Increase of interleukin-18 serum levels after engraftment correlates with acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation.

Abstract

Acute graft-versus-host disease (GvHD) is a constant and severe complication after allogeneic stem cell transplantation regularly involving skin, liver, gut, and lungs. The cytokine interleukin-18 (IL-18) has been shown to increase in patients who develop acute GvHD after bone marrow tranplantation (BMT). Here, we measured IL-18 serum levels after peripheral blood stem cell transplantation (PBSCT) at several characteristic time points in 24 patients (median age 46 years). Patients received a median of 7.3 x 10(6)/kg bodyweight CD34-positive blood stem cells from HLA-matched family donors (n = 5), matched unrelated donors (n = 18), and one mismatched unrelated donor. GvHD prophylaxis consisted of cyclosporin A alone or combined with methotrexate and/or mycophenolate mofetil. In 14 patients we observed no GvHD or only GvHD grade I whereas ten patients developed GvHD grade II-IV post transplant. Low, intermediate, and high levels of serum IL-18 were found in patients after allogeneic PBSCT independently of GvHD after transplantation. In contrast to GvHD arising after BMT, there was no clear correlation between absolute IL-18 serum levels and GvHD grade after PBSCT. However, the individual time course of IL-18 serum level after engraftment correlates with acute GvHD after PBSCT. In detail, an increase of serum IL-18 of at least 1.6-fold after engraftment is associated with acute GvHD II or higher with a sensitivity of three out of four. Using the 1.6 "cut-off" for IL-18 increase after engraftment, a specificity of up to 100% can be achieved. The time course of IL-18 serum levels might be used for GvHD prediction after PBSCT comparable to absolute serum levels after BMT.