{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:39:31Z","timestamp":1792269571808,"version":"4.4.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Hypoplastic myelodysplastic syndrome (MDS) often overlaps clinically with aplastic anemia and frequently involves clonal hematopoiesis. Thrombopoietin receptor agonists (TPO\u2010RAs), including eltrombopag, are increasingly used to treat cytopenias in hypoplastic marrow failure syndromes; however, their long\u2010term effects on clonal dynamics and marrow fibrosis remain incompletely defined. We report a case of\n                      <jats:italic>ASXL1<\/jats:italic>\n                      \u2010 and\n                      <jats:italic>TET2<\/jats:italic>\n                      \u2010mutated hypoplastic MDS, initially managed as aplastic anemia, in which eltrombopag therapy was associated with a biphasic clinical course. Hematologic parameters initially improved with reduced transfusion requirements; however, prolonged exposure was followed by progressive marrow fibrosis (MF\u20102 to MF\u20103), worsening cytopenias, and expansion of a minor paroxysmal nocturnal hemoglobinuria (PNH) clone. Serum lactate dehydrogenase levels increased in parallel with fibrosis progression. After eltrombopag discontinuation, the patient achieved transfusion independence within 3 months and substantial regression of marrow fibrosis, accompanied by recovery of marrow cellularity exceeding the pretreatment baseline. Longitudinal molecular analysis demonstrated modest fluctuations in variant allele frequencies without evidence of overt unidirectional clonal progression. The temporal association between fibrosis progression and hematologic deterioration, together with sustained improvement after drug withdrawal, suggests that eltrombopag may have contributed to treatment\u2010associated microenvironmental remodeling that constrained hematopoiesis after an initial stimulatory phase. This case suggests that eltrombopag\u2010associated marrow fibrosis may be reversible even in the presence of clonal hematopoiesis, and that clinical worsening during TPO\u2010RA therapy does not necessarily indicate irreversible clonal evolution. Careful reassessment of marrow morphology, clonal dynamics, and treatment\u2010related niche perturbation may be warranted in patients with hypoplastic MDS who deteriorate during TPO\u2010RA therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>The authors have confirmed clinical trial registration is not needed for this submission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jha2.70393","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:49:55Z","timestamp":1790153395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reversible Eltrombopag\u2010Associated Bone Marrow Fibrosis With Hematologic Recovery After Drug Withdrawal in\n                    <i>ASXL1<\/i>\n                    \u2010Mutated Hypoplastic Myelodysplastic Syndrome: A Case Report"],"prefix":"10.1002","volume":"7","author":[{"given":"Kyoko","family":"Yoshihara","sequence":"first","affiliation":[{"name":"Department of Hematology Hyogo Medical University School of Medicine  Nishinomiya Japan"},{"name":"Department of Transfusion Medicine and Cellular Therapy Hyogo Medical University Hospital  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hyogo Medical University School of Medicine  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Nannya","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology The Institute of Medical Science The University of Tokyo  Tokyo Japan"},{"name":"Department of Pathology and Tumor Biology Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Samori","sequence":"additional","affiliation":[{"name":"Department of Hematology Hyogo Medical University School of Medicine  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naru","family":"Tomigaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Hyogo Medical University School of Medicine  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Hematology Hyogo Medical University School of Medicine  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Ohe","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hyogo Medical University School of Medicine  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Hematology Hyogo Medical University School of Medicine  Nishinomiya Japan"},{"name":"Department of Transfusion Medicine and Cellular Therapy Hyogo Medical University Hospital  Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414799"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201005\u2010574889"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018879536"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10245332.2015.1106815"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20108722\u20105\u201012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.4938"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200931"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(17)30012\u20101"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102005\u201006\u20102485"},{"issue":"9","key":"e_1_2_10_11_1","first-page":"892","article-title":"Reference Guide for the Treatment of Aplastic Anemia: Key Points of the 2022 Revision","volume":"64","author":"Yamazaki H.","year":"2023","journal-title":"Rinsho Ketsueki Japanese Journal of Clinical 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