Polymorphisms of NOD2/CARD15 Are Associated with Clinical Outcome in T-Cell Depleted HLA-Identical Sibling Allogeneic Stem Cell Transplantation.

Three single nucleotide polymorphisms (SNP) in NOD2/CARD15 have been associated with the incidence and severity of acute GVHD following allogeneic stem cell transplantation (allo-SCT). The potential clinical influence of SNP in NOD2/CARD15 in a model of allo-SCT with a low incidence of GVHD, such as T-cell depleted transplants (TCD), has not been studied. We analyzed the association of SNP in NOD2/CARD15 with the outcome of 84 patients undergoing allo-SCT with TCD by means of CD34+ selection. Results were compared with a concurrent group of 94 patients receiving an allo-SCT with unmanipulated grafts (Non-TCD). Transplants were performed in a single institution, donors were HLA identical siblings and all patients received myeloablative-conditioning regimen. Median follow-up was of 30.6 months (range, 0.2–112). SNP 8, 12 and 13 were analyzed by RT-PCR allelic discrimination method in all patients and in 137 donors. SNP in NOD2/CARD15 were detected in 13.8% of patients and in 10.7% of donors. Results of the association of patient’s NOD2/CARD15 genotype and outcome are given in the table. In TCD transplants, independent risk factors associated with event free survival in a multivariate analysis were: patient’s NOD2/CARD15 genotype (RR 2.7, p=0.02), patient’s age (RR 2.3, p=0.03) and conditioning with radiotherapy (RR 2.7, p=0.03). The only association of donor’s NOD2/CARD15 genotype with clinical outcome in the multivariate analysis was with acute GVHD (RR 3.3, p=0.03). In conclusion, polymorphisms in NOD2/CARD15 have a strong association with clinical outcome in TCD transplants, which is independent of GVHD.