Inhibitory KIR-HLA receptor-ligand mismatch in autologous haematopoietic stem cell transplantation for solid tumour and lymphoma.
Genes that encode killer Ig-like receptors (KIRs) and their HLA class I ligands segregate independently; thus, some individuals may express an inhibitory KIR gene but not its cognate ligand. We hypothesised that these patients with KIR-HLA receptor-ligand mismatch have a low risk of relapse after an autologous haematopoietic stem cell transplantation (HCT). Sixteen consecutive patients with lymphoma or solid tumour were enrolled onto a prospective study. They received high-dose busulphan and melphalan followed by autologous CD133(+) HCT. We found that 8 of the 16 patients experienced disease progression after autologous HCT, including 5 of the 6 patients (83%) with no inhibitory KIR-HLA mismatch and 3 of the 6 patients (50%) with 1 mismatched pair; none of the 4 (0%) patients with 2 mismatched pairs experienced disease progression. Survival analyses showed that inhibitory KIR-HLA mismatch was the only significant prognostic factor (P=0.01). The potential applicability of the receptor-ligand mismatch model to autologous HCTs and to patients with lymphoma or solid tumour is clinically significant because of the prevalence of the HCT procedure.
Leung
W
W
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. wing.leung@stjude.org
Handgretinger
R
R
Iyengar
R
R
Turner
V
V
Holladay
M S
MS
Hale
G A
GA
D015331:Cohort Studies; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D020350:Graft vs Tumor Effect / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D020014:K562 Cells; D008223:Lymphoma / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009369:Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D012008:Recurrence; D014181:Transplantation Immunology; D014182:Transplantation, Autologous
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D054340:Receptors, KIR