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Allografting

Influence of killer immunoglobulin-like receptor/HLA ligand matching on achievement of T-cell complete donor chimerism in related donor nonmyeloablative allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 41, pages 709–714 (2008)Cite this article

Abstract

Achievement of complete donor chimerism (CDC) after allogeneic nonmyeloablative hematopoietic stem cell transplantation (NMHSCT) is important for preventing graft rejection and for generating a graft-vs-malignancy effect. The alloreactivity of NK cells and some T-cell subsets is mediated through the interaction of their killer immunoglobulin-like receptors (KIRs) with target cell HLA/KIR ligands. The influence of KIR matching on the achievement of T-cell CDC after NMHSCT has not been previously described. We analyzed 31 patients undergoing T-cell replete related donor NMHSCT following fludarabine and 200 cGy TBI. Recipient inhibitory KIR genotype and donor HLA/KIR ligand matches were used to generate an inhibitory KIR score from 1 to 4 based upon the potential number of recipient inhibitory KIRs that could be engaged with donor HLA/KIR ligands. Patients with a score of 1 were less likely to achieve T-cell CDC (P=0.016) and more likely to develop graft rejection (P=0.011) than those with scores greater than 1. Thus, patients with lower inhibitory KIR scores may have more active anti-donor immune effector cells that may reduce donor chimerism. Conversely, patients with greater inhibitory KIR scores may have less active NK cell and T-cell populations, which may make them more likely to achieve CDC.

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Authors and Affiliations

  1. Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA

    R M Sobecks, S Brown, M Kalaycio, S Andresen, B Pohlman, R Dean, J Sweetenham, L Bernhard, K Cherni, E Copelan & B J Bolwell

  2. Department of Pathology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada

    E J Ball

  3. Allogen Laboratories, The Cleveland Clinic, Cleveland, OH, USA

    M Askar & D Thomas

  4. Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA

    K S Theil

  5. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    L A Rybicki

  6. Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA

    R Macklis

  7. Experimental Hematology and Hematopoiesis, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA

    J P Maciejewski

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  1. R M Sobecks
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  2. E J Ball
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  8. M Kalaycio
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Correspondence to R M Sobecks.

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Sobecks, R., Ball, E., Askar, M. et al. Influence of killer immunoglobulin-like receptor/HLA ligand matching on achievement of T-cell complete donor chimerism in related donor nonmyeloablative allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 41, 709–714 (2008). https://doi.org/10.1038/sj.bmt.1705954

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  • DOI: https://doi.org/10.1038/sj.bmt.1705954

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