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Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants

T cells that accompany allogeneic hematopoietic grafts for treating leukemia enhance engraftment and mediate the graft-versus-leukemia effect. Unfortunately, alloreactive T cells also cause graft-versus-host disease (GVHD). T cell depletion prevents GVHD but increases the risk of graft rejection and...

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Published in:Science (American Association for the Advancement of Science) 2002-03, Vol.295 (5562), p.2097-2100
Main Authors: Ruggeri, Loredana, Capanni, Marusca, Urbani, Elena, Perruccio, Katia, Shlomchik, Warren D., Tosti, Antonella, Posati, Sabrina, Rogaia, Daniela, Frassoni, Francesco, Aversa, Franco, Martelli, Massimo F., Velardi, Andrea
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Language:English
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Summary:T cells that accompany allogeneic hematopoietic grafts for treating leukemia enhance engraftment and mediate the graft-versus-leukemia effect. Unfortunately, alloreactive T cells also cause graft-versus-host disease (GVHD). T cell depletion prevents GVHD but increases the risk of graft rejection and leukemic relapse. In human transplants, we show that donor-versus-recipient natural killer (NK)-cell alloreactivity could eliminate leukemia relapse and graft rejection and protect patients against GVHD. In mice, the pretransplant infusion of alloreactive NK cells obviated the need for high-intensity conditioning and reduced GVHD. NK cell alloreactivity may thus provide a powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1068440