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Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing  NKG2C  have been shown to play a role in the immune surveillance of human CMV. We studied  NKG2C  copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts ( n  = 200). In the setting of DUCBT, the combined graft may contain 0–4 functional copies of  NKG2C  gene. Sixteen patients received a combined graft with 1 or 2  NKG2C  copies and 84 patients were recipients of a combined graft with 3 or 4  NKG2C  copies. The 6-month cumulative incidence of CMV reactivation for the two groups was 93.7 and 58.4%, respectively ( p  = 0.0003). In multivariate analysis, low  NKG2C  copies in the graft was an independent predictor of CMV reactivation (HR = 2.72, CI = 1.59–4.64;  p  < 0.0001). Our study points to an important role for donor  NKG2C  for protection against CMV reactivation after DUCBT. These novel findings may help identify patients at a higher risk of CMV reactivation after DUCBT. Donor  NKG2C  genotype may be used as a potential criterion in the algorithm for graft selection for DUCBT.

Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation