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.
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.
Holler
Ernst
E
Department of Haematology/Oncology, Medical Centre, University of Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany. ernst.holler@klinik.uni-regensburg.de
Rogler
Gerhard
G
Brenmoehl
Julia
J
Hahn
Joachim
J
Herfarth
Hans
H
Greinix
Hildegard
H
Dickinson
Anne M
AM
Socié
Gerard
G
Wolff
Daniel
D
Fischer
Gottfried
G
Jackson
Graham
G
Rocha
Vanderson
V
Steiner
Beate
B
Eissner
Guenther
G
Marienhagen
Jeorg
J
Schoelmerich
Juergen
J
Andreesen
Reinhard
R
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
D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein