Donor natural killer cell allorecognition of missing self in haploidentical hernatopoietic transplantation for acute myeloid leukemia: challenging its predictive value

被引:468
作者
Ruggeri, Loredana
Mancusi, Antonella
Capanni, Marusca
Urbani, Elena
Carotti, Aiessandra
Aloisi, Teresa
Stern, Martin
Pende, Daniela
Perruccio, Katia
Burchielli, Emanuela
Topini, Fabiana
Bianchi, Erika
Aversa, Franco
Martelli, Massimo F.
Velardi, Andrea
机构
[1] Univ Perugia, Policlin Monteluce, Dept Clin & Expt Med, Div Hematol & Clin Immunol,IRCCS,Fdn Transplantat, I-06122 Perugia, Italy
[2] Ist Nazl Ric Canc, I-16132 Genoa, Italy
关键词
D O I
10.1182/blood-2006-07-038687
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 1, 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% Cl, 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.
引用
收藏
页码:433 / 440
页数:8
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