Biology of Blood and Marrow Transplantation
Volume 12, Issue 8 , Pages 876-884 , August 2006

The Effect of KIR Ligand Incompatibility on the Outcome of Unrelated Donor Transplantation: A Report from the Center for International Blood and Marrow Transplant Research, the European Blood and Marrow Transplant Registry, and the Dutch Registry

  • Sherif S. Farag

      Affiliations

    • The Ohio State University, Columbus, Ohio
    • Corresponding Author InformationCorrespondence and reprint requests: Dr. Sherif S. Farag, Department of Internal Medicine, Division of Hematology and Oncology and The Comprehensive Cancer Center, The Ohio State University, A433A Starling-Loving Hall, 320 West Tenth Avenue, Columbus, OH 43210
    • ,
  • Andrea Bacigalupo

      Affiliations

    • Ospedale S. Martino, Genova, Italy
    • ,
  • Mary Eapen

      Affiliations

    • Statistical Center, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin
    • ,
  • Carolyn Hurley

      Affiliations

    • Georgetown University School of Medicine, Washington, DC
    • ,
  • Bo Dupont

      Affiliations

    • Memorial Sloan-Kettering Cancer Center, New York, New York
    • ,
  • Michael A. Caligiuri

      Affiliations

    • The Ohio State University, Columbus, Ohio
    • ,
  • Christian Boudreau

      Affiliations

    • University of Waterloo, Waterloo, Ontario, Canada
    • ,
  • Gene Nelson

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Machteld Oudshoorn

      Affiliations

    • Leiden University Medical Center, Europdonor Foundation, Leiden, The Netherlands
    • ,
  • Jon van Rood

      Affiliations

    • Leiden University Medical Center, Europdonor Foundation, Leiden, The Netherlands
    • ,
  • Andrea Velardi

      Affiliations

    • Policlinico di Monteluce, Perugia, Italy
    • ,
  • Martin Maiers

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Michelle Setterholm

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Dennis Confer

      Affiliations

    • National Marrow Donor Program, Minneapolis, Minnesota
    • ,
  • Phillip E. Posch

      Affiliations

    • Georgetown University School of Medicine, Washington, DC
    • ,
  • Claudio Anasetti

      Affiliations

    • H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
    • ,
  • Naynesh Kamani

      Affiliations

    • Children’s National Medical Center, Washington, DC
    • ,
  • Jeffrey S. Miller

      Affiliations

    • University of Minnesota, Minneapolis, Minnesota
    • ,
  • Daniel Weisdorf

      Affiliations

    • University of Minnesota, Minneapolis, Minnesota
    • ,
  • Stella M. Davies

      Affiliations

    • Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
    • ,
  • KIR Study Group, Center for International Blood and Marrow Transplantation Research

Received 23 February 2006 ,Accepted 17 May 2006.

