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Blood, 1 July 2007, Vol. 110, No. 1, pp. 433-440.
Prepublished online as a Blood First Edition Paper on March 19, 2007; DOI 10.1182/blood-2006-07-038687.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value.
Loredana Ruggeri1,
Antonella Mancusi1,
Marusca Capanni1,
Elena Urbani1,
Alessandra Carotti1,
Teresa Aloisi1,
Martin Stern1,
Daniela Pende2,
Katia Perruccio1,
Emanuela Burchielli1,
Fabiana Topini1,
Erika Bianchi1,
Franco Aversa1,
Massimo F. Martelli1, and
Andrea Velardi1
1 Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation on Transplantation Biotechnologies, Perugia, Italy; and
2 Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
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.
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