title: NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation.
abstract: Single nucleotide polymorphisms (SNPs) in the NOD2 gene have significant impact on both treatment-related mortality (TRM) and acute GVHD (aGVHD) in haematopoietic stem cell transplantation (HSCT). The effect of these polymorphisms when using T-cell-depleted grafts has been poorly studied. We retrospectively analysed NOD2 polymorphisms in a cohort of 85 patients and donors who received an HLA-identical sibling partially T-cell-depleted HSCT (0.5 x 10(6) CD3+ T cells per kg) following idarubicin-containing conditioning regimens. NOD2 polymorphisms were present in 14 of 85 (16.5%) of patients and 18 of 85 (21%) of donors. The risk of severe aGVHD (grade III-IV) and the 1-year TRM was significantly higher in the presence of NOD2 polymorphisms (hazard ratio (HR) 6.0, P=0.02 for severe aGVHD and HR 3.3, P=0.02 for TRM, respectively) and was most prominent in cases where patient and donor both had a polymorphism (HR 10.5, P=0.002 and HR 3.9, P=0.002). There was also a trend towards increased risk of bacteraemia due to coagulase-negative staphylococci in patients with an NOD2 polymorphism. We conclude that NOD2 polymorphism screening should be used to optimize donor selection and antimicrobial prophylaxis to reduce the occurrence of aGVHD and TRM following allogeneic HSCT.
authors.affiliation: Department of Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. w.vandervelden@hemat.umcn.nl
authors.forename: W J F M
authors.initials: WJ
authors.lastname: van der Velden
authors.forename: N M A
authors.initials: NM
authors.lastname: Blijlevens
authors.forename: F M H M
authors.initials: FM
authors.lastname: Maas
authors.forename: N P M
authors.initials: NP
authors.lastname: Schaap
authors.forename: J H
authors.initials: JH
authors.lastname: Jansen
authors.forename: B A
authors.initials: BA
authors.lastname: van der Reijden
authors.forename: T
authors.initials: T
authors.lastname: Feuth
authors.forename: H
authors.initials: H
authors.lastname: Dolstra
authors.forename: J P
authors.initials: JP
authors.lastname: Donnelly
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005787:Gene Frequency; D014644:Genetic Variation; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007113:Immunity, Innate; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014019:Tissue Donors; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein