Detrimental Effect of Natural Killer Cell Alloreactivity in T-replete Hematopoietic Cell Transplantation (HCT) for Leukemia Patients

In hematopoietic cell transplantation (HCT), natural killer cell alloreactivity conferred by inhibitory ligands of killer immunoglobulin-like receptors (iKIRLs) may result in beneficial or detrimental outcomes. More data may contribute to resolution of this complex issue. We analyzed 378 primary allogeneic transplants with T-replete grafts for acute lymphoblastic leukemia (n = 101), acute myeloid leukemia and myelodysplastic syndrome (n = 149), and chronic myeloid leukemia (n = 128). The cohort was divided into 3 groups: in group 1, HLA class I matched at the antigen level (n = 260); in group 2, HLA class I mismatched at the antigen level (n = 57); and in group 3, HLA class I and iKIRLs mismatched (n = 61). One-year overall survival (OS) across groups 1 (59%), 2 (49%), and 3 (30%) was significantly different (P = .002). In contrast to group 2, group 3 had statistically lower OS (P = .05) and event-free survival (P = .01). Relapse and relapse-free mortality appeared to contribute to the low OS in group 3. The detrimental effect of natural killer alloreactivity was also evident when HLA-matched transplants were analyzed for patients lacking iKIRLs. One-year OS in patients lacking the HLA-Cw group 1 or 2 iKIRL was significantly lower than that in patients having the iKIRLs (55% vs 67%, n = 246, P = .01). Our observations indicate that, in T-replete unrelated HCT, iKIRL mismatches and the absence of iKIRLs confer higher risk to patients after HCT.