KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy.
Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval, .043-0.85; P = .004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P = .004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P = .04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P = .95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants.
Hsu
Katharine C
KC
Adult Allogeneic Bone Marrow Transplantation Service, Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. hsuk@mskcc.org
Gooley
Ted
T
Malkki
Mari
M
Pinto-Agnello
Clara
C
Dupont
Bo
B
Bignon
Jean-Denis
JD
Bornhäuser
Martin
M
Christiansen
Frank
F
Gratwohl
Alois
A
Morishima
Yasuo
Y
Oudshoorn
Machteld
M
Ringden
Olle
O
van Rood
Jon J
JJ
Petersdorf
Effie
E
D018572:Disease-Free Survival; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007519:Isoantigens / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D019520:Living Donors; D017710:Lymphocyte Transfusion / Q000401:mortality; D008297:Male; D011971:Receptors, Immunologic / Q000819:agonists / Q000235:genetics / Q000276:immunology; D054340:Receptors, KIR; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D000939:Epitopes; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; D007519:Isoantigens; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR