Correlation study of blood drug concentration and nephrotoxicity on high dose methotrexate therapy in suggestion of diagnosis and treatment of childhood acute lymphoblastic leukemia in the 4th revised edition

Abstract

Objective: To explore the influence of the 4th revised treatment recommendations in childhood acute lymphoblastic leukemia (ALL) on high dose methotrexate(HD-MTX)-induced nephrotoxicity and MTX blood concentrations. Method: The clinical data from 330 ALL children who received 1 242 courses of HD-MTX therapies from September 2012 to November 2016 was collected. The courses were divided into two groups based on the chemotherapies: original scheme group was treated with the 3rd revised regimen, and new scheme group was treated with the 4th revised regimen. The two groups in acute kidney injury (AKI) and MTX blood concentrations were compared. Result: The incidences of AKI with low risk (LR) and intermediate risk (IR) in new scheme group were significantly lower than those in original scheme group (1.3%(3/229) vs. 7.9%(24/303), 4.9%(10/204) vs. 12.8%(26/203), χ(2)=11.831 and 7.888 respectively, both P<0.05). There was no significant difference in the incidence of AKI with high risk (HR) in the two groups (15.2%(10/66) vs. 10.5%(25/237), χ(2)=1.071, P>0.05). The 48h MTX blood concentrations and the interphase from onste to MTX concentrations decreased to the safe level with LR and IR children in new scheme group were significantly lower than those in original scheme group (0.36(0.08-4.00) vs. 0.44(0.06-32.00) μmol/L, 0.49(0.22-33.00) vs. 0.60(0.18-83.00) μmol/L, 3(2-6) vs. 3(2-11) d, 3(2-11) vs. 3(2-19) d, Z=-5.953, -2.658, -4.490 and -4.729 respectively, all P<0.05). The differences with HR were not observed between the two groups (0.61(0.14-36.00) vs. 0.71(0.11-68.00) μmol/L, 3(2-15) vs. 3(2-13) d, Z=-1.465 and -1.179 respectively, both P>0.05). Conclusion: Decreased renal toxicity and acceleration of MTX excretion may occur when childhood ALL with LR and IR were treated with the 4th revised regimen. However, nephrotoxicity and MTX blood concentrations have no significant differences with HR in the two regimens, and close monitoring are necessary.