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30 Background: High-dose methotrexate (HDMTX) is administered for the treatment of primary central nervous system (CNS) lymphoma (PCNSL), leptomeningeal metastases, and osteosarcoma, as well as CNS prophylaxis in patients with high-risk lymphoma and leukemia. Treatment is typically administered in an inpatient setting to enable aggressive hydration, urinary alkalinization, and frequent lab monitoring given the risk of acute kidney injury. Multiple pediatric centers have published experiences with outpatient administration of HDMTX. We aim to determine the toxicity rate in adult patients at SKCC receiving HDMTX to identify a population in which to pilot an outpatient HDMTX program. Methods: We performed a retrospective review of all patients receiving inpatient HDMTX at SKCC between January 1, 2018 and October 31, 2019. Results: Seventy-three patients (52% male) with median age of 60 years (range 22-81) received 255 cycles total of HDMTX. Diagnoses include PCNSL/vitreoretinal lymphoma (n=22), diffuse large B-cell lymphoma (n=17), B-cell acute lymphoblastic leukemia (n=16) and other diagnoses (n= 18). Thirty-one cycles were administered as CNS prophylaxis and 224 cycles as treatment, with a median prophylactic dose of 3.5 g/m2 (range 1-3.5) and median treatment dose of 3.5 g/m2 (range 0.25-12). The most common toxicity was acute kidney injury at a median day 3 of the cycle (range 1-7). See the table for details. Conclusions: Acute kidney injury occurred more often in the treatment group compared to prophylaxis group. Of all patients with AKI in the treatment group, 45% had a diagnosis of PCNSL. In the prophylactic group, only 21% of patients (3/14) experienced AKI of which all resolved. Of all AKI events, 90% were Grade 2 and 90% resolved. Based on these results, we plan to pilot an outpatient HDMTX program in patients receiving prophylactic HDMTX to determine its effect on patient quality of life and cost of care. [Table: see text]