Creatinine clearance rate and serum creatinine concentration are related to delayed methotrexate elimination in children with lymphoblastic malignancies

Methotrexate (MTX) is an effective treatment for childhood acute lymphoblastic leukemia (ALL) or Non-Hodgkin lymphoma (NHL); however, toxicity can arise with high doses MTX (HDMTX), especially in patients with delayed MTX elimination.Routine monitoring of plasma MTX concentrations is clinically important, but unfortunately is not always feasible.The aim of this study was to examine the relationship between MTX elimination and renal function to identify parameters that may be useful for predicting delayed MTX elimination in Chinese children with ALL and NHL.A total of 105 children with ALL and NHL were included in the study.Each patient received HDMTX (3 or 5 g/m 2 ) over 24 hours.Plasma MTX concentrations were measured at 24, 48, and 96 hours.Delayed elimination was indicated by plasma MTX concentrations ≥1.0 at 48 hours or ≥0.1 μmol/L at 96 hours.Creatinine clearance rate (CCr) and serum Cr concentrations were measured at 0, 24, and 48 hours.There were 39 patients (37.1%) with delayed MTX elimination.For patients with delayed MTX elimination, the 24 hour plasma MTX concentration was negatively correlated with the 24 hour CCr (P=0.019).The 48 hour plasma MTX concentration was positively correlated with 24 and 48 hour serum Cr concentrations (P=0.001 and P<0.001, respectively), and negatively correlated with the 24 and 48 CCr (both P<0.001).Both MTX concentrations and elimination time decreased with increasing CCr (P<0.05 and P<0.001, respectively).Receiver operating characteristic curves revealed that the best predictors of delayed MTX elimination were 24 hour CCr <100 mL/min (sensitivity: 67.6%; specificity: 72.1%) and 24 hour Cr concentration >36 mmol/L (sensitivity: 64.7%; specificity: 77.4%) (both P < 0.001).CCr and serum Cr concentration may be useful for monitoring plasma MTX concentrations in children receiving HDMTX for ALL and NHL and for predicting delayed MTX elimination.