Prognosis after unmanipulated HLA-haploidentical blood and marrow transplantation is correlated to the numbers of KIR ligands in recipients

OBJECTIVES: The goal of this study was to explore the role of NK cell alloreaction in predicting prognosis under unmanipulated HLA-haploidentical blood and marrow transplantation and examine whether the presence of any individual donor-activating KIR gene had an influence on the clinical outcome. METHODS: We studied the HLA and KIR genotype of 64 donor-recipient pairs, who underwent transplantation. RESULTS: In contrast to Perugia's KIR ligand-ligand mismatch model or Handgretinger's KIR receptor-ligand mismatch model or Bignon's KIR gene-gene mismatch model between donor-recipient pairs, we found that the cumulative incidence of 3-yr disease-free survival (DFS), overall survival (OS), and transplantation-related mortality (TRM) were best predicted by the number of KIR ligands carried by patients (HR 0.355, 95% CI 0.186-0.678, P = 0.002 for DFS; HR 0.445, 95% CI 0.233-0.848, P = 0.014 for OS; HR 0.450, 95% CI 0.219-0.926, P = 0.030 for TRM). Moreover, an analysis of KIR ligand numbers was found to be correlative in patients with lymphoid malignancy. The KIR ligand-ligand mismatch model is a good predictor of acute graft vs. host disease (aGVHD; HR 3.812, 95% CI 1.667-8.720, P = 0.002). Meanwhile, the presence of donor-activating KIR2DS3 also contributed significantly to acute (HR 2.967, 95% CI 1.265-6.958, P = 0.012) and chronic GVHD (HR 2.541, 95% CI 1.127-5.730, P = 0.025). CONCLUSIONS: These data indicate that prognosis after transplantation is associated with the numbers of KIR ligands in recipients and T-cell alloreaction may play a predominant role in this model.