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Clinical Trial
. 2012 Jun;47(6):817-23.
doi: 10.1038/bmt.2011.181. Epub 2011 Dec 5.

Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors

D-F Chen  1 , V K Prasad, G Broadwater, N L Reinsmoen, A DeOliveira, A Clark, K M Sullivan, J P Chute, M E Horwitz, C Gasparetto, G D Long, Y Yang, N J Chao, D A Rizzieri
Affiliations
Clinical Trial

Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors

D-F Chen et al. Bone Marrow Transplant. 2012 Jun.

Abstract

The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse-related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84 adults with high-risk hematologic malignancies receiving reduced intensity conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical related donors. In this clinical model, freedom from RRM is dependent on GVL effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy groups. KIR-ligand and ligand-ligand models were studied in both GVH and rejection directions and statistically correlated with outcome measures. In the myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1 missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028). There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1, although sample sizes were too small to provide inferential statistics. Findings in lymphoid malignancy patients should be further studied. These results suggest that the absence of appropriate HLA ligands in the recipient to donor iKIR may induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC transplants.

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Figures

Figure 1
Figure 1
Impact of receptor-ligand incompatibility in the GVH/GVL direction on overall survival (OS) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. In this model, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL1 for HLA Bw4 alleles (figure 1A), KIR2DL1 for HLA C2 alleles (figure 1B) that are characterized by lysine at position 80 (HLA-CLys80), KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80), and KIR3DL2 for HLA-A3 and HLA-A11 alleles (graph not shown because of lack of statistical significance). Figure 1C depicts the impact of incompatibility for any of the above locus and figure 1D depicts the impact of multiple incompatibilities.
Figure 1
Figure 1
Impact of receptor-ligand incompatibility in the GVH/GVL direction on overall survival (OS) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. In this model, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL1 for HLA Bw4 alleles (figure 1A), KIR2DL1 for HLA C2 alleles (figure 1B) that are characterized by lysine at position 80 (HLA-CLys80), KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80), and KIR3DL2 for HLA-A3 and HLA-A11 alleles (graph not shown because of lack of statistical significance). Figure 1C depicts the impact of incompatibility for any of the above locus and figure 1D depicts the impact of multiple incompatibilities.
Figure 1
Figure 1
Impact of receptor-ligand incompatibility in the GVH/GVL direction on overall survival (OS) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. In this model, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL1 for HLA Bw4 alleles (figure 1A), KIR2DL1 for HLA C2 alleles (figure 1B) that are characterized by lysine at position 80 (HLA-CLys80), KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80), and KIR3DL2 for HLA-A3 and HLA-A11 alleles (graph not shown because of lack of statistical significance). Figure 1C depicts the impact of incompatibility for any of the above locus and figure 1D depicts the impact of multiple incompatibilities.
Figure 1
Figure 1
Impact of receptor-ligand incompatibility in the GVH/GVL direction on overall survival (OS) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. In this model, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL1 for HLA Bw4 alleles (figure 1A), KIR2DL1 for HLA C2 alleles (figure 1B) that are characterized by lysine at position 80 (HLA-CLys80), KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80), and KIR3DL2 for HLA-A3 and HLA-A11 alleles (graph not shown because of lack of statistical significance). Figure 1C depicts the impact of incompatibility for any of the above locus and figure 1D depicts the impact of multiple incompatibilities.
Figure 2
Figure 2
Impact of receptor-ligand incompatibility in the GVH/GVL direction on relapse related mortality (RRM) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. Similar to figure 1, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL2 for HLA-A3 and HLA-A11 alleles (figure 2A), KIR2DL1 for HLA C2 alleles (figure 2B) that are characterized by lysine at position 80 (HLA-CLys80), KIR3DL1 for HLA Bw4 alleles (graph not shown because of lack of statistical significance), and KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80). Figure 2C depicts the combined impact of incompatibility for any of the above loci.
Figure 2
Figure 2
Impact of receptor-ligand incompatibility in the GVH/GVL direction on relapse related mortality (RRM) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. Similar to figure 1, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL2 for HLA-A3 and HLA-A11 alleles (figure 2A), KIR2DL1 for HLA C2 alleles (figure 2B) that are characterized by lysine at position 80 (HLA-CLys80), KIR3DL1 for HLA Bw4 alleles (graph not shown because of lack of statistical significance), and KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80). Figure 2C depicts the combined impact of incompatibility for any of the above loci.
Figure 2
Figure 2
Impact of receptor-ligand incompatibility in the GVH/GVL direction on relapse related mortality (RRM) in patients with myeloid malignancy undergoing T cell depleted reduced intensity conditioning related donor haploidentical transplantation. Similar to figure 1, incompatibility is defined as absence of corresponding ligand in the recipient to the inhibitory KIR present in the donor. The combinations used were KIR3DL2 for HLA-A3 and HLA-A11 alleles (figure 2A), KIR2DL1 for HLA C2 alleles (figure 2B) that are characterized by lysine at position 80 (HLA-CLys80), KIR3DL1 for HLA Bw4 alleles (graph not shown because of lack of statistical significance), and KIR2DL2 and KIR2DL3 for HLA C1 alleles (graph not shown because of lack of statistical significance) characterized by Asparagine at position 80 (HLA-CAsn80). Figure 2C depicts the combined impact of incompatibility for any of the above loci.
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References

    1. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002 Mar 15;295(5562):2097–100. - PubMed
    1. Hale G, Zhang MJ, Bunjes D, Prentice HG, Spence D, Horowitz MM, et al. Improving the Outcome of Bone Marrow Transplantation by Using CD52 Monoclonal Antibodies to Prevent Graft-Versus-Host Disease and Graft Rejection. Blood. 1998 Dec 15;92(12):4581–90. - PubMed
    1. Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G, et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood. 2004 Dec 15;104(13):3865–71. - PubMed
    1. Rizzieri DA, Koh LP, Long GD, Gasparetto C, Sullivan KM, Horwitz M, et al. Partially Matched, Nonmyeloablative Allogeneic Transplantation: Clinical Outcomes and Immune Reconstitution. J Clin Oncol. 2007 Feb 20;25(6):690–7. - PubMed
    1. Barrett AJ. Understanding and harnessing the graft-versus-leukaemia effect. Br J Haematol. 2008 Sep;142(6):877–88. - PubMed

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