{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:14:49Z","timestamp":1778753689826,"version":"3.51.4"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum D\u00fcsseldorf. Anstalt \u00f6ffentlichen Rechts"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background. Calcineurin inhibitors balance graft-versus-host disease (GvHD) prevention against graft-versus-leukemia (GvL) effects after allogeneic hematopoietic cell transplantation (allo-SCT). Whether the magnitude of early tacrolimus exposure influences relapse or survival remains unclear. Methods. We retrospectively studied 122 adults with AML (n\u2009=\u200980) or MDS (n\u2009=\u200942) undergoing 10\/10 matched-unrelated donor (MUD) allo-SCT from 2014 to 2021. All received rabbit anti-thymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) for GvHD Prophylaxis. Tacrolimus exposure was quantified as area under the concentration\u2013time curve over days 1\u201330 (AUC30) and 1\u2013100 (AUC100). Primary endpoints were overall survival (OS) and event-free survival (EFS); secondary endpoints were cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and GvHD. Analyses included median splits, quartiles\/deciles, competing-risks models, Cox regression, and smoothed 5-year KM estimates across continuous AUC30. Patients with relapse\/death before day\u2009+\u200930\/+100 were excluded from the respective AUC analyses. Results. Median follow-up was 61 months; 5-year OS and EFS were 68% and 43%. Neither AUC30 nor AUC100 (median split or quartiles) was associated with OS, EFS, CIR, or NRM. In multivariable models, tacrolimus exposure was not significant; worse outcomes correlated with older age and female donor for OS, and with AML diagnosis and no CR at allo-SCT for EFS. Smoothed survival across continuous AUC30 showed no meaningful gradient. Any-grade and severe aGvHD, and overall\/grade\u2009\u2265\u2009III chronic GvHD, were comparable across exposure groups. Conclusions. Within a homogeneous MUD\/ATG\/MMF setting, early tacrolimus exposure did not independently predict relapse, NRM, EFS, or OS. Patient and donor factors outweighed tacrolimus AUC. Findings argue against AUC-targeting to improve outcomes; risk-adapted tapering and MRD-guided interventions may offer greater leverage.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-06988-0","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:48:38Z","timestamp":1775713718000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of early tacrolimus exposure on outcomes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes"],"prefix":"10.1007","volume":"105","author":[{"given":"Paul","family":"J\u00e4ger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas Alexander","family":"Ralfs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicitas","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Liebers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Bobak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben-Niklas","family":"Baermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f6ren","family":"Twarock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"H\u00f6lscher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Nachtkamp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Kasprzak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joonatan","family":"Lavikka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Matkey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Titus","family":"Watrin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malika El","family":"Yaouti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Germing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Kobbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"issue":"15","key":"6988_CR1","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1056\/NEJMp078166","volume":"357","author":"FR Appelbaum","year":"2007","unstructured":"Appelbaum FR (2007) Hematopoietic-cell transplantation at 50. 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This study is a retrospective analysis conducted in the public interest using data from patients who had previously provided consent for inclusion in institutional and national registries. No additional, study-specific informed consent was required. The study was approved by the ethics committee of the University Hospital D\u00fcsseldorf (reference 2023\u20132538).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"During the preparation of this manuscript, the authors used AI-assisted tools for language editing and clarity improvement. The authors reviewed and edited the content and take full responsibility for the final manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"232"}}