G to C transition at position −173 of MIF gene of the recipient is associated with reduced relapse rates after allogeneic stem cell transplantation

Abstract

Pro-inflammatory and dendritic cell-activating properties of macrophage migration inhibitory factor (MIF) suggest a potentially important role for MIF in alloantigen-specific immune responses after allogeneic stem cell transplantation (allo-SCT). We tested whether MIF −173 G/C gene polymorphism of donor or patient had impacts on the outcomes after allo-SCT. Four hundred and fifty-four donor–patient pairs were genotyped and mortality, relapse, and development of complications were analyzed. Patient but not donor MIF −173∗C allele was associated with improved overall survival (OS) (5 years: 60.8% versus 46.3%, p = 0.042) and disease free survival (DFS) (5 years: 55.4% versus 39.5%; p = 0.014) due to a reduction in relapse (day 2000: 22.8% versus 42.0% p = 0.006) but not due to decreased transplantation-related mortality (TRM) ( p = 0.44). Multivariate analysis proved patient −173∗C allele as an independent factor for reducing relapse after allo-SCT ( p = 0.023). Subgroup analysis showed a clear MIF −173∗C allele-related reduction in relapse for those patients who did not receive T cell depleted (TCD) SCT ( p = 0.01) in contrast to patients receiving TCD SCT ( p = 0.20). In summary, patient MIF −173∗C allele may be linked to specific, yet unrevealed functions in tumor biology and graft versus leukemia and lymphoma effects and potentially presents a novel prognostic marker for patient-tailored counseling and therapy in allo-SCT.