Abstract
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.Overall group (n=178) SNP vs. WTP*TCD (n=84) SNP vs. WTP*Non-TCD (n=94) SNP vs. WTP*Acute GVHD II–IV27 vs. 22N.S22 vs. 40N.S33 vs. 12N.SChronic GVHD61 vs. 350.129 vs. 14N.S100 vs. 440.005Event free survival21 vs. 470.0317 vs. 480.0422 vs. 31N.SOverall survival30 vs. 590.0133 vs. 560.0430 vs. 48N.SWT, wild type; N.S, non significant; * Log-rank test
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