{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:35:32Z","timestamp":1791858932071,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Complement activation has shown a role in murine models of graft\u2010versus\u2010host disease (GVHD) and in endothelial complications after allogeneic hematopoietic cell transplantation (allo\u2010HSCT). However, its impact on post\u2010transplant outcomes has not been so far fully elucidated. Here, we conducted a prospective multicentric trial (NCT01520623) performing serial measurements of complement proteins, regulators, and CH50 activity for 12\u2009weeks after allo\u2010HSCT in 85 patients receiving a myeloablative conditioning (MAC) regimen for various hematological malignancies. Twenty\u2010six out of 85 patients showed an \u201cactivated\u201d complement profile through the classical\/lectin pathway, defined as a post\u2010transplant decline of C3\/C4 and CH50 activity. Time\u2010dependent Cox regression models demonstrated that complement activation within the first weeks after allo\u2010HSCT was associated with increased non\u2010relapse mortality (hazard ratio [HR]: 3.69, 95% confident interval [CI]: 1.55\u20138.78, <jats:italic>p<\/jats:italic>\u2009=\u2009.003) and poorer overall survival (HR: 2.72, 95% CI: 1.37\u20135.39, <jats:italic>p<\/jats:italic>\u2009=\u2009.004) due to increased incidence of grade II\u2013IV acute GVHD and in particular gastrointestinal (GI) GVHD (HR: 36.8, 95% CI: 12.4\u2013109.1, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), higher incidences of thrombotic microangiopathy (HR: 8.58, 95% CI: 2.16\u201334.08, <jats:italic>p<\/jats:italic>\u2009=\u2009.0022), capillary leak syndrome (HR: 7.36, 95% CI: 2.51\u201321.66, <jats:italic>p<\/jats:italic>\u2009=\u2009.00028), post\u2010engraftment bacterial infections (HR: 2.37, 95% CI: 1.22\u20134.63, <jats:italic>p<\/jats:italic>\u2009=\u2009.0108), and EBV reactivation (HR: 3.33, 95% CI: 1.31\u20138.45, <jats:italic>p<\/jats:italic>\u2009=\u2009.0112). Through specific immune staining, we showed the correlation of deposition of C1q, C3d, C4d, and of C5b9 components on endothelial cells in GI GVHD lesions with the histological grade of GVHD. Altogether these findings define the epidemiology and the clinical impact of complement classical\/lectin pathway activation after MAC regimens and provide a rational for the use of complement inhibitory therapeutics in a post\u2010allo\u2010HSCT setting.<\/jats:p>","DOI":"10.1002\/ajh.27030","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T14:49:44Z","timestamp":1690037384000},"page":"1559-1570","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Systemic complement activation influences outcomes after allogeneic hematopoietic cell transplantation: A prospective <scp>French<\/scp> multicenter trial"],"prefix":"10.1002","volume":"98","author":[{"given":"Anne B\u00e9atrice","family":"Notarantonio","sequence":"first","affiliation":[{"name":"Service d'H\u00e9matologie, H\u00f4pital Brabois, CHRU Nancy and CNRS UMR 7365, IMoPA Biop\u00f4le de l'Universit\u00e9 de Lorraine  Vandoeuvre\u2010les\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-2742","authenticated-orcid":false,"given":"Maud","family":"D'aveni\u2010Piney","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie, H\u00f4pital Brabois, CHRU Nancy and CNRS UMR 7365, IMoPA Biop\u00f4le de l'Universit\u00e9 de Lorraine  Vandoeuvre\u2010les\u2010Nancy France"},{"name":"Laboratory of Physiopathology of Hematological Disorders and Their Therapeutic Implications, INSERM U1158 Imagine Institute Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Pagliuca","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie, H\u00f4pital Brabois, CHRU Nancy and CNRS UMR 7365, IMoPA Biop\u00f4le de l'Universit\u00e9 de Lorraine  Vandoeuvre\u2010les\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayha","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Laboratoire d'Immunologie, H\u00f4pital Europ\u00e9en Georges\u2010Pompidou, Universit\u00e9 Paris Cit\u00e9 and UMR S 1138 Centre de Recherche des Cordeliers  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques\u2010Emanuel","family":"Galimard","sequence":"additional","affiliation":[{"name":"EBMT Paris Study Office CEREST\u2010TC  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali\u00e9nor","family":"Xhaard","sequence":"additional","affiliation":[{"name":"BMT Unit, Saint\u2010Louis Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) University of Paris VII  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambroise","family":"Mar\u00e7ais","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Clinique, Assistance Publique\u2010H\u00f4pitaux de Paris H\u00f4pital Necker  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Suarez","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Clinique, Assistance Publique\u2010H\u00f4pitaux de Paris H\u00f4pital Necker  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eolia","family":"Brissot","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Clinique et de Th\u00e9rapie Cellulaire, Assistance Publique\u2010H\u00f4pitaux de Paris H\u00f4pital Saint\u2010Antoine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Feugier","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie, H\u00f4pital Brabois, CHRU Nancy and CNRS UMR 7365, IMoPA Biop\u00f4le de l'Universit\u00e9 de Lorraine  Vandoeuvre\u2010les\u2010Nancy 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