急性淋巴细胞白血病患儿大剂量门冬酰胺酶治疗后脑脊液门冬酰胺浓度测定

CEREBROSPINAL FLUID ASPARAGINE CONCENTRATIONS AFTER HIGH-DOSE OF L-AS-PARAGINASE IN CHILDHOOD WITH ACUTE LYMPHOBLASTIC LEUKEMIA

目的：从临床及药代动力学方面，探讨ASP在CNS白血病的药理作用及最佳给药方式。方法：10例ALL，患儿分别4次接受了德国小儿白血病协作组多中心协作治疗方案(COALL-97)中的主要药物ASP(每隔4周-6周1次静脉注射4×10^4U／m^2日本协和发酵工业株式会社生产的L-ASP)的联合化疗。检测静脉注射L-ASP前及给药后第1周，第3周，第4周，第5周CSF中的ASN浓度。结果：CSF中ASN浓度均值分别为：给药前1．894 μmol／L，给药后第1周0．056 μmol／L，第3周0．117 μmol／L，第4周0．212 μmol／L，第5周0．897 μmol／L；每例患儿应用L-ASP后CSF中ASN浓度明显降低(P<0．05)，同时测定CSF中谷氨酰胺浓度在给药前及给药后均无显著变化。结论：1次注射4×10^4U／m^2ASP后能使CSF中ASN浓度降低并持续至第5周后回升。有预防或治疗CNS白血病的作用。

Objective:TheCNSisanimportantsanctuarysiteinchildhoodacutelymphoblasticleukemia(ALL).Cerebrospinalfluid(CSF)asparagineconcentrationreflectsasparaginasesystemicpharmaco-dynamics.Thisstudyistosearchforasaferandmoreeffectivewayofusingasparaginaseasmaindrugincombinationprotocolandtoevaluatedthetimecourseofthecerebrospinalfluid(CSF)asparaginesdepletioninchildrenwithALL.Methods:10childrenwithALLweretreatedincombinationprotocolofCOALL-97/GPOH.TheprotocolisonetimeintravenousinjectionLeunase40×104/m2forevery3~6weeks.CSFas-paraginelevelsweremeasuredbefore,afterintravenousinjectionLeunasein1,3,4,5weeks.Effectsandside蛳effectsofasparaginasewereobservedclinically.Results:L蛳AsparaginewascompletelydepletedafterintravenousinjectionLeunaseCSFasparagineswere0.056infirstweek,0.117μmol/Linthreeweek,0.212μmol/Linfhurdweek,0.897μmol/Linthefiveweek;t-testP<0.05.Levelsofglutaminedidnotchangesignificantlybefore,afterintravenousinjectionLeunase.Thepretreatmentasparaginvalueswerewithinthenormalrange.Conclusion:CSFasparagineconcentrationswaredepletedfrom0~5weekbytheadministrationofhigh-dose4×104U/m2timeasparaginasebyintravenousinjection.