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目的检测ALL患儿血浆左旋门冬酰胺酶(L-Asp)治疗过程中相关氨基酸水平变化,探讨这种变化与临床疗效的相关性,为L-Asp的个体化用药提供依据。方法通过HPLC-FLD技术检测20例初治ALL患儿(17例为B-ALL,3例为T-ALL)在L-Asp使用不同时段血浆中门冬酰胺(Asn)、门冬氨酸(Aspa)、谷氨酰胺(Gln)、谷氨酸(Glu)等水平。结果在L-Asp第一次使用后,患儿血浆内Asn显著下降,随着L-Asp的按序使用,患者血浆中Asn始终保持在低水平甚或测不出,有15例B-ALL患儿可持续到L-Asp停用后约7天左右,并在第10天时仍未恢复正常,但全部3例T-ALL患儿却在L-Asp停用后约7天时Asn浓度明显回升甚至达到正常水平,而仅2例B-ALL患儿出现类似情况。与第一次使用L-Asp前1～2 h血浆浓度相比,第二次、最后一次血浆中Glu浓度均显著升高(P<0.05),直至L-Asp停用后第7天血浆浓度才恢复正常;而Aspa浓度则持续升高(P<0.05),到停药后第10天仍未恢复正常;在整个治疗过程中,Gln水平虽略有下降,与治疗前相比并无显著差异。结论L-Asp停用后T-ALL患儿血浆Asn水平较B-ALL患儿恢复快,提示在儿童ALL的治疗中,对于L-Asp的使用,应结合患者免疫学分型,这可能为临床L-Asp个体化用药提供理论依据。而L-Asp的部分谷氨胺酶活性在L-Asp治疗中作用并不显著。
Objective To investigate the changes of plasma amino-acid levels during the treatment of L-Asp in children with ALL, and to explore the correlation between the changes and the clinical curative effect, so as to provide evidence for the individualized use of L-Asp. Methods The plasma levels of Asn, Asp and Asp in 20 cases of newly diagnosed ALL children (17 cases of B-ALL and 3 cases of T-ALL) were detected by HPLC-FLD. Aspa, Gln and Glu. Results After the first use of L-Asp, Asn in plasma decreased significantly, with the sequential use of L-Asp, Asn in patients with plasma levels remained low or even undetectable, 15 patients with B-ALL Children persist until about 7 days after discontinuation of L-Asp and have not yet returned to normal by day 10, but all 3 T-ALL children apparently picked up Asn concentrations even after about 7 days of discontinuation of L-Asp Reached a normal level, while only 2 cases of B-ALL children a similar situation. Plasma concentrations of Glu in the second and last plasma were significantly increased (P <0.05) compared to those in the first 1-2 h prior to the first administration of L-Asp, and plasma concentrations were reduced to day 7 after L-Asp withdrawal (P <0.05). However, the level of Aspa remained unchanged (P <0.05) and remained normal on the 10th day after drug withdrawal. During the whole course of treatment, the level of Gln decreased slightly, which was not significantly different from that before treatment difference. Conclusions Plasma Asn levels in children with T-ALL after discontinuation of L-Asp are recovered faster than those in children with B-ALL, suggesting that the use of L-Asp should be combined with immunologic typing in children with ALL, which may be clinically L-Asp individualized medication to provide a theoretical basis. However, the partial glutamate aminotransferase activity of L-Asp was not significantly affected by L-Asp treatment.