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Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (<jats:italic>n<\/jats:italic>\u00a0=\u2009315) or without EPAG (<jats:italic>n<\/jats:italic>\u00a0=\u2009206) across 11 studies with multiyear follow\u2010up (3.6 vs. 8.5\u2009years, respectively). Duration of EPAG exposure correlated with ferritin reduction (<jats:italic>p<\/jats:italic>\u00a0=\u20094\u00a0\u00d7\u200910<jats:sup>\u221214<\/jats:sup>) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first\u2010order kinetics with faster clearance (half\u2010life 15.3\u00a0months) compared with historical responders (47.5\u00a0months, <jats:italic>p<\/jats:italic>\u00a0=\u20098\u00a0\u00d7\u200910<jats:sup>\u221210<\/jats:sup>). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron\u2010deficiency anemia mimicking relapse, responsive to iron supplementation.<\/jats:p>","DOI":"10.1002\/ajh.26543","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T14:10:43Z","timestamp":1647871843000},"page":"791-801","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Long\u2010term eltrombopag for bone marrow failure depletes iron"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-8568","authenticated-orcid":false,"given":"David J.","family":"Young","sequence":"first","affiliation":[{"name":"Translational Stem Cell Biology Branch National Heart, Lung, and Blood Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7110-1242","authenticated-orcid":false,"given":"Xing","family":"Fan","sequence":"additional","affiliation":[{"name":"Translational Stem Cell Biology Branch National Heart, Lung, and Blood Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-5926","authenticated-orcid":false,"given":"Emma M.","family":"Groarke","sequence":"additional","affiliation":[{"name":"Hematology Branch National Heart, Lung, and Blood Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2974-7701","authenticated-orcid":false,"given":"Bhavisha","family":"Patel","sequence":"additional","affiliation":[{"name":"Hematology Branch National Heart, Lung, and Blood Institute, NIH  Bethesda Maryland 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