{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T06:09:22Z","timestamp":1772431762515,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"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>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Steroid-refractory (SR) hepatic acute graft-versus-host disease (aGVHD) remains a life-threatening complication following allogeneic hematopoietic stem cell transplantation, characterized by limited responsiveness to both first- and second-line therapies and an overall poor prognosis. This study aimed to evaluate the efficacy and safety of cyclophosphamide (CTX) as a salvage treatment for SR- hepatic aGVHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 50 patients with SR-hepatic aGVHD who underwent CTX treatment were retrospectively included in the analysis. Seventeen patients (34.0%) received CTX as second-line therapy, whereas the majority (n=33, 66.0%) were administered CTX as salvage therapy following failure of prior second-line interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall response rate (ORR) at day 28 was 70.0%, with a durable ORR of 66.0% at day 56. Patients with the hepatitic variant of aGVHD showed a superior response compared to those with the classic variant (complete response: 6 of 8 [75.0%] vs. 14 of 42 [33.3%], P = 0.042). The probabilities of overall survival (OS) and nonrelapse mortality (NRM) at 3 years after CTX treatment were 36.9% (95% CI, 24.8%\u201354.9%) and 56.5% (95% CI, 41.4%\u201371.6%). Using propensity score matching (PSM), we compared 35 patients receiving CTX with 35 BAT (best available treatment) controls during the same study period. CTX initiation occurred later than BAT (median line: 3 vs 2, P &amp;lt; 0.001). Response rates and survival outcomes were comparable between two groups and CTX demonstrated consistent efficacy even when used as later-line therapy. Additionally, CTX did not significantly increase the risk of adverse events compared to the BAT group up to day 28. The most common adverse events in both groups were neutropenia (71.4% in the CTX group vs. 62.9% in the BAT group, P = 0.445), anemia (68.6% vs. 60.0%, P = 0.454), and cytomegalovirus infection (51.4% vs. 45.7%, P = 0.632).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that CTX is a promising and well-tolerated treatment option for patients with SR-hepatic aGVHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1678723","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T05:20:54Z","timestamp":1772428854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of cyclophosphamide for steroid-refractory hepatic acute graft-vs-host disease after allogeneic hematopoietic stem cell 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