{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:12:02Z","timestamp":1776949922839,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["2008\u20104331"],"award-info":[{"award-number":["2008\u20104331"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["2009\u20104590"],"award-info":[{"award-number":["2009\u20104590"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cyclosporine A combined with mycophenolate mofetil (CsA\/MMF) has become an established regimen for the prevention of graft\u2010versus\u2010host disease (GVHD) following non\u2010myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time\u2010restricted IS with CsA\/MMF would increase the proportion of patients with non\u2010severe GVHD compared to standard\u2010duration IS, thereby resulting in reduction of the relapse rate and improvement of progression\u2010free survival (PFS) and overall survival (OS). In a prospective randomized, multicenter, phase III trial, patients were allocated (1:1) to standard or time\u2010restricted IS. A total of 389 patients were randomized, of whom 369 were transplanted (184 vs. 185 patients). The primary endpoint, the proportion of patients with non\u2010severe GVHD defined as acute GVHD grades I\u2013II without gut involvement or chronic GVHD not requiring systemic treatment within 180 days posttransplant, was 23% after standard\u2010duration IS versus 24% after time\u2010restricted IS (odds ratio: 1.02; 95% confidence interval (CI) 0.63\u20131.66, <jats:italic>p<\/jats:italic>\u2009=\u20090.92). The cumulative incidence of grade III\u2013IV acute GVHD at 6 months posttransplant was not significantly different (14% vs. 18%; <jats:italic>p<\/jats:italic>\u2009=\u20090.20). The two\u2010year cumulative incidence of chronic extensive GVHD was 50% versus 46% (<jats:italic>p<\/jats:italic>\u2009=\u20090.62). There were no significant differences in the rates of relapse\/progression, non\u2010relapse mortality, PFS, OS, and GVHD\u2010free, relapse\u2010free survival. Time\u2010restricted IS with CsA\/MMF did not increase the proportion of patients with non\u2010severe GVHD, and secondary outcomes were not different compared to standard\u2010duration IS following NMA\u2010matched alloHSCT.<\/jats:p>","DOI":"10.1002\/hem3.70040","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T11:14:58Z","timestamp":1733915698000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Time\u2010restricted versus standard\u2010duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON\u201096 trial"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-0966","authenticated-orcid":false,"given":"Annoek E. C.","family":"Broers","sequence":"first","affiliation":[{"name":"Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC location VU Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-2671","authenticated-orcid":false,"given":"Bronno","family":"van der Holt","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands"},{"name":"HOVON Foundation Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis N.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Gelderse Vallei Hospital Ede The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erfan","family":"Nur","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geerte L.","family":"van Sluis","sequence":"additional","affiliation":[{"name":"Department of Hematology Isala Klinieken Zwolle The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goda","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Hematology, UMC Groningen University of Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"van Gelder","sequence":"additional","affiliation":[{"name":"Department of Hematology Maastricht UMC+ Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan A.","family":"Maertens","sequence":"additional","affiliation":[{"name":"Department of Hematology University Hospitals Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Kuball","sequence":"additional","affiliation":[{"name":"Department of Hematology UMC Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dries","family":"Deeren","sequence":"additional","affiliation":[{"name":"Department of Hematology AZ Delta Roeselare Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heleen A.","family":"Visser\u2010Wisselaar","sequence":"additional","affiliation":[{"name":"HOVON Foundation Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamberdina A. H. M.","family":"Meulendijks","sequence":"additional","affiliation":[{"name":"HOVON Foundation Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan J.","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the HOVON Stem Cell Transplantation Working Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.3.756"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"18","article-title":"Harnessing graft\u2010versus\u2010malignancy: non\u2010myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy","volume":"111","author":"Champlin R","year":"2008","journal-title":"Br J Haematol"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.11.3390"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-05-1340"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01771"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000203556.06145.5b"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2013.204"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3868"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-6143.2003.00337.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000209411.66790.b3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.5.6.1333"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005847"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1037\/1040-3590.14.4.439"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1700672"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-609032"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-197410000-00001"},{"issue":"6","key":"e_1_2_10_18_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_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.2003.50026"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23882"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.362"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.45"},{"issue":"4","key":"e_1_2_10_23_1","first-page":"194","article-title":"Methotrexate and cyclosporine for graft\u2010vs.\u2010host disease prevention: what length of therapy with cyclosporine","volume":"3","author":"Storb R","year":"1997","journal-title":"Biol Blood Marrow Transplant"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-330217"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-302109"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03643"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70225-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506002"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00462-3"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30256-X"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30088-2"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2020.10.016"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2008.03.005"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02293"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2215943"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.07.005"}],"container-title":["HemaSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T10:56:11Z","timestamp":1760352971000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hem3.70040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":35,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/hem3.70040"],"URL":"https:\/\/doi.org\/10.1002\/hem3.70040","archive":["Portico"],"relation":{},"ISSN":["2572-9241","2572-9241"],"issn-type":[{"value":"2572-9241","type":"print"},{"value":"2572-9241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2023-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70040"}}