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.