SALT LAKE CITY – The presence of p2X7 receptor single nucleotide polymorphisms (SNPs) associated with gain and loss of function may help predict outcomes after allogeneic stem cell transplantation, according to findings from a clinical correlate analysis of recipient and donor DNA samples.
The findings require validation in future studies, but suggest that the presence of the SNPs and p2X7 haplotypes 2 and 4 could be incorporated into disease risk models to improve transplant decision making, David Stuart Ritchie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The analysis, which specifically looked for the presence of 16 previously identified SNPs and the haplotypes 2 and 4 in p2x7, was performed on pretransplant DNA samples from 333 allogeneic stem cell transplant recipients and 228 donors at a single center between 2002 and 2013. The findings were correlated with patient outcomes.
Five SNPs were excluded from correlation because of low frequency, and of the 11 remaining SNPs, 3 were found to be significantly associated with reduced incidence of acute and/or chronic graft-versus-host disease (GVHD), and 2 were significantly associated with increased relapse or transplant-related mortality, said Dr. Ritchie of the University of Melbourne, Parkville, Australia.
The loss-of-function SNPs rs28360457 and rs3751133 – each linked with decreased inflammation – were significantly associated with a reduced incidence of acute GVHD when comparing grade 0 with grades 1-4 GVHD (P = .0234 and P = .0411, respectively), but not when comparing grades 0-1 and grades 2-4 GVHD.
SNP rs3751133 was also significantly associated with reduced incidence of chronic GVHD when comparing grade 0 with grades 0-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD, he said.
The loss-of-function SNP rs1653624 – which is linked with decreased phagocytosis – was associated with an increased incidence of acute GVHD when comparing grade 0 vs. grade 1-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD (P = NS).