Impact of early tacrolimus levels on survival outcomes following allogeneic hematopoietic stem cell transplantation.

Abstract

e18563 Background: Tacrolimus is routinely used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (HSCT); however, the prognostic impact of early post-transplant tacrolimus exposure remains unclear. We evaluated the association between tacrolimus levels within 30 days after allogeneic HSCT and survival outcomes. Methods: This is a single-center retrospective study of 72 adult patients who underwent matched related (MR), matched unrelated (MU), or haploidentical allogeneic HSCT between January 2024 and May 2025. For each patient, measurements of tacrolimus exposure within 30 days post-transplant (mean, standard error of the mean [SEM], variance, minimum, maximum, and number of levels <7 ng/mL) were calculated and analyzed for associations with clinical and survival outcomes. Results: The median age was 60 years; 45.8% were male, and 80.6% were White. Donor types included MU (63.9%), MR (6.9%), and haploidentical donors (29.2%). Myeloablative and reduced-intensity conditioning were used in 68.1% and 31.9% of patients, respectively. The mean tacrolimus level was 8.45 ng/mL (SEM 0.19), with a variance of 2.74 and a range of 5.5–13.9 ng/mL. The median number of tacrolimus levels <7 ng/mL was six. Median follow-up was 14 months, and the estimated 1-year overall survival (OS) was 90.1%. On univariate analysis, higher mean tacrolimus levels were associated with inferior OS (OR 1.49, 95% CI 1.00–2.23, p=0.048), but not with acute kidney injury (p=0.30), acute (p=0.39) or chronic GVHD (p=0.21), relapse (p=0.93), 100-day (p=0.10) or 1-year survival (p=0.35), or non-relapse mortality (NRM, p=0.07). Higher SEM was associated with increased NRM (OR 2.68, 95% CI 1.11–6.46, p=0.028) and worse OS (OR 2.36, 95% CI 1.02–5.44, p=0.044). Other tacrolimus metrics, including variance, minimum, or maximum of tacrolimus level and numbers of tacrolimus level <7 ng/ml, were not significantly associated with NRM (p=0.06, p=0.86, p=0.06, p=0.72) or OS (p=0.08, p=0.68, p=0.10, p=0.63), respectively. On multivariate Cox proportional hazards analysis, higher mean tacrolimus level remained independently associated with inferior OS (HR 8.56, 95% CI 1.38–53.13, p=0.02), whereas SEM was not (HR 0.20, 95% CI 0.02–1.70, p=0.14). In a second multivariate model, a mean tacrolimus level >11 ng/mL was significantly associated with worse OS (HR 13.69, 95% CI 1.35–139.03, p=0.03), independent of age, donor type, number of antigen mismatches, conditioning intensity, HCT-CI score, incidence of acute or chronic GVHD, and infection. Conclusions: Higher early tacrolimus exposure, particularly mean levels >11 ng/mL, was independently associated with inferior OS after allogeneic HSCT. Other measures of tacrolimus variability were not significantly associated with survival. Future studies are warranted to clarify the mechanisms underlying these findings.