Area under tacrolimus concentrations predict outcomes after unrelated allogeneic hematopoietic stem cell transplantation.

Previous studies have shown that the blood concentration of calcineurin inhibitors is related to the incidence of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its utility as an indicator for GVHD relapse prevention and graft-versus-tumor effect assessment has mostly been investigated in umbilical cord blood transplantation. We hypothesized that the simple area under the tacrolimus (TAC) concentration (AUTC) early after transplantation reflects TAC pharmacokinetics more accurately than the mean TAC concentration (MTC), and analyzed the relationship of AUTC with outcomes after unrelated allo-HSCT for myeloid malignancies. We set cut-off values of MTCs and AUTCs using receiver-operating-characteristic curves for each outcome. Patients with high MTC in week 3 (MTC 3) had a lower cumulative incidence of acute GVHD. High MTC 3 was associated with a higher relapse rate in univariate analysis, but was not significant in multivariate analysis. Meanwhile, high AUTC in week 3 (AUTC 3) was a predictor of relapse, worse relapse-free survival, and overall survival in both univariate and multivariate analysis. Development of acute GVHD was not associated with relapse. Therefore, AUTC 3 after unrelated allo-HSCT for myeloid malignancies may better reflect the relapse prevention effect of immunosuppression intensity than MTC or development of acute GVHD.