A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration.

BACKGROUND: Methotrexate has a wide dosing range. High-dose methotrexate is a dose of 1000 mg/m2 or greater. In the 1970s, the incidence of mortality associated with High-dose methotrexate ranged from 4.6 to 6%. In 2012, the University of Maryland Medical Center implemented a standardized high-dose methotrexate protocol. The purpose of this study was to evaluate whether the institution followed recommendations based on the Bleyer nomogram for the administration of high-dose methotrexate more closely after the implementation of the protocol.

METHODS: In this retrospective chart review, 37 patients received 119 cycles of high-dose methotrexate before the protocol implementation (1 January 2009 through 31 December 2010) and 45 patients received 106 cycles of high-dose methotrexate after protocol implementation (1 January 2013 through 31 December 2014). Patient characteristics, protocol data, and complications were analyzed.

RESULTS: Protocol implementation significantly reduced the deviation of methotrexate level timing at 24, 48, and 72 h: median 7.47 vs. 1.46 h, 7.23 vs. 1.35 h, and 7.00 vs. 1.52 h before and after implementation, respectively (p < 0.0001 for each). The protocol significantly reduced deviation of the first dose of leucovorin administration: median 5.2 vs. 0.675 h before and after implementation, respectively (p<0.0001). After protocol implementation, there was an increase in the use of leucovorin prescriptions written appropriately for patients discharged before methotrexate levels reached a value of ≤0.05 µmol/L.

CONCLUSIONS: Implementation of a protocol for the administration of high-dose methotrexate improved the adherence to consensus recommendations. Further analysis is needed to assess clinical pharmacist involvement and the cost savings implications within this protocol.