ALL患儿L-Asp治疗相关性血浆氨基酸水平变化及其意义(英文)

Contents of L-Asparaginase-Related Amino Acids in the Plasma of Children with ALL

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 detect the contents of L-asparaginase ( L-Asp)-related amino acids in ALL children receiving L-Asp treatment; and to study the relationship between changes in L-Asp contents and clinical efficacy on .ALL. Methods Plasma concentrations of asparagine (Asn), aspartic acid (Aspa), glutamine (Gln) and glutamic acid (Glu) in different stages of L-Asp treatment were measured by the HPLC-FLD method in 20 children with ALL (17 cases of B-ALL and 3 of T-ALL). Results The plasma Asn level after the 1st administration of L-Asp decreased significantly. With the administration of L-Asp according to the induction remission formula of A11-XH99, the Asn level remained low, even to nil level. This status remained for 7 days after cessation of L-Asp, and even 10 days in 15 cases of B-ALL, but the Asn level in all the cases of T-ALL and only 2 cases of B-ALL increased and even returned to nomal 7 days after L-Asp treatment ended. The concentration of Glu after the second and the last administrations of L-Asp increased significantly and it returned to normal on the 7th day after cessation of L-Asp, while the concentration of Aspa increased and failed to return to normal on day 10 after cessation of of L-Asp. The concentration of Gln slightly decreased during the course of treatment with L-Asp, but the difference was not significant compared with that before treatment. Conclusions The Asn level of children with T-ALL after cessation of L-Asp recovers earier than that of children with B-ALL, indicating that it may be helpful for individualization of L-Asp administration in the treatment of ALL on the basis of the immunophenotype of children. The glutaminase activity of L-Asp does not exert effects on the treatment.