Donor KIR Genotype Does Not Affect VZV Reactivation after Allogeneic Haematopoietic Stem Cell Transplantation.

Background. Varicella zoster virus (VZV) reactivation is a common occurrence after allogeneic haematopoietic stem cell transplant (HSCT) and a cause of significant morbidity. We have recently demonstrated the protective effect of donor KIR genotpye against cytomegalovirus (CMV) reactivation- specifically the protective effect of the broad ’B’ haplotype containing multiple activating KIR genes¹. This retrospective study was designed to investigate whether donor KIR genotype confers an equivalent protective effect against VZV reactivation.

Method. 152 patients who underwent allogeneic HSCT at a single centre were identified. Those with pre-transplant serology consistent with previous exposure to VZV were defined as at risk of VZV reactivation. All patients received aciclovir 800mg daily as routine prophylaxis. The diagnosis of VZV reactivation was made clinically. Cases of VZV reactivation were identified by examination of the case records. KIR genotyping was performed on donor DNA using PCR-SSP. The individual KIR genes KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5 and 3DS1, as well as the broad KIR haplotypes ’A’ and ’B’, were assessed by univariate and multivariate analysis for an effect on VZV reactivation. Also assessed was the impact of recipient HLA-C type, recipient HLA-Bw4/Bw6, donor type (sex-matched sibling, sex-mismatched sibling, volunteer unrelated), reduced intensity conditioning (RIC) regimen, the use of alemtuzemab as in vivo T cell depletion, CMV reactivation, and grade 2 or greater GVHD requiring steroid therapy.

Results. 128 (84.2%) patients had evidence of past infection and thus were deemed at risk of VZV reactivation. Of these, 47 (36.7%) had clinical evidence of reactivation. 60% of transplants were from a donor possessing the broad ’B’ haplotype. The rate of reactivation in the presence of donor ’B’ haplotype was 40% compared to 32% when no donor ’B’ haplotype was present (p=0.237). None of the individual donor KIRs were shown to significantly reduce the rate of VZV reactivation. Neither the use of a RIC regimen nor the presence of alemtuzemab in the conditioning regimen were shown to have an impact. None of the other factors analysed were associated with an increased rate of zoster reactivation.

Conclusion. Donor KIR genotype does not influence VZV reactivation after allogeneic HSCT. This contrasts with the findings for CMV reactivation. No influence of donor type, conditioning or GVHD could be demonstrated. This suggests 1) that there are differing mechanisms that control the reactivation of different Herpes viruses after transplantation and 2) that KIRs may have specificity for CMV.