Relevance of KIR gene polymorphisms in bone marrow transplantation outcome

Gagne, Katia; Brizard, Géraldine; Gueglio, B.; Milpied, Noël; Herry, P.; Bonneville, Françoise; Chéneau, Mary Luce; Schleinitz, N.; Cesbron, Anne; Folléa, Gilles; Harrousseau, Jean Luc; Bignon, J.

doi:10.1016/s0198-8859(02)00373-7

Cited by 140 publications

(143 citation statements)

References 32 publications

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“…36 However, for patients receiving unrelated transplants, donor KIR2DS3 has been reported to increase aGVHD. 39 In our study, we did not find any association between this gene and aGVHD in unrelated transplantation. These conflicting results are difficult to explain, as the function and ligand specificity of KIR2DS3 have to date not been identified.…”

Section: Discussioncontrasting

confidence: 61%

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

Zhao

Lai

et al. 2010

Bone Marrow Transplant

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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.

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Section: Discussioncontrasting

confidence: 61%

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

Zhao

Lai

et al. 2010

Bone Marrow Transplant

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“…8 The aKIR in donors was considered a potential high-risk marker for aGVHD. 9 Our results showed that 2DS4 full-length allele, as the only aKIR gene in donor, was closely related with an increasing risk of aGVHD, especially III-IV aGVHD, in group A/A. 33 When donors possessed two 2DS4-full alleles, there might be more functional activating receptors on their NK cells compared with those who possessed less 2DS4-full alleles.…”

Section: Discussionmentioning

confidence: 61%

“…Chen et al 8 reported that presence of more aKIR genes in donors were associated with a lower transplant-related mortality (TRM) and a better survival. However, this NK reactivity may also have a negative effect on outcome: Gagne et al 9 reported an increase of GVHD in unrelated transplantations when the donor has more aKIR. These data highlight the effect of donor-aKIR genes in allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

The impact of KIR2DS4 alleles and the expression of KIR in the development of acute GVHD after unrelated allogeneic hematopoietic SCT

Bao

Hou

Sun

et al. 2010

Bone Marrow Transplant

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“…This is, to our knowledge, the first observation of a protective effect of the KIR2DS2 on aGVHD (II-IV). Regarding the role of activatory KIR genes in transplantation, Gagne et al 29 have reported that KIR2DS3 in donors is a potential high risk marker for aGVHD. Also, donor's KIR2DS2 was shown to be associated with worse OS in HLA-C2C2 patients with myeloid leukemia.…”

Section: Discussionmentioning

confidence: 99%

KIR genes and KIR ligands affect occurrence of acute GVHD after unrelated, 12/12 HLA matched, hematopoietic stem cell transplantation

Ludajic

Balavarca

Bickeböller

et al. 2009

Bone Marrow Transplant

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Interactions of polymorphic killer Ig-like receptor (KIR) receptors with KIR ligands have been shown to modify the outcome of hematopoietic SCT (HSCT). The association of these genetic factors with different transplantation endpoints, however, varies substantially, depending on clinical and study setup variables. We aimed to assess whether KIR ligands, KIR genes and KIR haplotypes are associated with HSCT outcome of 124 patients with various hematological malignancies, transplanted with 12/ 12 HLA matched grafts from unrelated donors. For this purpose, patient and donor KIR gene and KIR ligand polymorphisms were determined and correlated with clinical data in simple and multiple models. We found that a missing HLA-C2 ligand for donor inhibitory KIR2DL1 was significantly associated with an increased risk of acute GVHD (aGVHD) (II-IV) (hazard ratio (HR) ¼ 2.23, 95% confidence interval (95% CI): 1.21-4.10, P ¼ 0.010), as were the AA KIR haplotypes in patients and donors in HLA-C1CX (HR ¼ 2.37, 95% CI: 1.16-4.84, P ¼ 0.018) and in HLA-Bw4 À (HR ¼ 3.20, 95% CI: 1.35-7.60, P ¼ 0.008) patients. On the contrary, transplantation of HLA-C1C2 patients with KIR2DS2 positive grafts were associated with a decreased risk of aGVHD (II-IV) (HR ¼ 0.24, 95% CI: 0.07-0.85, P ¼ 0.027). Thus, our single center study provides evidence for the modification of aGVHD risk by KIRs and their ligands.

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Relevance of KIR gene polymorphisms in bone marrow transplantation outcome

Cited by 140 publications

References 32 publications

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

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

The impact of KIR2DS4 alleles and the expression of KIR in the development of acute GVHD after unrelated allogeneic hematopoietic SCT

KIR genes and KIR ligands affect occurrence of acute GVHD after unrelated, 12/12 HLA matched, hematopoietic stem cell transplantation

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