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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

Lookup NU author(s): Professor Anne Dickinson


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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.

Publication metadata

Author(s): Holler E, Rogler G, Brenmoehl J, Hahn J, Herfarth H, Greinix H, Dickinson AM, Socie G, Wolff D, Fischer G, Jackson G, Rocha V, Steiner B, Eissner G, Marienhagen J, Schoelmerich J, Andreesen R

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2006

Volume: 107

Issue: 10

Pages: 4189-4193

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2005-09-3741


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