{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:04:07Z","timestamp":1779685447154,"version":"3.53.1"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Very severe aplastic anemia (VSAA) is a life-threatening bone marrow failure syndrome. For patients ineligible for allogeneic hematopoietic stem cell transplantation (HSCT), effective treatments that induce rapid responses remain limited. This case report describes a young VSAA patient who achieved an exceptionally rapid trilineage response to first-line therapy with high-dose romiplostim (ROMI), hetrombopag, and standard immunosuppressive therapy (IST).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 16-years-old male with newly diagnosed VSAA (neutrophils 0.13 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L, platelets 11 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L) declined HSCT due to fertility concerns. He received ROMI (10 \u03bcg\/kg weekly, titrated to 20 \u03bcg\/kg), hetrombopag (7.5 mg daily), and IST (rabbit ATG 3 mg\/kg\/day for 5 days; cyclosporine 3 mg\/kg\/day). A partial trilineage response was achieved by week 9, with transfusion independence for red cells and platelets by week 12. By week 22, he achieved complete remission. After 7 months of follow-up, he remained in complete remission (neutrophils 2.2 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L, hemoglobin 127 g\/L, platelets 160 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L). ROMI has been gradually tapered and is currently administered at 10 \u03bcg\/kg per month. Throughout the treatment period, the patient experienced only grade 1\u20132 nausea and muscle spasms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of high-dose ROMI, hetrombopag, and IST induced a rapid response in this young VSAA patient who refused HSCT. This dual TPO-RA regimen warrants further investigation as a potential first-line option for HSCT-ineligible VSAA patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1793166","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:46:13Z","timestamp":1779684373000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapid early hematological response in a newly diagnosed patient with very severe aplastic anemia: a case report of high-dose romiplostim, hetrombopag and IST combination therapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Liangkui","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Hematology, Shenzhen Hospital of Southern Medical University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shenzhen Hospital of Southern Medical University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbin","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shenzhen Hospital of Southern Medical University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"586.e1","DOI":"10.1016\/j.jtct.2022.05.027","article-title":"Frontline therapy options for adults with newly diagnosed severe aplastic anemia: intensive immunosuppressive therapy plus eltrombopag or matched sibling donor hematopoietic stem cell transplantation?","volume":"28","author":"Huang","year":"2022","journal-title":"Trans Cell Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"348","DOI":"10.3324\/haematol.13829","article-title":"Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study.","volume":"94","author":"Scheinberg","year":"2009","journal-title":"Haematologica."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1080\/16078454.2021.2009646","article-title":"Treatment outcome of 301 aplastic anemia patients in China: a 10-year follow-up and real-world data from single institute experience.","volume":"26","author":"Zhang","year":"2021","journal-title":"Hematology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa2109965","article-title":"Eltrombopag added to immunosuppression in severe aplastic anemia.","volume":"386","author":"Peffault de Latour","year":"2022","journal-title":"N Engl J Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"4448","DOI":"10.1182\/bloodadvances.2024015405","article-title":"Up-front alternative donor HCT in severe Aplastic anemia: gaps and opportunities to translate evidence into practice.","volume":"9","author":"Bhatt","year":"2025","journal-title":"Blood Adv."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3483","DOI":"10.1007\/s00277-024-05910-w","article-title":"Comparison of efficacy of eltrombopag combined with immunosuppression in the treatment of severe aplastic anemia and very severe aplastic anemia: real-world data and evidence.","volume":"103","author":"Li","year":"2024","journal-title":"Ann Hematol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4477","DOI":"10.1007\/s00277-024-05964-w","article-title":"The effect of Hetrombopag combined with conventional treatment on immune function and quality of life in patients with severe aplastic anemia.","volume":"103","author":"Chen","year":"2024","journal-title":"Ann Hematol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1182\/bloodadvances.2023010959","article-title":"Long-term efficacy and safety of romiplostim in refractory aplastic anemia: follow-up of a phase 2\/3 study.","volume":"8","author":"Mitani","year":"2024","journal-title":"Blood Adv."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e562","DOI":"10.1016\/S2352-3026(19)30153-X","article-title":"Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial.","volume":"6","author":"Lee","year":"2019","journal-title":"Lancet Haematol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/bjh.20206","article-title":"Romiplostim with ciclosporin A in patients with aplastic anaemia na\u00efve to immunosuppressive therapy: a phase 2\/3 study.","volume":"207","author":"Lee","year":"2025","journal-title":"Br J Haematol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2514791","DOI":"10.1080\/07853890.2025.2514791","article-title":"Effective treatment of refractory aplastic anemia with romiplostim after failure of multiple thrombopoietin receptor agonists: a single-center retrospective study.","volume":"57","author":"Lin","year":"2025","journal-title":"Ann Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s12185-024-03853-6","article-title":"Expansion effect of romiplostim on hematopoietic stem and progenitor cells versus thrombopoietin and eltrombopag.","volume":"120","author":"Tezuka","year":"2024","journal-title":"Int J Hematol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41375-020-0950-6","article-title":"High-dose romiplostim accelerates hematologic recovery in patients with aplastic anemia refractory to eltrombopag.","volume":"35","author":"Hosokawa","year":"2021","journal-title":"Leukemia."},{"key":"B14","doi-asserted-by":"publisher","first-page":"4003","DOI":"10.1007\/s00277-025-06337-7","article-title":"Predictive factors of romiplostim response in patients with refractory aplastic anemia: data from two clinical trials.","volume":"104","author":"Jang","year":"2025","journal-title":"Ann Hematol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1793166\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:46:20Z","timestamp":1779684380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1793166\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":14,"alternative-id":["10.3389\/fmed.2026.1793166"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1793166","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"article-number":"1793166"}}