The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population

Abstract

The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donorrecipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P ¼ 0.019, HR ¼ 0.329), mainly in myeloid disease (P ¼ 0.003, HR ¼ 0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P ¼ 0.034, HR ¼ 0.430) and disease-free survival (DFS) (P ¼ 0.024, HR ¼ 0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P ¼ 0.003, HR ¼ 5.046), decreased OS (P ¼ 0.004, HR ¼ 3.181) and DFS (P ¼ 0.003, HR ¼ 2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.

KIR Genes and Patterns Given by the A Priori Algorithm: Immunity for Haematological Malignancies

“…Nevertheless, the ID3 algorithm failed to find associations related to the KIR2DS3, as described previously by others researchers [ 35 – 37 ]. Neither KIR2DL1 nor KIR2DL3 are on their own important factors in the ID3 decision processes [ 33 ].…”

“…Some researchers have reported some associations related to KIR2DS3 [ 35 – 37 ]. The rules shown in Table 7 (Class = 1) are only associated to disease ( C = 1) with the absence of KIR2DS3.…”

Influence of KIR and NK Cell Reconstitution in the Outcomes of Hematopoietic Stem Cell Transplantation

“…Other factors, such as HLA mismatch, disease type, patient age, GVHD prophylaxis, and graft source, were also reported to interfere with GVHD occurrence in these studies ( 44 , 45 , 63 , 66 , 87 , 92 , 93 , 104 ). Collectively, the manner in which the reconstituted NK cells affect the risk of GVHD remains largely unknown, and the relationships between NK and T cells during the initiation and process of GVHD warrant further investigation.…”

“…In addition to the technique of adoptive transfer, many studies have analyzed the effects of innate donor-recipient NK cell alloreactivity on GVHD in a clinical setting. The majority of studies did not report a significant association between these parameters ( 41 – 44 , 46 , 47 , 50 , 51 , 54 – 56 , 59 , 65 , 66 , 79 , 81 , 83 , 87 – 89 , 91 – 93 , 97 , 98 , 102 , 104 ), while some reported a protective effect ( 70 , 74 , 76 ). Moreover, several studies found that KIR ligand mismatch or receptor-ligand mismatch increased the risk of GVHD ( 45 , 57 , 60 , 64 , 68 , 80 ).…”

Interactions between killer immunoglobulin‐like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm

“…It is widely accepted that activating KIR genes have a fundamental role in HSCT outcome (Venstrom et al , 2010; Wu et al , 2010). Individuals with several activating KIR genes have a higher probability of expressing activating KIRs on NK cells.…”