Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors.

Killer immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction was demonstrated to be associated with improved outcome in patients given haploidentical, T-cell-depleted hematopoietic stem cell transplants (HSCTs). The goal of this study was to evaluate whether that observation could be generalized for patients receiving unmanipulated HSCTs from unrelated donors (URD). One hundred thirty patients with hematologic malignancies entered the study. Graft-versus-host disease (GVHD) prophylaxis was uniform and consisted of cyclosporin, short-term methotrexate, and pretransplantation antithymocyte globulin (ATG). Patients were divided into those with (n = 20) and those without (n = 110) KIR ligand incompatibility with respect to their donors. At 4.5 years patients with KIR ligand incompatibility had higher probability of overall survival (87% versus 48%, P =.006) and disease-free survival (87% versus 39%, P =.0007) compared with those without KIR ligand incompatibility. Transplant-related mortality for the 2 groups equaled 6% and 40% (P =.01), respectively. Relapse rates for patients receiving transplants from a donor with or without KIR ligand incompatibility were 6% and 21%, respectively (P =.07). All patients with myeloid malignancies receiving transplants from KIR ligand-disparate donors (n = 13) are alive and disease free. These data indicate that natural killer (NK) cell alloreactivity is associated with better outcome after URD-HSC transplantation when ATG is used as part of GVHD prophylaxis.

[1]  J Crowley,et al.  Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. , 1999, Statistics in medicine.

[2]  J. Ritz,et al.  Biology and clinical relevance of human natural killer cells. , 1990, Blood.

[3]  Todd A Fehniger,et al.  Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. , 2002, Blood.

[4]  H. Deeg,et al.  Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings. , 1983, Annals of internal medicine.

[5]  M. Shlomchik,et al.  Prevention of graft versus host disease by inactivation of host antigen-presenting cells. , 1999, Science.

[6]  K. Kärre.  A Perfect Mismatch , 2002, Science.

[7]  Daniel J Weisdorf,et al.  Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor. , 2002, Blood.

[8]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[9]  Katia Perruccio,et al.  Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants , 2002, Science.

[10]  K. Kärre.  Immunology. A perfect mismatch. , 2002, Science.

[11]  A. Pession,et al.  Extracorporeal photochemotherapy for treatmentof acute and chronic GVHD in childhood , 2001, Transfusion.

[12]  P. Bruzzi,et al.  Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). , 2001, Blood.

[13]  F. Locatelli,et al.  Low incidence of severe acute graft-versus-host disease in children given haematopoietic stem cell transplantation from unrelated donors prospectively matched for HLA class I and II alleles with high-resolution molecular typing , 2003, Bone Marrow Transplantation.

[14]  A. Tosti,et al.  Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. , 1999, Blood.

[15]  P. Neiman,et al.  CLINICAL MANIFESTATIONS OF GRAFT‐VERSUS-HOST DISEASE IN HUMAN RECIPIENTS OF MARROW FROM HL‐A-MATCHED SIBLING DONOR,S , 1974, Transplantation.