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

Lookup NU author(s): Professor Anne Dickinson, Professor Graham Jackson

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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). Muitivariate analysis proved patient - 173*C allele as an indepepdent 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. (C) 2009 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Chang YY, Greinix HT, Dickinson AM, Wolff D, Jackson GH, Andreesen R, Holler E, Hildebrandt GC

Publication type: Article

Publication status: Published

Journal: Cytokine

Year: 2009

Volume: 48

Issue: 3

Pages: 218-225

ISSN (print): 1043-4666

ISSN (electronic): 1096-0023

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.cyto.2009.07.012

DOI: 10.1016/j.cyto.2009.07.012


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Funding

Funder referenceFunder name
European Community
LSHB-CT-2007-037703STEMDIAGNOSTICS
MRTN-CT-2004-512253TRANS-NET
QLRT-CT-2001-01936TRANSEUROPE

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