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<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 = 80) or MDS (n = 42) 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–time curve over days 1–30 (AUC30) and 1–100 (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 + 30/+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 ≥ III 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.</p> Graphical abstract <p></p>

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Impact of early tacrolimus exposure on outcomes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Paul Jäger,
  • Andreas Alexander Ralfs,
  • Felicitas Schulz,
  • Nora Liebers,
  • Jonathan Bobak,
  • Ben-Niklas Baermann,
  • Sören Twarock,
  • Alexander Hölscher,
  • Kathrin Nachtkamp,
  • Annika Kasprzak,
  • Joonatan Lavikka,
  • Felix Matkey,
  • Titus Watrin,
  • Malika El Yaouti,
  • Ulrich Germing,
  • Sascha Dietrich,
  • Guido Kobbe

摘要

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 = 80) or MDS (n = 42) 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–time curve over days 1–30 (AUC30) and 1–100 (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 + 30/+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 ≥ III 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.

Graphical abstract