Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR],.79; P =.006) and chronic myelogenous leukemia (CML) (HR,.48; P =.025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR,.97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR,.79, P =.069; unrelated: HR,.77, P =.022), preparative regimen (myeloablative: HR,.79, P =.014; reduced intensity: HR,.73, P =.084), and occurrence of acute graft-versus-host disease (yes: HR,.70, P =.122; no, HR.71, P =.026) or cytomegalovirus reactivation (reactivated: HR.67,P =.054; nonreactivated: HR.71, P =.033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR,.27; P <.001 and HR,.30; P =.002, respectively) and in children age <15 years (HR,.29; P <.001 and HR.31; P <.001, respectively). Our findings represent an important mechanism responsible for the immunity against HLA-C2–negative myeloid leukemia cells after HLA-matched transplantation.
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