Decreased infections in recipients of unrelated donor hematopoietic cell transplantation from donors with an activating KIR genotype

Abstract

Infectious complications following allogeneic hematopoietic cell transplantation (HCT) from unrelated donors (URD) result in significant morbidity. We hypothesized that recipients of a URD with an activating natural killer cell immunoglobulin-like receptor (KIR) (B/x) genotype would have decreased infectious complications because of enhanced natural killer (NK) cell function. We compared the infectious complications in 116 recipients of a graft from a donor with an A/A KIR (n = 44) genotype and a B/x KIR (n = 72) genotype. All recipients participated in the prospective National Marrow Donor Program infection project collecting infection data from conditioning until 6 months posttransplant. The cohort with a B/x donor had fewer initial bacterial infections by day 180 (A/A: 86%; 95% confidence interval [CI], 75-95; B/x: 68%; 95% CI, 57-78; P = .02). There was no difference in the incidence of viral or fungal infections. When accounting for multiple infections, fewer bacterial infections were seen in the B/x cohort (A/A: 3.55/patient; B/x: 2.63/patient; P = .09). During the study period, only 19 patients had no infections; of these, 15 had received cells from a B/x KIR donor. The role of donor KIR genotype on infection complications is intriguing and warrants further investigation.

Figure 1

Mean number of infections during the first 180 days following HCT. The mean number of infections is shown as the infection density defined as the number of infections per patient per days at risk and normalized over the 180 study period.

Figure 2

The cumulative incidence of bacterial infections in recipients of a KIR A/A genotype and a KIR B/x genotype unrelated donor graft.

Figure 3

The adjusted relative infection density for a KIR A/A (dotted bar) donor recipient as compared to a KIR B/x (line) donor recipient during the first 180 days. A value above 1.0 indicates a higher mean ratio of infections in the KIR A/A cohort.