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The objective of our study was to retrospectively analyze the safety of 2\u00a0cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age &lt;\u200960, albumin &gt;\u200934, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2\u00a0cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1\u00a0cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I\/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I\/II and 18 (16%) grade III\/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III\/IV hematologic toxicities concerned 9 patients with 8 grade III\/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I\/II events. Ambulatory administration of HD-MTX at 3\u00a0g\/m<jats:sup>2<\/jats:sup> without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.<\/jats:p>","DOI":"10.1007\/s00277-020-04341-7","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:36:03Z","timestamp":1613781363000},"page":"979-986","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ambulatory high-dose methotrexate administration as central nervous system prophylaxis in patients with aggressive lymphoma"],"prefix":"10.1007","volume":"100","author":[{"given":"S.","family":"Bernard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Hachon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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