Clinical Study On Drug Concentration And Adverse Effects Of Different High Dose Methotrexate In Treatment Of Childhood Acute Lymphoblastic Leukemia

Objective：The purpose of the present study were to observe the drugconcentration and adverse reactions of different high-dose methotrexate(HD-MTX) infused intravenously for24hours in childhood acute lymphoblasticleukemia（ALL），then provided a reference for the development of individualtreatment programs．Methods： To retrospective analysis clinical data of238case-times ofHD-MTX in64cases of children with ALL. A total of238case-times wereclassified into tow groups according to the dosage of MTX．The group A (161case-times) received MTX5g/m2continuous intravenous infusion over24hoursand the group B (77case-times) received MTX3g/m2continuous intravenousinfusion over24hours．36hours after initiation of MTX infusion，calciumfolinate (CF) was given as rescue．The dosage was adjusted in cases ofinappropriate excretion of MTX．No additional rescue was given when MTXserum concentrations had dropped to less than0.1μmol/L at48hours or laterafter the start of MTX infusion．It was analyzed that the relationships betweenMTX dosage，MTX serum concentrations at48hours and72hours and the incidence and severity of adverse reactions．Results：The MTX serum concentrations at48hours and72hours oftwo different HD-MTX infusion was not significantly different(P＞0.05)．AllMTX plasma concentrations at48hours were in excess of the safeconcentration． The MTX plasma concentration at48hours＞1.0μmol/Laccounted for29.1%，and the MTX concentration at72hours＞0.1μmol/Lmade up62.6%．Gastrointestinal reactions，mucosal damage，bone marrowsuppression，hepatic damage and secondary infection were the common adversereactions after HD-MTX chemotherapy．Skin allergic reactions and drug feverwere rare．And there were no urinary system，nervous system and cardiacfunction damage．The incidence of variety adverse reactions of group A werehigher than group B，but the difference was not statistically significant (P＞0.05)．The incidence and severity of digestive tract reaction and mucosal injuryrelated with MTX plasma concentration at48hours (P＜0.05)．The incidence ofbone marrow inhibited was not significantly dependent on MTX plasmaconcentration at48hours (P＞0.05)， but its severity and MTX plasmaconcentration at48hours had statistically significant correlation (P＜0.05)．Theincidence and severity of allergic skin reactions，liver damage and secondaryinfection were no statistical correlation between MTX plasma concentration at48hours (P＞0.05)．The children whose MTX plasma concentrations at72hours were less than0.1μmol/L had low incidence and mild severity adversereactions．And those whose MTX plasma concentrations at72hours were higherthan0.1μmol/L continued rescue to less than0.1μmol/L. In addition to themucosal damage，the increased incidence and severity of other adverse reactionssuch as gastrointestinal reactions，allergic skin reactions，liver damage，bone marrow suppression and secondary infection were not statistically significant(P＞0.05)．Conclusions：MTX plasma concentration at48hours or later were notassociated with the total dosage of MTX infusion．The incidence and severity ofadverse reactions had no statistically significant correlation to the total dosage ofMTX，but related with48hours MTX plasma concentration． And those whose72hours MTX plasma concentration exceeded0.1μmol/L continued rescue toless than safe concentration．The increased incidence and severity of adversereactions were not statistically significant．With monitoring MTX concentrationsand implementing individualized treatment，the serious adverse reactions can beavoided．...