Standardized Supportive Care Documentation Improves Safety of High-Dose Methotrexate Treatment

Abstract

Background High‐dose methotrexate (HD‐MTX) is an essential component of treatment protocols in acute lymphoblastic leukemia, aggressive lymphoma and osteosarcoma. However, delayed MTX clearance may lead to life‐threatening toxicities. Administration of supportive therapy for HD‐MTX is complex and insufficent supportive care increases the risk of MTX toxicity. To improve patient safety we investigated the implementation of a checklist and urine alkalinization protocol in addition to standard supportive care during HD‐MTX therapy. Methods The intervention included individualized patient checklists for control of adequate supportive care for every HD‐MTX treatment cycle and an urine alkalinization protocol for documentation and guidance during urine alkalinization therapy. The impact of these tools on the rate of adverse events (acute renal injury, delayed MTX clearance) was retrospectively assessed in patients treated from April 2017 to April 2019 (intervention group) and compared to patients treated from January 2015 to March 2017 who received standard supportive care for HD‐MTX according to a standard operating procedure (SOP group). Results 118 patients received 414 HD‐MTX cycles in the intervention group compared to 108 patients with 332 treatment cycles in the SOP group. Delayed MTX clearance was observed in 2.6% of treatment cycles in the intervention cohort opposed to 15.2% of cycles in the SOP group. The rate of acute kidney injury was also significantly reduced in the intervention group (6.2. vs. 0.7%). The use of carboxypeptidase as rescue treatment for severe renal impairment and insufficient MTX clearance was necessary in 5 cases in the SOP group and only in 2 cycles within the intervention group. Conclusion The use of standardized documentation for supportive care during HD‐MTX therapy is recommended to minimize the risk of adverse events. Implications for Clinical Practice High‐dose methotrexate (HD‐MTX) is a commonly used treatment in several cancer types. Distinct supportive measures are necessary to minimize the risk of HD‐MTX side effects, which can be life‐threatening. Supportive care consists of certain examinations and interventions prior to starting HD‐MTX and permament alkalinization of the urine, as this greatly increases the elimination of MTX and decreases the risk of kidney injury. Here we report on our findings after implementing a checklist for control of supportive care and a urine alkalinization protocol to optimize urine alkalinization. We observed a significant decrease of side effects by using these supportive care tools in comparison to the standard of care. Therefore we recommend to use a safety checklist and alkalinization protocol in all patients who receive HD‐MTX.