Interleukin 12 Is Associated with Reduced Relapse without Increased Incidence of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Interleukin (IL)-12 has antitumor effects in murine studies. To evaluate this clinically, we investigated whether high levels of circulating IL-12 in patients after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with improved relapse-free survival. We prospectively studied 134 patients undergoing HSCT. Median follow-up was 1158 days (range, 70-1792 days). Plasma IL-12 levels were measured before transplantation and on days 0, +4, +7, and +14 after transplantation. The highest levels were seen on days +4 and +7 and were categorized by a cluster analysis of the logarithmically transformed IL-12 concentrations, which were then correlated with relapse-free survival. Forty-six patients had low levels of IL-12 (median, 2 pg/mL; range, 0-6.5 pg/mL), 49 patients had medium levels (median, 20.5 pg/mL; range, 7-75.5 pg/mL), and 25 patients had high levels (median, 181 pg/mL; range, 84-623 pg/mL). Patients with high IL-12 levels before transplantation had the highest increase after transplantation. With a multivariate Cox model for relapse onset, with the low IL-12 level as the reference, patients in the high-IL-12 group had an adjusted hazard ratio of 0.27 (95% confidence interval, 0.09-0.79), and medium group patients had a hazard ratio of 0.65 (95% confidence interval, 0.31-1.36). The incidences of relapse at 500 days by Kaplan-Meier analysis by IL-12 group were 23.0% (high group), 40.3% (medium group), and 48.8% (low group). There was no association between IL-12 levels and the risk of acute graft-versus-host disease (GVHD; P = .51) or chronic GVHD (P = .28). In conclusion, high IL-12 levels after HSCT are associated with improved relapse-free survival without increasing the risk for GVHD. Patients with high pretransplantation IL-12 levels have an increased likelihood of higher posttransplantation IL-12 levels, possibly because of a host-graft interaction, and this may predispose to better clinical outcomes.