Pre-transplant sTIM-3 levels may have a predictive impact on transplant outcome in acute leukemia patients

Abstract

Objectives: T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is considered as a negative regulator of T-cell driven immune response. This study is planned to investigate the prognostic role of pre-transplant soluble TIM-3 (sTIM-3) levels in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: Pre-transplant serum sTIM-3 levels were measured in 177 allo-HSCT recipients [median age: 36(16–66) years; male/female: 111/66]. Results: Pre-transplant sTIM-3 levels were significantly higher in acute myeloid leukemia (AML) patients compared to acute lymphoblastic leukemia (ALL) patients (p = 0.01). Pre-transplant sTIM-3 levels were significantly lower in patients with abnormal cytogenetics (p = 0.017). Pre-transplant sTIM-3 levels were significantly higher in patients who developed viral hemorrhagic cystitis (p = 0.034). A positive correlation was demonstrated between sTIM-3 levels and acute graft versus host disease (GvHD) grade (p = 0.013; r = 0.299). Overall survival (OS) was not statistically different between low- and high-TIM-3 groups (%35.2 vs %20.4; p > 0.05). Primary diagnosis (p = 0.042), sinusoidal obstruction syndrome (p < 0.001), acute GvHD (p = 0.001), chronic GvHD (p = 0.009) and post-transplant relapse (p = 0.003) represented significant impact on OS. Discussion: Increased sTIM-3 levels in AML patients seem to be compatible with the previous reports. The inhibitor role of TIM-3 in cellular immune response may be a possible explanation for the association of sTIM-3 with viral infections and GvHD. However, the main challenge remains to be the ambiguous association of pre-transplant sTIM-3 levels and post-transplant complications, as allo-HSCT recipients are expected to represent donor genetic features in the post-transplant setting. Conclusion: Further studies are warranted to clarify the particular role of sTIM-3 in the allo-HSCT setting.