The impact of tacrolimus levels on acute GVHD and transplant outcomes in haploidentical hematopoietic stem cell transplantation: A retrospective analysis

• Published in: Cell transplantation Vol. 34; p. 9636897251366368
• Main Authors: Nikoloudis, Alexander, Buxhofer-Ausch, Veronika, Kunte, Ameya, Groiss, Christina, Mair, Lorenz, Aichinger, Christoph, Binder, Michaela, Hasengruber, Petra, Kaynak, Emine, Wipplinger, Dagmar, Milanov, Robert, Strassl, Irene, Stiefel, Olga, Machherndl-Spandl, Sigrid, Rumpold, Holger, Weltermann, Ansgar, Petzer, Andreas, Clausen, Johannes
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.08.2025; Sage Publications Ltd; SAGE Publishing
• Subjects: Adolescent; Adult; Blood levels; Cyclophosphamide; Female; Graft vs Host Disease - blood; Graft vs Host Disease - drug therapy; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Immunosuppressive Agents - therapeutic use; Lymphocytes T; Male; Middle Aged; Multivariate analysis; Mycophenolic acid; Original; Retrospective Studies; Stem cell transplantation; Tacrolimus; Tacrolimus - blood; Tacrolimus - therapeutic use; Transplantation, Haploidentical - methods; Treatment Outcome; Young Adult; tacrolimus; haploidentical transplantation with posttransplant cyclophosphamide and tacrolimus mycophenolate mofetil; acute graft-versus-host-disease
• ISSN: 0963-6897; 1555-3892; 1555-3892
• DOI: 10.1177/09636897251366368

The impact of early tacrolimus (TAC) blood levels on acute graft-versus-host disease (aGVHD) and transplant outcomes in adults undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with posttransplant cyclophosphamide (PTCy) is incompletely investigated. We retrospectively analyzed 161 T-cell–replete haplo-HSCT with PTCy, TAC, and mycophenolate-mofetil. TAC trough levels from weeks 1–2 (w1/2) and weeks 3–4 (w3/4) posttransplant were categorized as “Low” or “High” using a threshold of 10 ng/ml. Outcomes assessed included grade III–IV acute graft-versus-host-disease (aGVHD), nonrelapse mortality (NRM), relapse, and overall survival (OS). Multivariate analyses controlled for relevant patient and transplant factors. Higher w1/2 TAC (≥10 ng/ml) in weeks 1–2 had no association with aGVHD III/IV (35% vs. 35%, P = 0.71). Higher TAC levels during w3/4 were associated with a trend toward decreased aGVHD III–IV incidence (8% vs. 20%; P = 0.09). Multivariate analysis confirmed w3/4 TAC levels as protective against aGVHD III/IV (sub-Hazard Ratio [sHR] = 0.83, 95% CI: 0.70–0.98, P = 0.03) and NRM (sHR = 0.82, 95% CI: 0.71–0.95, P = 0.01), while w1/2 TAC levels had no significant impact on the above outcomes. TAC levels did not significantly impact OS or relapse. We conclude that following PTCy-based haplo-HSCT, higher TAC levels during weeks 3–4 may decrease aGVHD and NRM. Graphical Abstract