Among patients with lymphoma, the use of high-dose methotrexate (HDMTX) may lead to a greater risk of acute kidney injury (AKI), intensive care unit (ICU) admission, and death within 30 days, according to research published in JCO Oncology Practice.

HDMTX is defined as therapy dosage of at least 500 mg/m2 and is a mainstay of lymphoma treatment because of its ability to penetrate the central nervous system, potentially leading to a greater chance of response.

However, adverse events such as AKI, which are linked with elevated MTX levels, correlate with clinical outcomes, including morbidity and mortality. For this retrospective study, researchers evaluated for any link between elevated MTX levels and AKI, ICU admission, length of stay (LOS), and survival among patients with lymphoma treated with MTX.

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Overall, data from 642 patients with lymphoma comprising 2804 MTX cycles were included. Among these, 2364 cycles included 48-hour MTX levels of less than 1.28 mu-mol/L, while 441 cycles included 48-hour MTX levels of more than 1.28 mu-mol/L, which was determined to be a critical threshold on later AKI analysis. Furthermore, 78% of cycles were in patients with central nervous system lymphoma.

AKI was noted in 19.1% of patients; grade 2 or worse AKI was reported in 21% of cases. Elevated 48-hour MTX levels were associated with higher rates of AKI, ICU admission, and 30-day mortality. Median LOS was also higher among patients with elevated 48-hour MTX levels (P <.001).

“In conclusion, there was a significantly increased rate of AKI, ICU admission, prolonged LOS, and 30-day mortality with higher 48-hour MTX levels,” the authors wrote. “Complications of HDMTX are significantly increased with elevated 48-hour MTX levels, particularly once the threshold of [more than 1.28 mu-mol/L] is reached.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


O’Donoghue DF, Truong HL, Finnes HD, et al. High-dose methotrexate in patients with lymphoma: predictors of a complicated course. JCO Oncol Pract. Published online October 14, 2022. doi:10.1200/OP.22.00182