Dibenedetto S P, Di Cataldo A, Ragusa R, Meli C, Lo Nigro L
Division of Pediatric Hematology and Oncology, University of Catania, Italy.
J Clin Oncol. 1995 Feb;13(2):339-44. doi: 10.1200/JCO.1995.13.2.339.
As part of a study on the pharmacokinetics associated with the administration of asparaginase (ASNase) from Erwinia to the CNS, we determined the levels of asparagine in the CSF of children with acute lymphoblastic leukemia (ALL).
Twenty children received eight standard doses of intramuscular ASNase (10,000 IU/m2) every 3 days as part of induction therapy. In the postremission phase of therapy, the children were randomized to receive either 20 courses of high-dose intramuscular ASNase (25,000 IU/m2) weekly (n = 8) or four courses of standard-dose intramuscular ASNase (10,000 IU/m2) every 3 days (n = 12).
All patients had detectable levels of L-asparagine in the CSF at the time of diagnosis. The levels of L-asparagine in CSF were undetectable in 15 of 20 (75%) and in seven of 19 (36.8%) children 3 and 5 days, respectively, after administration of standard-dose ASNase. After administration of high-dose ASNase, the levels of L-asparagine in the CSF were undetectable in five (62.5%) and two (25%) of eight children after 3 and 5 days, respectively.
In this study 60% to 70% and 25% to 35% of children had complete depletion of L-asparagine from the CSF after 3 and 5 days, respectively, after administration of both schedules of ASNase from Erwinia. In the remaining patients, administration of ASNase may have resulted in a suboptimal antileukemic effect at the CNS level.
作为一项关于欧文氏菌天冬酰胺酶（ASNase）给药至中枢神经系统相关药代动力学研究的一部分，我们测定了急性淋巴细胞白血病（ALL）患儿脑脊液中天冬酰胺的水平。
20名儿童接受了诱导治疗，每3天肌肉注射8剂标准剂量的ASNase（10,000 IU/m²）。在缓解期治疗阶段，这些儿童被随机分为两组，一组每周接受20个疗程的高剂量肌肉注射ASNase（25,000 IU/m²）（n = 8），另一组每3天接受4个疗程的标准剂量肌肉注射ASNase（10,000 IU/m²）（n = 12）。
所有患者在诊断时脑脊液中均可检测到L-天冬酰胺水平。在给予标准剂量ASNase后3天和5天，20名儿童中有15名（75%）和19名儿童中有7名（36.8%）脑脊液中L-天冬酰胺水平检测不到。给予高剂量ASNase后，8名儿童中分别有5名（62.5%）和2名（25%）在3天和5天后脑脊液中L-天冬酰胺水平检测不到。
在本研究中，给予欧文氏菌两种ASNase给药方案后，分别有60%至70%和25%至35%的儿童在3天和5天后脑脊液中的L-天冬酰胺完全耗尽。在其余患者中，ASNase给药可能在中枢神经系统水平导致次优的抗白血病效果。
