Raetz Elizabeth A, Salzer Wanda L
Division of Pediatric Hematology/Oncology, Department of Pediatrics, New York University School of Medicine, New York, NY 10016, USA.
J Pediatr Hematol Oncol. 2010 Oct;32(7):554-63. doi: 10.1097/MPH.0b013e3181e6f003.
L-asparaginase (L-ASNase) has been an essential component of multiagent chemotherapy for acute lymphoblastic leukemia in childhood for over 3 decades. There are currently 2 Food and Drug Administration (FDA)-approved formulations of L-ASNase derived from Escherichia coli and 1 non-FDA approved formulation derived from Erwinia chrysanthemi. Modifications in L-ASNase have included pegylation, which decreases drug immunogenicity and increases the half-life, allowing less frequent administration. Although L-ASNase is well-tolerated in most patients and causes little myelosuppression, significant toxicities occur in up to 30% of patients. Hypersensitivity is the most common toxicity of L-ASNase therapy and limits the further use of the drug. Other significant toxicities relate to a reduction in protein synthesis and include pancreatitis, thrombosis, central nervous system complications, and liver dysfunction. The spectrum of common toxicities and the efficacy of different formulations of L-ASNase are presented in this review.
30多年来，L-天冬酰胺酶（L-ASNase）一直是儿童急性淋巴细胞白血病多药化疗的重要组成部分。目前有2种经美国食品药品监督管理局（FDA）批准的源自大肠杆菌的L-ASNase制剂，以及1种未经FDA批准的源自菊欧文氏菌的制剂。L-ASNase的改良包括聚乙二醇化，这降低了药物的免疫原性并延长了半衰期，从而减少了给药频率。尽管大多数患者对L-ASNase耐受性良好且很少引起骨髓抑制，但仍有高达30%的患者出现严重毒性。超敏反应是L-ASNase治疗最常见的毒性，限制了该药物的进一步使用。其他严重毒性与蛋白质合成减少有关，包括胰腺炎、血栓形成、中枢神经系统并发症和肝功能障碍。本文综述了L-ASNase常见毒性谱及不同制剂的疗效。
