a Children's National Medical Center , Washington , DC , USA.
b Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions , University of Florida , Gainesville , FL , USA.
Leuk Lymphoma. 2019 Jul;60(7):1740-1748. doi: 10.1080/10428194.2018.1542146. Epub 2019 Jan 10.
The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of asparagine, an essential amino acid for ALL cells. The target level of plasma asparaginase activity to achieve asparagine depletion has been between 0.05 and 0.4 IU/mL. COG AALL07P4 examined the asparaginase activity and plasma and CSF asparagine concentration of pegaspargase when given intravenously in the treatment of NCI high risk ALL. Matched plasma asparaginase/asparagine levels of the clearance of 54 doses of pegaspargase given in induction or consolidation demonstrated that all patients who had a plasma asparaginase level >0.02 IU/mL had undetectable plasma asparagine. No difference was observed in CSF asparagine levels associated with matched plasma asparaginase levels of 0.02-0.049 versus 0.05-0.22 IU/mL ( = .25). Our data suggest that a plasma asparaginase activity level of 0.02 IU/mL can effectively deplete plasma asparagine. The data also indicate that the 95% CI for plasma asparagine depletion after a pegaspargase dose is 22-29 days. clinicaltrials.gov identifier NCT00671034.
asparaginase 在急性淋巴细胞白血病 (ALL) 中的疗效取决于天冬酰胺的消耗，天冬酰胺是 ALL 细胞的必需氨基酸。为了实现天冬酰胺的消耗，血浆 asparaginase 活性的目标水平一直在 0.05 到 0.4IU/mL 之间。COG AALL07P4 研究了培门冬酶在 NCI 高危 ALL 治疗中静脉给药时的 asparaginase 活性以及血浆和 CSF 天冬酰胺浓度。在诱导或巩固治疗中，对 54 剂培门冬酶的清除进行了匹配的血浆 asparaginase/天冬酰胺水平研究，结果表明所有血浆 asparaginase 水平 >0.02IU/mL 的患者均检测不到血浆天冬酰胺。与匹配的血浆 asparaginase 水平为 0.02-0.049 与 0.05-0.22IU/mL（ = .25）相比，CSF 天冬酰胺水平没有差异。我们的数据表明，血浆 asparaginase 活性水平为 0.02IU/mL 可以有效消耗血浆天冬酰胺。数据还表明，培门冬酶剂量后 22-29 天血浆天冬酰胺消耗的 95%CI。clinicaltrials.gov 标识符 NCT00671034。
