{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:20:39Z","timestamp":1778631639361,"version":"3.51.4"},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2018,3,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Endothelial vulnerability is a potential risk factor for complications after allogeneic stem-cell transplantation (alloSCT). The CD40\/CD40 ligand (CD40L) axis contributes to inflammatory diseases and is upregulated in endothelial cells upon activation, suggesting a role in alloSCT biology. Here, we studied single nucleotide polymorphisms (SNPs) in the CD40L gene in recipients of alloSCT. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Three CD40L SNPs (rs3092920, rs3092952, rs3092936) were analyzed for association with transplant-associated thrombotic microangiopathy, overall nonrelapse mortality (NRM), and NRM after acute graft-versus-host disease in 294 recipients of alloSCT without statin-based endothelial prophylaxis (SEP). The significant genotype was then put into perspective with established thrombomodulin ( THBD) gene polymorphisms. Findings were validated in an independent cohort without SEP and in an additional 344 patients who received SEP. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The rs3092936 CC\/CT genotype was associated with an increased risk of transplant-associated thrombotic microangiopathy ( P = .001), overall NRM ( P = .03), and NRM after acute graft-versus-host disease ( P = .01). The rs3092936 CC\/CT genotype was largely mutually exclusive of high-risk THBD SNPs. Both CD40L and THBD SNPs predicted adverse overall survival (OS) and overall NRM to a similar extent in training cohort (OS, P = .04; NRM, P &lt; .001) and validation cohort (OS, P = .01; NRM, P = .001) without SEP. In contrast, SEP completely abolished the influence of the high-risk CD40L and THBD SNPs ( P = .40). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> An increased risk of endothelial complications can be predicted before alloSCT by genetic markers in the recipient\u2019s genome. The normalization of mortality risks in patients treated with SEP suggests a way of overcoming the negative effect of high-risk genotypes and warrants further clinical validation. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2017.76.4662","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T20:59:35Z","timestamp":1516913975000},"page":"789-800","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":16,"title":["Single Nucleotide Polymorphisms in CD40L Predict Endothelial Complications and Mortality After Allogeneic Stem-Cell Transplantation"],"prefix":"10.1200","volume":"36","author":[{"given":"Sivaramakrishna P.","family":"Rachakonda","sequence":"first","affiliation":[{"name":"Sivaramakrishna P. Rachakonda, Hao Dai, and Rajiv Kumar, German Cancer Research Centre; Sivaramakrishna P. Rachakonda, Aleksandar Radujkovic, Carsten M\u00fcller-Tidow, Peter Dreger, and Thomas Luft, University Hospital Heidelberg, Heidelberg; and Olaf Penack, Olga Blau, and Igor Wolfgang Blau, Charit\u00e9 University Medicine Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Dai","sequence":"additional","affiliation":[{"name":"Sivaramakrishna P. Rachakonda, Hao Dai, and Rajiv Kumar, German Cancer Research Centre; Sivaramakrishna P. Rachakonda, Aleksandar Radujkovic, Carsten M\u00fcller-Tidow, Peter Dreger, and Thomas Luft, University Hospital Heidelberg, Heidelberg; and Olaf Penack, Olga Blau, and Igor Wolfgang Blau, Charit\u00e9 University Medicine Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Penack","sequence":"additional","affiliation":[{"name":"Sivaramakrishna P. Rachakonda, Hao Dai, and Rajiv Kumar, German Cancer Research Centre; Sivaramakrishna P. Rachakonda, Aleksandar Radujkovic, Carsten M\u00fcller-Tidow, Peter Dreger, and Thomas Luft, University Hospital Heidelberg, Heidelberg; and Olaf Penack, Olga Blau, and Igor Wolfgang Blau, Charit\u00e9 University Medicine Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Blau","sequence":"additional","affiliation":[{"name":"Sivaramakrishna P. Rachakonda, Hao Dai, and Rajiv Kumar, German Cancer Research Centre; Sivaramakrishna P. Rachakonda, Aleksandar Radujkovic, Carsten M\u00fcller-Tidow, Peter Dreger, and Thomas Luft, University Hospital Heidelberg, Heidelberg; and Olaf Penack, Olga Blau, and Igor Wolfgang Blau, Charit\u00e9 University Medicine Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor Wolfgang","family":"Blau","sequence":"additional","affiliation":[{"name":"Sivaramakrishna P. Rachakonda, Hao Dai, and Rajiv Kumar, German Cancer Research Centre; Sivaramakrishna P. Rachakonda, Aleksandar Radujkovic, Carsten M\u00fcller-Tidow, Peter Dreger, and Thomas Luft, University Hospital Heidelberg, Heidelberg; and Olaf Penack, Olga Blau, and Igor Wolfgang Blau, Charit\u00e9 University Medicine Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar","family":"Radujkovic","sequence":"additional","affiliation":[{"name":"Sivaramakrishna P. Rachakonda, Hao Dai, and Rajiv Kumar, German Cancer Research Centre; Sivaramakrishna P. Rachakonda, Aleksandar Radujkovic, Carsten M\u00fcller-Tidow, Peter Dreger, and Thomas Luft, University Hospital Heidelberg, Heidelberg; and Olaf Penack, Olga Blau, and Igor Wolfgang Blau, Charit\u00e9 University Medicine Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[{"name":"Sivaramakrishna P. 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