title: Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination.
abstract: To assess the role of NOD2/CARD15 variants on the long-term outcome of allogeneic stem cell transplantation in a genetically homogeneous group, we extended our previous study (cohort I, n = 78) and typed DNA for NOD2/CARD15 single nucleotide polymorphisms (SNPs) from an additional 225 recipients and their HLA-identical sibling donors (cohort II) treated at four other European centers. Results of genotyping were compared with clinical outcome. The strong association of NOD2/CARD15 variants with transplantation-related mortality (TRM) was confirmed in univariate and multivariate analysis; TRM increased from 20% in cohort I/22% in cohort II in recipient/donor pairs without any NOD2/CARD15 variants to 47% in cohort I/32% in cohort II in the presence of one variant in either donor or recipient and further to 57% in cohort I/74% in cohort II in the presence of 2 or more variants (P < .002 in both cohorts). NOD2/CARD15 SNPs were not associated with relapse rate but had a strong impact on overall survival. In an analysis of center effects, the type of gastrointestinal decontamination was the only factor interfering with the prognostic significance of NOD2/CARD15 SNPs. Our data further support an interaction between gastrointestinal defense mechanisms, activation of the innate immune system, and specific transplant-related complications.
authors.affiliation: Department of Haematology/Oncology, Medical Centre, University of Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany. ernst.holler@klinik.uni-regensburg.de
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: Joachim
authors.initials: J
authors.lastname: Hahn
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Gottfried
authors.initials: G
authors.lastname: Fischer
authors.forename: Graham
authors.initials: G
authors.lastname: Jackson
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
authors.forename: Beate
authors.initials: B
authors.lastname: Steiner
authors.forename: Guenther
authors.initials: G
authors.lastname: Eissner
authors.forename: Jeorg
authors.initials: J
authors.lastname: Marienhagen
authors.forename: Juergen
authors.initials: J
authors.lastname: Schoelmerich
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics*; D006402:Hematologic Diseases / Q000235:genetics / Q000628:therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein