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Serum creatinine and creatinine clearance for predicting plasma methotrexate concentrations after high-dose methotrexate chemotherapy for the treatment for childhood lymphoblastic malignancies

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Abstract

Purpose

Monitoring of plasma methotrexate (MTX) concentrations allows for therapeutic adjustments in treating childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) with high-dose MTX (HDMTX). We tested the hypothesis that assessment of creatinine clearance (CrCl) and/or serum Cr may be a suitable means of monitoring plasma MTX concentrations.

Methods

All children in the study had ALL or NHL, were in complete remission, and received HDMTX (3 or 5 g/m2)+leucovorin. Plasma MTX concentrations were measured at 24, 48, and 96 h. CrCl was determined at 24 and 48 h. Correlations between 24- and 48-h plasma MTX concentrations and CrCl and serum Cr concentrations were determined. CrCl and serum Cr concentrations were compared over time between children who had delayed and non-delayed MTX elimination.

Results

A total of 105 children were included. There were significant negative correlations between CrCl at 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were significant positive correlations between serum Cr concentrations at both 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were 88 (30.2 %) instances of elimination delay. Children with elimination delay had significantly lower CrCl and higher Cr concentrations at 24 and 48 h compared with children without elimination delay (all p < 0.05).

Conclusion

Our findings suggest that, with further refinement, assessment of renal function may be a useful means of monitoring plasma MTX concentrations during HDMTX for ALL and NHL.

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Acknowledgments

This work was supported in part by the grant from National Natural Science Foundation of China (81100338); Science Technology Department of Zhejian Province, Qianjiang project (2009R10037); and Zhejiang Provincial Natural Scientific Foundation (NoY2100070).

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Correspondence to Yong-min Tang.

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Xu, Wq., Zhang, Ly., Chen, Xy. et al. Serum creatinine and creatinine clearance for predicting plasma methotrexate concentrations after high-dose methotrexate chemotherapy for the treatment for childhood lymphoblastic malignancies. Cancer Chemother Pharmacol 73, 79–86 (2014). https://doi.org/10.1007/s00280-013-2319-2

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