Cytomegalovirus Reactivation After Matched Sibling Donor Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplant Correlates With Donor Killer Immunoglobulin-like Receptor Genotype

Abstract

Objectives: cytomegalovirus reactivation is common after reduced-intensity conditioning allogeneic hematopoietic stem cell transplant. Natural killer and T cells mediate immunity against viruses including cytomegalovirus. The alloreactivity of Natural killer cells and some T-cell subsets is mediated through the interaction of their killer immunoglobulin-like receptors with target cell ligands. This study sought to assess whether donor inhibitory or activating killer immunoglobulin-like receptor genotypes may influence post-transplant cytomegalovirus reactivation in transplant recipients.

Materials and Methods: We analyzed 64 patients who underwent T-cell replete, matched sibling donor reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation at our institution. Transplant recipients were categorized according to their HLA inhibitory killer immunoglobulin-like receptor ligand groups. Donor killer immunoglobulin-like receptor genotypes were determined and then were assessed for correlations with cytomegalovirus reactivation in transplant recipients.

Results: No differences in cytomegalovirus reactivation were observed when comparing those with or without missing inhibitory killer immunoglobulin-like receptor ligands. When considering the number of donor activating killer immunoglobulin-like receptor genes, those with 5 or 6 had less cytomegalovirus reactivation than those with 1 to 4 (19% vs 48%; P = .029). The difference could not be attributed to baseline patient or transplant characteristics. No specific activating killer immunoglobulin-like receptor genotype was found to be associated with cytomegalovirus reactivation.

Conclusions: These observations indicate that assessment of donor killer immunoglobulin-like receptor genotype may have important implications for predicting cytomegalovirus reactivation after T-cell replete, matched sibling donor reduced-intensity conditioning allogeneic hematopoietic stem cell transplant.