title: 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.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg Medical Center, Regensburg, Germany.
authors.forename: Ya-Yi
authors.initials: YY
authors.lastname: Chang
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Gerhard C
authors.initials: GC
authors.lastname: Hildebrandt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012008:Recurrence; D033581:Stem Cell Transplantation; D055815:Young Adult
chemical_list: D008263:Macrophage Migration-Inhibitory Factors