Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia

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. (C) 2017 American Society for Blood and Marrow Transplantation.