Association of serum interleukin-7 and interleukin-15 levels with immune reconstitution (IR), graft-versus-host disease (GVHD), and survival after reduced-intensity allogeneic stem cell transplantation (RIST)

Abstract

7107 Background: In laboratory models, interleukin-7 (IL-7) and IL-15 significantly influence IR after allogeneic stem cell transplantation (SCT), thereby affecting immunity, graft-versus-malignancy (GVM) effects, and GVHD. Interleukin-7 (IL-7) is the main homeostatic regulator of naïve CD4+ and CD8+ T cells, and IL-15 is homeostatic for CD8+ memory and effector T cells and NK cells. The contributions of these cytokines to IR after allogeneic SCT are not well characterized in a clinical setting. Methods: We studied serum IL-7 and IL-15 levels in 31 pts with hematologic malignancies undergoing RIST from HLA-matched siblings in a prospective trial. Pts received identical transplant conditioning (fludarabine/cyclophosphamide) and GVHD prophylaxis (CSA/MTX). IL-7 and IL-15 levels and peripheral blood lymphocyte subpopulations (ALC, CD3, CD4, CD8, B, NK, and NKT) were measured before RIST, and post RIST at 1 and 2 weeks; 1, 2, 3, 6, 9, and 12 months. Results: Consistent with their homeostatic effects, IL-7 and IL-15 levels rose from baseline as transplant conditioning induced lymphopenia, and then decreased with lymphocyte recovery. These inverse correlations were strongest within 1 month post RIST. In an exploratory analysis, IL-15 levels at day 0 were correlated with baseline age (r=0.49; p=0.0058) and were higher among patients with CMV reactivation after RIST (p=0.048). At 2 weeks post RIST, higher IL-7 levels were strongly associated with subsequent acute GVHD (p=0.000033), and higher IL-15 levels were associated with inferior survival (p=0.007), mainly from relapse. At 3 months post RIST, superior survival was associated with higher NK cell counts (p=0.0008), and to a lesser extent with higher CD4 counts (p=0.036). Conclusions: These data support preclinical observations that IL-7 promotes GVHD after allogeneic SCT. The association of higher post-RIST IL-15 levels with death from relapse may identify pts with impaired IR leading to inadequate GVM effects. This hypothesis is consistent with the finding that higher NK cell counts after RIST were associated with better survival. Further studies must confirm the hypotheses generated in this setting. No significant financial relationships to disclose.