方法：该研究重新分析了参加2000年柏林-法兰克福-明斯特研究的儿科患者的储存血清。选择28个样本，其中15个样本在接受PEG-ASNase治疗后未检测到ASNase活性。16名接受未修饰ASNase治疗的受试者也包括在内，其中8名ASNase活性较低。用2种技术检测血清中的抗聚乙二醇抗体：1)血清学，通过聚乙二醇包被的红细胞凝集；2)现在的细胞学，通过10 PM的聚乙二醇珠分析结合免疫球蛋白。结果：在15份来自未检测到ASNase活性的患者血清中，9份用血清学方法检测到抗聚乙二醇抗体，12份用流式细胞仪检测。1例用聚乙二醇-天冬氨酸氨基转移酶治疗后ASNase活性降低(123U/L)的患者检测到抗聚乙二醇抗体。未经改良的天冬氨酸转氨酶治疗患者的血清ASNase活性与抗-PEG值之间无相关性。结论：抗-PEG值的存在与聚乙二醇天冬氨酸氨基转移酶的快速清除密切相关。有必要进行进一步的全面研究，以充分阐明抗聚乙二醇化对聚乙二醇偶联剂的影响。对抗聚乙二醇化药物的筛查和监测可以确定哪些患者适合采用改进的剂量策略或使用非聚乙二醇化药物。
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.