Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

SIMPLE SUMMARY: Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for many hematological malignancies and disorders but is often complicated by a relapse of the underlying disease, graft-vs-host disease and infectious complications. However, despite the introduction of calcineurin inhibitors such as tacrolimus, graft-versus-host disease remains one of the major life-threatening complications of allogeneic hematopoietic stem cell transplantation. Due to a variety of factors, there is variability in tacrolimus concentrations during the early weeks post-transplantation. Since the immunologic events leading to acute GVHD also occur in the first few days post-transplantation, it is important that optimal levels be attained early after transplantation. The findings from this study will help inform the management of optimal tacrolimus levels to be attained early post-transplantation. ABSTRACT: Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.