{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:03:27Z","timestamp":1781715807699,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>A high CD4\/CD8 T cell ratio in hematopoietic stem cell transplant (HSCT) allografts was observed to predict graft\u2010versus\u2010host disease (GVHD) and nonrelapse mortality (NRM) but has not been comparatively examined in settings of various GVHD\u2010prophylaxis regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective monocentric study included all consecutive HSCT performed with peripheral blood stem cells between January 2000 and June 2021. The impact of the graft CD4\/CD8 ratio was analyzed in three cohorts with different GVHD\u2010prophylaxis platforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the cyclosporine\/mycophenolate\u2010mofetil (CSA\/MMF) cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009294, HLA\u2010matched HSCT), a high (&gt;75th percentile) CD4\/CD8 ratio was associated with increased overall mortality (HR: 1.56;<jats:italic>p<\/jats:italic>\u2009=\u2009.01), increased NRM (HR: 1.85;<jats:italic>p<\/jats:italic>\u2009=\u2009.01) and GVHD\u2010associated mortality (HR: 2.13;<jats:italic>p<\/jats:italic>\u2009=\u2009.005). In the post\u2010transplant cyclophosphamide (PTCy)\/tacrolimus\/MMF cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009113, haploidentical\u2010related or mismatched\u2010unrelated HSCT), a high CD4\/CD8 ratio was associated with increased overall mortality (HR 2.07;<jats:italic>p<\/jats:italic>\u2009=\u2009.04) and aGVHD3\u20104 (HR: 2.24;<jats:italic>p<\/jats:italic>\u2009=\u2009.02). By contrast, in the CSA\/methotrexate (CSA\/MTX) cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009185, HLA\u2010matched HSCT) the CD4\/CD8 ratio had no significant impact on any of the investigated endpoints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A high CD4\/CD8 ratio in the allograft has an adverse impact on GVHD and survival in CSA\/MMF\u2010 and PTCy\u2010based HSCT, while MTX\u2010based prophylaxis may largely alleviate this important risk factor.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.13956","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T04:24:13Z","timestamp":1679372653000},"page":"715-724","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Adverse impact of a high<scp>CD4<\/scp>\/<scp>CD8<\/scp>ratio in the allograft may be overcome by methotrexate\u2010 but not mycophenolate\u2010 or post\u2010transplant cyclophosphamide\u2010based graft versus host disease prophylaxis"],"prefix":"10.1111","volume":"110","author":[{"given":"A.","family":"Nikoloudis","sequence":"first","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-9700","authenticated-orcid":false,"given":"V.","family":"Buxhofer\u2010Ausch","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Aichinger","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Binder","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hasengruber","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kaynak","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Wipplinger","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Milanov","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Strassl","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Stiefel","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Machherndl\u2010Spandl","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Petzer","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Weltermann","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Clausen","sequence":"additional","affiliation":[{"name":"Ordensklinikum Linz\u2014Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation Hemostaseology and Medical Oncology Linz Austria"},{"name":"Johannes Kepler University Medical Faculty Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70225-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2008.03.005"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917635"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2033122"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03360.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2009.10.021"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2008.267"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-009-0728-4"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23107"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.8817"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13537"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.227371"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-02278-5"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.12.012"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.01.010"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.2446"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.03.016"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-552984"},{"issue":"6","key":"e_1_2_10_22_1","first-page":"825","article-title":"1994 consensus conference on acute GVHD grading","volume":"15","author":"Przepiorka D","year":"1995","journal-title":"Bone Marrow Transplant"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(80)90380-0"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2005.09.004"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1279"},{"key":"e_1_2_10_26_1","unstructured":"Team RC.R: A language and environment for statistical computing: R Foundation for Statistical Computing.2022Available from:https:\/\/www.R-project.org\/"},{"key":"e_1_2_10_27_1","unstructured":"TherneauT.A Package for Survival Analysis in S.2022Available from:https:\/\/CRAN.R-project.org\/package=survival"},{"key":"e_1_2_10_28_1","unstructured":"GerdsTA OzenneB.riskRegression: risk regression models and prediction scores for survival analysis with competing risks.2022Available from:https:\/\/CRAN.R-project.org\/package=riskRegression"},{"key":"e_1_2_10_29_1","unstructured":"GrayB.cmprsk: subdistribution analysis of competing risks.2022Available from:https:\/\/CRAN.R-project.org\/package=cmprsk"},{"key":"e_1_2_10_30_1","unstructured":"Cowplot WCO.Streamlined Plot Theme and Plot Annotations for \u2018ggplot2\u2019.2022Available from:https:\/\/CRAN.R-project.org\/package=cowplot"},{"key":"e_1_2_10_31_1","unstructured":"KassambaraA KosinskiM BiecekP.survminer: drawing survival curves using \u2018ggplot2\u2019.2022Available from:https:\/\/CRAN.R-project.org\/package=survminer"},{"key":"e_1_2_10_32_1","unstructured":"HarrisonE DrakeT FinalfitOR.Quickly create elegant regression results tables and plots when Modelling.2022Available from:https:\/\/CRAN.R-project.org\/package=finalfit"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"issue":"2","key":"e_1_2_10_34_1","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines5020013","article-title":"HLA\u2010C KIR\u2010ligands determine the impact of anti\u2010Thymocyte globulin (ATG) on graft versus host and graft versus leukemia effects following hematopoietic stem cell transplantation","volume":"5","author":"Clausen J","year":"2017","journal-title":"Biomedicines"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(01)00737-8"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.60.1203"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2004.07.020"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2004.12.004"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-019-0165-8"},{"issue":"2016","key":"e_1_2_10_40_1","first-page":"5601204","article-title":"Donor cell composition and reactivity predict risk of acute graft\u2010versus\u2010host disease after allogeneic hematopoietic stem cell transplantation","volume":"14","author":"Sairafi D","year":"2016","journal-title":"J Immunol Res"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240801927032"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.13956","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.13956","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T18:40:40Z","timestamp":1729104040000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.13956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,28]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1111\/ejh.13956"],"URL":"https:\/\/doi.org\/10.1111\/ejh.13956","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,28]]},"assertion":[{"value":"2022-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}