IL-7 and SCF Levels Inversely Correlate with T Cell Reconstitution and Clinical Outcomes after Cord Blood Transplantation in Adults.

Abstract

Recovery of thymopoiesis is critical for immune reconstitution after HSCT. IL-7 and SCF are two major thymotropic cytokines. We investigated whether the kinetics of circulating levels of these cytokines might provide insight into the prolonged immunodeficiency after double umbilical cord blood transplantation (dUCBT) in adults. We examined plasma levels of IL-7 and SCF, T-cell receptor rearrangement excision circle (TREC) levels and T cell subsets in 60 adult patients undergoing dUCBT. Median levels of IL-7 increased by more than 3-fold at 4 weeks and remained elevated through 100 days after dUCBT. SCF showed a less than 2-fold increase and more protracted elevation than IL-7. IL-7 levels inversely correlated with the reconstitution of various T cell subsets but not with TRECs. SCF levels inversely correlated with reconstitution of CD4+T cells, especially the naïve CD4+CD45RA+ subset, and with TRECs suggesting that SCF but not IL-7 had an effect on thymic regeneration. In Cox models, elevated levels of IL-7 and SCF were associated with higher non-relapse mortality (p = 0.03 and p = 0.01) and worse overall survival (p = 0.002 and p = 0.001). Elevated IL-7 but not SCF was also associated with development of GvHD (p = 0.03). Thus, IL-7 and SCF are elevated for a prolonged period after dUCBT and persistently high levels of these cytokines may correlate with worse clinical outcomes.