Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value.
We analyzed 112 patients with high-risk acute myeloid leukemia (61 in complete remission [CR]; 51 in relapse), who received human leukocyte-antigen (HLA)-haploidentical transplants from natural killer (NK) alloreactive (n = 51) or non-NK alloreactive donors (n = 61). NK alloreactive donors possessed HLA class I, killer-cell immunoglobulin-like receptor (KIR) ligand(s) which were missing in the recipients, KIR gene(s) for missing self recognition on recipient targets, and alloreactive NK clones against recipient targets. Transplantation from NK-alloreactive donors was associated with a significantly lower relapse rate in patients transplanted in CR (3% versus 47%) (P > .003), better event-free survival in patients transplanted in relapse (34% versus 6%, P = .04) and in remission (67% versus 18%, P = .02), and reduced risk of relapse or death (relative risk versus non-NK-alloreactive donor, 0.48; 95% CI, 0.29-0.78; P > .001). In all patients we tested the "missing ligand" model which pools KIR ligand mismatched transplants and KIR ligand-matched transplants from donors possessing KIR(s) for which neither donor nor recipient have HLA ligand(s). Only transplantation from NK-alloreactive donors is associated with a survival advantage.
Ruggeri
Loredana
L
Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Istituto di Ricovero e Cura a Carattere Scientifico, Foundation on Transplantation Biotechnologies, Perugia, Italy.
Mancusi
Antonella
A
Capanni
Marusca
M
Urbani
Elena
E
Carotti
Alessandra
A
Aloisi
Teresa
T
Stern
Martin
M
Pende
Daniela
D
Perruccio
Katia
K
Burchielli
Emanuela
E
Topini
Fabiana
F
Bianchi
Erika
E
Aversa
Franco
F
Martelli
Massimo F
MF
Velardi
Andrea
A
D000208:Acute Disease; D006239:Haplotypes; D006648:Histocompatibility; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007951:Leukemia, Myeloid / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D017634:Self Tolerance / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D011971:Receptors, Immunologic; D054340:Receptors, KIR