Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Summary Licensed natural killer ( NK ) cells have been demonstrated to have anti‐cytomegalovirus ( CMV ) activity. We prospectively analysed the human leucocyte antigen typing of donor‐recipient pairs and the killer cell immunoglobulin–like receptor ( KIR ) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post‐T‐cell‐replete haploidentical stem cell transplantation. Multivariate analysis showed that donor‐recipient KIR ligand graft‐versus‐host or host‐versus‐graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377–4·744, P = 0·003) post‐transplantation. Donor‐recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post‐transplantation. In addition, the percentage of γ‐interferon expression on donor‐derived NK cells was significantly higher in the recipients among the recipient‐donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft‐versus‐host or host‐versus‐graft direction mismatch on days 30 and 100 post‐transplantation ( P = 0·036 and 0·047, respectively). These findings have suggested that donor‐recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell‐mediated protection against CMV reactivation.