小剂量左旋门冬酰胺酶安全性及药效性的初步研究

目的探讨小剂量(1000 U·m-2·次-1)左旋门冬酰胺酶(L-Asp)应用于小儿急性淋巴细胞白血病(ALL)的安全性与药效性。方法对6例应用常规剂量(5000-10 000 U·m-2·次-1)L-Asp发生过严重不良反应的患儿,改用小剂量L-Asp,观察有无再出现同样或其他的不良反应。随机取5例ALL患儿应用小剂量L-Asp前后的28份血样本,通过反相高效液相色谱分析法检测血浆门冬酰胺(ASN)浓度。结果应用常规剂量L-Asp发生过严重不良反应的患儿,改用小剂量L-Asp后未再发生类似或其他不良反应,应用L-Asp前,患儿血浆ASN水平除例4(4．91μmol/L)外,均高于 5．00 μmol/L,而在应用小剂量L-Asp后的7 d内,患儿血浆ASN的水平除例3(3．70 μmol/L)外,都降到0．50μmol/L以下,即都能被降解到“完全缺乏”或“几乎完全缺乏”水平,并与应用常规剂量组所得结果相近。结论应用小剂量L-Asp治疗小儿ALL,即使对因用常规剂量L-Asp发生过不良反应的患儿也具有肯定的安全性,而且对小儿ALL具有较确切的药效性。

Preliminary study on the safety and pharmacodynamic action of low dose L-asparaginase

OBJECTIVE: To investigate the safety and therapeutic effect of low dose (1000 U/m(2)) L-asparaginase (L-Asp) in the treatment of children with acute lymphoblastic leukemia (ALL). METHODS: Six patients were treated with low dose L-Asp after previously suffered severe side effects from standard dose L-Asp (5000 - 10,000 U/m(2)). Twenty-eight blood samples were obtained randomly from 5 of them. Plasma asparagine concentration was detected by reverse phase-high performance liquid chromatography (RP-HPLC). RESULTS: All the patients treated with low dose L-Asp showed no any toxic symptoms. The plasma asparagine levels in the patients were all above 5 micromol/L except case 4 (4.91 micromol/L) before receiving L-Asp, and were all decreased below 0.5 micromol/L five days after receiving low dose L-Asp, except case 3 (3.70 micromol/L), the results being like that of receiving standard dose L-Asp. CONCLUSION: Low dose L-Asp has definite efficacy for childhood ALL, while avoids serious side effects from standard dose L-Asp.