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Pharmacotherapy. 2018 Jun 4. doi: 10.1002/phar.2145. [Epub ahead of print]

Management of Patients with Acute Methotrexate Nephrotoxicity with High-Dose Leucovorin.

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Renal Division, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, New York.
Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.



Acute kidney injury complicating high-dose methotrexate (HDMTX) therapy increases the risk for severe mucositis, myelosuppression, and death. It is unclear whether high-dose leucovorin and supportive therapy without the use of glucarpidase can reduce toxicity from HDMTX.


The charts of all patients at Memorial Sloan Kettering Cancer Center whose methotrexate (MTX) drug levels at 48 or 72 hours after administration were 10 times or more the toxic level were reviewed between January 2000 and December 2011.


Eighty-eight patients (median age 51 years, range 9-90 years) who received 100 courses of HDMTX were identified. Serum creatinine increased by 2-fold from baseline (median, range 1- to 10-fold), but all patients recovered kidney function. Serum levels of MTX were 69 μmol/L (median, range 2.2-400), 6.9 μmol/L (1.3-64), and 2.0 μmol/L (0.05-26) at 24, 48, and 72 hours, respectively, after administration. A statistically significant correlation existed between MTX levels at 48, 72, 96, and 120 hours after administration but not between 24 and 72 hours or subsequent time points. High-dose leucovorin was given in 81% of courses in accordance with institutional protocols in most cases. Myelosuppression was present in 42%; grade III or higher neutropenia in 29%, and thrombocytopenia in 25%. Infectious complications, oral mucositis, and diarrhea occurred in 21%, 17%, and 6% of patients, respectively. Five deaths occurred, none directly attributed to complications from MTX administration. Seven additional patients received glucarpidase at the discretion of a treating physician during the study period, and results are reported separately.


Patients who had 100 episodes of HDMTX-associated acute kidney injury were treated with a strategy that only included usual supportive measures and high-dose leucovorin. No deaths were directly attributed to complications related to HDMTX. Glucarpidase, an expensive drug, may not be necessary for a significant number of patients.


acute kidney injury; glucarpidase; high-dose methotrexate; kidney toxicity; leucovorin

[Available on 2019-12-04]

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