{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:51:42Z","timestamp":1754146302772,"version":"3.41.2"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In the absence of a human leukocyte antigen (HLA)-matched donor, intensive immunosuppressive therapy (IST) combined with unrelated cord blood (IIST-UCB) a salvage treatment option for patients with severe aplastic anemia (SAA) who had failed IST. With advancements in transplantation technology, outcomes of IIST-UCB have improved considerably in recent years. Here, we will focus on the differential effects of IIST-UCB on patient survival and GVHD risk and evaluate its therapeutic efficacy between SAA and VSAA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between August 2004 and May 2024, 115 SAA patients were screened at enrollment. The overall survival (OS) rates and failure-free survival (FFS) rates were evaluated and compared using Kaplan\u2013Meier curves and log-rank tests. Cumulative incidences of cytomegalovirus (CMV), hematopoietic recovery, and Epstein\u2013Barr virus (EBV) were estimated using a competing risk regression model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median age was 16 years (range, 2\u201374). At 6 months, 27 patients (27%) achieved complete response (CR), and 44 patients (44%) achieved partial response (PR). The median period to neutrophil engraftment was 25 days, and to platelet engraftment was 44\u2009days. The 250-day cumulative incidence of hemoglobin recovery was 87.8% (95% CI, 77.7%\u201393.6%). The 100-day cumulative incidence of neutrophil engraftment was 88.5% (95%CI, 80.6%\u201393.3%). The 400-day cumulative incidences of platelet engraftment was 86.7% (95%CI, 77.5%\u201392.4%). The 5-year overall survival was 86.1% \u00b1 6.66%, and the 5-year failure-free survival was 72% \u00b1 8.62% in the cohort. Transplantation-related mortality was 12.5% (95% CI, 7.2%\u201319.4%). No acute or chronic graft-versus-host disease (GVHD) was observed during the entire period. The cumulative incidences of CMV and EBV were 7.18% (95% CI, 3.34%\u201313%) and 16.8 (95% CI, 10.6%\u201324.3%), respectively. The majority of patients exhibited microchimerism and maintained hematopoiesis over the long term. Patients with SAA who received UCB treatment showed significantly higher hematopoietic reconstitution efficiency (<jats:italic>P =<\/jats:italic> 0.004, <jats:italic>P =<\/jats:italic> 0.001, <jats:italic>P =<\/jats:italic> 0.001) and overall survival compared with the VSAA group (<jats:italic>P =<\/jats:italic> 0.028).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data support IIST-UCB as an alternative therapeutic approach for patients with SAA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1622326","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T04:10:36Z","timestamp":1752811836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling new horizons in severe aplastic anemia management: a two-decade study on intensive immunosuppressive therapy combined with unrelated cord blood efficacy"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhipeng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochen","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanjun","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiling","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001347","article-title":"Treg sensitivity to FasL and relative IL-2 deprivation drive idiopathic aplastic anemia immune dysfunction","volume":"136","author":"Lim","year":"2020","journal-title":"Blood."},{"key":"B2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s13045-019-0775-9","article-title":"Who is the best haploidentical donor for acquired severe aplastic anemia? 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