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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2003-01-0091. This Article Full Text (PDF) All Versions of this Article: 2003-01-0091v1 102/3/814    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Giebel, S. Articles by Holowiecki, J. Search for Related Content PubMed PubMed Citation Articles by Giebel, S. Articles by Holowiecki, J. Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted January 14, 2003 Accepted March 25, 2003 Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors Sebastian Giebel, Franco W Locatelli*, Teresa Lamparelli, Andrea Velardi, Stella M Davies, Guido Frumento, Rita Maccario, Federico Bonetti, Jerzy Wojnar, Miryam Martinetti, Francesco Frassoni, Giovanna Giorgiani, Andrea Bacigalupo, and Jerzy Holowiecki Department of Haematology and BMT, Silesian Medical Academy, Katowice, Poland Oncoematologia Pediatrica, IRCCS Policlinico San Matteo, Pavia, Italy Divisione di Ematologia II, Ospedale San Martino, Genova, Italy Department of Clinical and Experimental Medicine, Division of Hematology and Clinical Immunology, University of Perugia, Perugia, Italy Blood and Marrow Transplant Program, Univertity of Minnesota, Minneapolis, MN, USA Laboratorio di Immunogenetica, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Servizio di Immunologia e Trasfusione, Centro di Immunologia dei Trapianti, IRCCS Policlinico San Matteo, Pavia, Italy * Corresponding author; email: f.locatelli{at}smatteo.pv.it. Killer immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction was previously demonstrated to be associated with improved outcome in patients given haploidentical, T-cell depleted transplants of hematopoietic stem cells (HSCT). The goal of this study was to evaluate whether that observation could be generalized for patients receiving unmanipulated HSCT from unrelated donors (URD). One hundred and thirty patients with hematological malignancies entered the study. GVHD prophylaxis was uniform and consisted of cyclosporin, short-term methotrexate and pre-transplant anti-thymocyte globulin (ATG). Patients were divided into those with (n=20) and those without (n=110) KIR ligand incompatibility with respect to their donors. At 4.5 years patients with KIR ligand incompatibility had higher probability of overall survival (87% vs. 48%, p=0.006) and disease-free survival (87% vs. 39%, p=0.0007) compared with those without KIR ligand incompatibility. Transplant-related mortality for the two groups equaled 6% and 40% (p=0.01), respectively. Relapse rates for patients transplanted from a donor with or without KIR ligand incompatibility were 6% and 21%, respectively (p=0.07). All patients with myeloid malignancies who had a KIR ligand disparate donor (n=13) are alive and disease-free. The incidence of grade III-IV acute GVHD and GVHD-related mortality was reduced in the KIR ligand mismatched group (0% vs. 15%, p=0.08 and 6% vs. 29%, p=0.09, respectively). These data indicate that NK cell alloreactivity is associated with better outcome after URD-HSCT when ATG is used as part of GVHD prophylaxis. This may result from both a more favorable graft-versus-malignancy effect and a lower risk of developing severe GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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