Is there an impact of killer cell immunoglobulin-like receptors and KIR-ligand incompatibilities on outcomes after unrelated cord blood stem cell transplantation?

Abstract

Donor killer cell immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction is associated with decreased relapse incidence and improved disease-free survival after haploidentical and human leucocyte antigen (HLA)-mismatched unrelated, haematopoietic stem cell transplantation. However, review of all published studies of allogeneic HLA-matched or mismatched stem cell transplantation shows that the results on the relationship between donor-recipient KIR(-ligand) (in)compatibility and outcomes are highly variable, ranging from highly beneficial to detrimental. Reasons for these differences may include the methodology to determine KIR(-ligand) incompatibility, the disease distribution and the transplant protocol or donor type. Two retrospective studies on the effects of KIR-ligand incompatibility in unrelated cord blood transplantation (UCBT) for haematological malignancies have resulted in conflicting results. The Eurocord study showed a favourable effect of KIR-ligand mismatching on relapse incidence and leukaemia-free survival, whereas the Minneapolis study showed no effect on these end points and a detrimental effect on incidence of graft-versus-host disease (GvHD). In patients with non-malignant disorders, KIR-ligand (in)compatibility between donor and recipient was not associated with outcomes in a recent Eurocord analysis. Therefore, the role of natural killer (NK) cell alloreactivity in UCBT is far from clear. It is too early to use a donor-recipient KIR(-ligand) algorithm for selection of a cord blood donor.