{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T16:18:42Z","timestamp":1755793122379,"version":"3.44.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"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>The introduction of posttransplant cyclophosphamide (PTCy) is one of the major achievements in the field of haploidentical stem cell transplantation (haplo-HCT). The transplant conditioning intensity (TCI) score is a refined classification of conditioning regimens that assigns weight scores to conditioning regimen components. The aim of our analysis was twofold: to assess the effect on transplant outcomes of combining PTCy with calcineurin inhibitor + mycophenolate mofetil (MMF) instead of mTOR inhibitor + MMF for GvHD prophylaxis, and to assess the effect of stratification by conditioning intensity in the setting of haplo-HCT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was conducted in adult patients who underwent haplo-HCT at the University Hospital of Udine (UUH) or Ospedale San Raffaele (OSR) between January 2014 and December 2021. Patients received PTCy plus CsA-MMF at UUH and sirolimus-MMF at OSR. Conditioning intensity was defined by the TCI score. All data were collected prospectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 216 haplo-HCTs were performed, 81 at UUH and 135 at OSR. Notably, none of the patients at UUH received a high TCI score regimen compared to 72 (53.3%) at OSR. Our results show overlapping survival outcomes (OS, NRM, DFS, GRFS, and RI) within the two platforms. We observed a higher incidence of cGvHD within the sirolimus\/MMF + PTCy platform, and high TCI was found to be the only risk factor for a higher incidence of grades III\u2013IV aGvHD in univariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that TCI may reveal the role of chemoradiotherapy in promoting conditions that may contribute to the occurrence of GvHD. The impact of moderate\/severe cGvHD on quality of life must challenge our efforts to further optimise prophylactic strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1610391","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T04:10:20Z","timestamp":1755231020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Post-transplant cyclophosphamide in haploidentical stem cell transplantation: evaluating the impact of transplant conditioning intensity"],"prefix":"10.3389","volume":"16","author":[{"given":"Umberto","family":"Pizzano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Piemontese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Facchin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Greco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta Lisa","family":"Battista","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Peccatori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Fanin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Ciceri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Patriarca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Lupo-Stanghellini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30158-9","article-title":"Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis","volume":"6","author":"Shouval","year":"2019","journal-title":"Lancet Haematol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1182\/blood.2021015129","article-title":"How I prevent GVHD in high-risk patients: posttransplant cyclophosphamide and beyond","volume":"141","author":"Rimando","year":"2023","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2215943","article-title":"Post-transplantation cyclophosphamide - 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