References 

  1. Davies SM , Kollman C , Anasetti C , et al.   Engraftment and survival after unrelated-donor bone marrow transplantation (a report from the National Marrow Donor Program) . Blood . 2000;96:4096–4102
  2. McGlave PB , Shu XO , Wen W , et al.   Unrelated donor marrow transplantation for chronic myelogenous leukemia (9 years’ experience of the National Marrow Donor Program) . Blood . 2000;95:2219–2225
  3. Sasazuki T , Juji T , Morishima Y , et al.   Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor . N Engl J Med . 1998;339:1177–1185
  4. Petersdorf EW , Longton GM , Anasetti C , et al.   Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors . Blood . 1997;89:1818–1823
  5. Szydlo R , Goldman JM , Klein JP , et al.   Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings . J Clin Oncol . 1997;15:1767–1777
  6. Flomemberg N , Baxter-Lowe LA , Confer D , et al.   Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation (HLA-C mismatching is associated with a strong adverse effect on transplantation outcome) . Blood . 2004;104:1923–1930
  7. Lanier LL . NK cell receptors . Annu Rev Immunol . 1998;16:359–393
  8. Farag SS , Fehniger TA , Ruggeri L , et al.   Natural killer cell receptors (new biology and insights into the graft-versus-leukemia effect) . Blood . 2002;100:1935–1947
  9. Ruggeri L , Capanni M , Casucci M , et al.   Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation . Blood . 1999;94:333–339
  10. Ruggeri L , Capanni M , Urbani E , et al.   Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants . Science . 2002;295:2097–2100
  11. Aversa F , Terenzi A , Tabilio A , et al.   Full haplotype-mismatched hematopoietic stem-cell transplantation (a phase II study in patients with acute leukemia at high risk of relapse) . J Clin Oncol . 2005;23:3447–3457
  12. Geibel S , Locatelli F , Maccario R , et al.   Survival advantage with KIR ligand incompatibility in unrelated donor transplantation . Blood . 2003;102:814–819
  13. Davies SM , Ruggeri L , DeFor T , et al.   Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants (killer immunoglobulin-like receptor) . Blood . 2002;100:3825–3827
  14. Bennett JM , Catovsky D , Daniel MT , et al.   Proposed revised criteria for the classification of acute myeloid leukemia (a report of the French-American-British Cooperative Group) . Ann Intern Med . 1985;103:620–625
  15. Bennett JM , Catovsky D , Daniel MT , et al.   Proposals for the classification of the myelodysplastic syndromes . Br J Haematol . 1982;51:189–199
  16. Przepiorka D , Weisdorf D , Martin P , et al.   1994 consensus conference on acute GVHD grading chronic graft-versus-host syndrome in man (a long-term clinicopathologic study of 20 Seattle patients) . Bone Marrow Transplant . 1995;15:825–828
  17. Shulman HM , Sullivan KM , Weiden PL , et al.   Chronic graft-versus-host syndrome in man (a long-term clinicopathologic study of 20 Seattle patients) . Am J Med . 1980;69:204–217
  18. Kaplan EL , Meier P . Nonparametric estimation from incomplete observations . J Am Stat Assoc . 1998;16:1141–1154
  19. Gooley TA , Leisenring W , Crowley J , et al.   Estimation of failure probabilities in the presence of competing risks (new representations of old estimators) . Stat Med . 1999;18:695–706
  20. Cox DR . Regression models and life tables (with discussion) . J R Stat Soc B . 1972;34:187–220
  21. Bishara A , De Santis D , Witt CC , et al.   The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD . Tissue Antigens . 2004;63:204–211
  22. Lowe EJ , Turner V , Handgretinger R , et al.   T-cell alloreactivity dominates natural killer cell alloreactivity in minimally T-cell–depleted HLA-nonidentical paediatric bone marrow transplantation . Br J Haematol . 2003;123:323–326
  23. Beelen DW , Ottinger HD , Ferencik S , et al.   Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias . Blood . 2005;105:2594–2600
  24. Schaffer M , Malmberg KJ , Ringden O , et al.   Increased infection-related mortality in KIR ligand-mismatched unrelated allogeneic hematopoietic stem-cell transplantation . Transplantation . 2004;78:1081–1085
  25. Cooley S , McCullar V , Wangen R , et al.   KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation . Blood . 2005;106:4370–4376
  26. Gumperz JE , Valiante NM , Parham P , et al.   Heterogeneous phenotypes of expression of the NKB1 natural killer cell class I receptor among individuals of different human histocompatibility leukocyte antigens types appear genetically regulated, but not linked to major histocompatibililty complex haplotype . J Exp Med . 1996;183:1817–1827
  27. Frohn C , Schlenke P , Kirchner H . The repertoire of HLA-Cw–specific NK cell receptors CD158 a/b (EB6 and GL183) in individuals with different HLA phenotypes . Immunology . 1997;92:567–570
  28. Vilches C , Parham P . KIR (diverse, rapidly evolving receptors of innate and adaptive immunity) . Ann Rev Immunol . 2002;20:217–251
  29. Parham P , McQueen KL . Alloreactive killer cells (hindrance and help for haematopoietic transplants) . Nat Rev Immunol . 2003;3:108–122
  30. Dupont B , Hsu KC . Inhibitory killer Ig-like receptor genes and human leukocyte antigen class I ligands in haematopoietic stem cell transplantation . Curr Opin Immunol . 2004;16:634–643
  31. Leung W , Iyengar R , Turner V , et al.   Determinants of antileukemia effects of allogeneic NK cells . J Immunol . 2004;172:644–650
  32. Hsu KC , Keever-Taylor CA , Wilton A , et al.   Improved outcome in HLA-identical sibling hematopoietic stem cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes . Blood . 2005;105:4878–4884
  33. Gagne K  . Relevance of KIR gene polymorphisms in bone marrow transplantation outcome . Hum Immunol . 2002;63:271–280
  34. Bishara A , De Santis D , Witt CC , et al.   The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD . Tissue Antigens . 2004;63:204–211
  35. De Santis D , Bishara A , Witt CC , et al.   Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants . Tissue Antigens . 2005;65:519–528
  36. Cook MA , Milligan DW , Fegan CD , et al.   The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia . Blood . 2004;103:1521–1526

PII: S1083-8791(06)00374-0

doi: 10.1016/j.bbmt.2006.05.007

Biology of Blood and Marrow Transplantation
Volume 12, Issue 8 , Pages 876-884 , August 2006

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