PGY1 Pharmacy Resident Ronald Reagan UCLA Medical Center Los Angeles, California, United States
Poster Abstract:
Background: High-dose methotrexate (HDMTX) is commonly used in the treatment of acute lymphoblastic leukemia, central nervous system lymphoma, and osteosarcoma. Treatment can be complicated by toxicities such as nephrotoxicity, hepatotoxicity, myelosuppression, pneumonitis, and mucositis. Given the associated risks, standard supportive care measures include urine alkalinization, hydration, leucovorin rescue, and plasma methotrexate level monitoring. For patients with delayed methotrexate clearance due to impaired renal function, glucarpidase can be administered within a specified time frame to lower toxic plasma methotrexate concentrations. To date, few studies have evaluated the impact of HDMTX management guidelines. Current literature has demonstrated the benefit and importance of a pharmacy-driven management protocol and provides a basis for further research.
Objective: The purpose of this study was to assess the clinical and financial impact by comparing the differences in outcomes before and after implementation of HDMTX management guidelines at our institution.
Methods: A single-institution, retrospective chart review was performed in adult patients who received HDMTX (≥3.5 g/m2) at UCLA Health. Eligible patients received inpatient treatment between March 1, 2020 and March 31, 2021 (pre-protocol group) or between April 1, 2022 and April 30, 2023 (post-protocol group) at either Ronald Reagan UCLA Medical Center or UCLA Santa Monica Medical Center. The primary outcome was the incidence of grade ≥3 non-hematological adverse events, including acute kidney injury, acute hepatic injury, neutropenia within four weeks of HDMTX administration, pneumonitis, and mucositis. Secondary outcomes included time to methotrexate clearance; methotrexate levels at 24, 36, 48, and 72 hours; time to urine alkalinization (urine pH ≥7.5); time to first dose of leucovorin; rate of appropriate leucovorin adjustments; number of glucarpidase administrations; length of stay; and total cost of the hospital encounter.
Discussion/conclusions: Final results and conclusions are pending depending on completion of data collection and analysis. We hypothesize that there will be a statistically significant decrease in the incidence of grade ≥3 non-hematological adverse events in the post-protocol group compared to the pre-protocol group.
References (must also be included in final poster): Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist. 2016;21(12):1471-1482. Cerminara Z, Duffy A, Nishioka J, Trovato J, Gilmore S. A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration. J Oncol Pharm Pract. 2019;25(1):76-84. Kowalski A, Jaszczur SM, Nguyen-Nadeau M, Merl MY. Assessment of High-Dose Methotrexate Management Guidelines in Adults with Cancer at an Academic Medical Center. J Hematol Oncol Pharm. 2021;11(2):69-73). Jones K, Mohassel L, Cuevo R. Safety and Effectiveness of a Pharmacist-Driven High-Dose Methotrexate Monitoring Protocol at an Academic Medical Center. Blood. 2021;138(1):4572-4574.
