The Potential Role of Circulating IL-17 Levels During the Peri-Transplant Period as a Predictor for Early Leukemia Relapse After Allogeneic Stem Cell Transplantation.

Abstract 3454

IL-17 is involved in inducing and mediating proinflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become the object of controversy. To determine the role of IL-17 levels during the peri-transplant period on alloreactive responses, serum IL-17 (sIL-17) levels of 95 patients with leukemia (52 AML, 38 ALL, 5 CML) who had undergone myeloablative allogeneic stem cell transplantation were measured using ELISA before conditioning and on day 0, day +7, and day +14 after transplantation. With the median follow-up of 17 months (range, 9–26), overall survival and disease-free survival rates were 70.9%±9.2% and 66.3±6.2%, respectively, and cumulative incidence of relapse and non-relapse mortality were 23.4%±5.7% and 10.3%±3.3%, respectively. Among 18 patients relapsed, 10 patients were relapsed within 180 days (range, 76–172) after transplants, and cumulative incidence of the early relapse was 10.5%±3.2%. The cumulative incidences of acute GVHD with grade II-IV and chronic GVHD were 55.8%±5.1%and 69%±5%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180 days had higher sIL-17 levels during peri-transplant period, whereas no association was detected between sIL-17 levels and other clinical outcomes including acute GVHD. Receiver operating characteristic curve analysis also showed that sIL-17 levels at every time point were available for the prediction of the early relapse. Patients with advanced disease status at transplantation, one of factors associated with early relapse in univariate analyses, had higher sIL-17 levels at pre-conditioning and day 0. However, the result of multivariate analyses showing that sIL-17 levels at each time points were the only factor associated with early relapse suggests the importance of sIL-17 level itself than advanced disease status at transplantation. This study represents the first one demonstrating the early change of sIL-17 during the peri-transplant period and its association with early leukemic relapse in human. The predictive role of sIL-17 during the peri-transplant period for early leukemic relapse may be explained by the association of sIL-17 with tumor itself or tumor growth as well as possible inhibition of the function of graft-versus-leukemia effectors, such as natural killer cell, by sIL-17. Further studies are needed to precisely define the potential roles of IL-17.