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.

Prognostic Impact of Lymphocyte Subpopulations in Peripheral Blood after Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

“…Interestingly, our present study also identified the poor prognostic impact of a high level of na€ ıve thymic T cells at 12 months post-HSCT. Since the increase in na€ ıve thymic T cells may indicate an increase in under-educated T cells with deficient immunity, these results suggest the importance of T cell education as cells with effector immune function in HSCT patients and support previous studies which reported that early thymic reconstitution suggesting sufficient T cell maturation/education, is associated with favorable outcomes after umbilical cord blood transplantation or HSCT (25)(26)(27)(28).…”

Human Herpesvirus-6B Reactivation Is a Risk Factor for Grades II to IV Acute Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

“…After allogeneic HCT, T cell reconstitution is a long process that proceeds along 2 pathways with distinct kinetics: (1) a thymus-independent phase that begins immediately during the early posttransplant period and is mediated by adoptively transferred graft-derived T cells or recipient T cells that survived conditioning and (2) a late thymus-dependent phase that is a prolonged, multistep process that can take up to 18 months after HCT, in which lymphomyeloid progenitor cells repopulate the thymus with thymocyte precursors that can reconstitute thymopoiesis [68,70]. CD4 + lymphopenia, including CD4 + /CD25 + (Treg) lymphopenia, has been associated with high levels of homeostatic cytokines like IL-7, which has been implicated in the pathogenesis of GVHD [71][72][73]. Given that HHV-6 reactivates early and often after HCT and can directly infect and deplete CD4 + cells [17,44,67,68,[74][75][76][77][78][79], it is reasonable to hypothesize that HHV-6 could interfere with early T cell reconstitution [44,67,[74][75][76][77][78][79], resulting in uncontrolled alloreactivity secondary to Treg depletion and leading to aGVHD.…”

Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin

“…19,[22][23][24][25] In contrast to children, however, relatively little is known about immune reconstitution after ATG-free CBT in adults. 12,[26][27][28][29][30] Herein, we report the kinetics of immune reconstitution in a large cohort of adult CBT recipients transplanted for hematologic malignancies at a single center without ATG. We also analyzed the impact of patient, graft, and early posttransplant factors on immune recovery, as well as the immune variables associated with improved survival.…”