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

• Published in: Blood 2006-05, Vol.107 (10), p.4189-4193
• Main Authors: Holler, Ernst, Rogler, Gerhard, Brenmoehl, Julia, Hahn, Joachim, Herfarth, Hans, Greinix, Hildegard, Dickinson, Anne M., Socié, Gerard, Wolff, Daniel, Fischer, Gottfried, Jackson, Graham, Rocha, Vanderson, Steiner, Beate, Eissner, Guenther, Marienhagen, Jeorg, Schoelmerich, Juergen, Andreesen, Reinhard
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Child; Child, Preschool; Cohort Studies; Female; Genetic Variation; Hematologic Diseases - genetics; Hematologic Diseases - therapy; HLA Antigens - genetics; Humans; Intracellular Signaling Peptides and Proteins - genetics; Leukemia - genetics; Leukemia - therapy; Male; Medical sciences; Middle Aged; Nod2 Signaling Adaptor Protein; Polymorphism, Single Nucleotide; Siblings; Stem Cell Transplantation; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Homologous; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-09-3741

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.