Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders
C Chen,Marc Busson,V. Rocha,M-L Appert,Virginia Lepage,Nicolas Dulphy,Philippe Haas,Gérard Socié,Antoine Toubert,Dominique Charron,Pascale Loiseau +10 more
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TLDR
The impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT is highlighted.Abstract:
Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and are still unknown for activating KIR. The impact of activating KIR genotypes from donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft-versus-host disease (GVHD), relapse, survival or infections even in myeloid malignancies. However, additional activating KIR genes in the donor compared to the recipient's genotype or an identity between donor and recipient activating KIR genotypes was associated with a lower transplant-related mortality (TRM) (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28; P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.read more
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Targeting natural killer cells and natural killer T cells in cancer.
TL;DR: The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.
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Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia
Sarah Cooley,Daniel J. Weisdorf,Lisbeth A. Guethlein,John P. Klein,Tao Wang,Chap T. Le,Steven G.E. Marsh,Daniel E. Geraghty,Stephen R. Spellman,Michael Haagenson,Martha Ladner,Elizabeth Trachtenberg,Peter Parham,Jeffrey S. Miller +13 more
TL;DR: KIR genotyping of several best HLA-matched potential unrelated donors should substantially increase the frequency of transplants by using grafts with favorable KIR gene content, which could result in superior disease-free survival for patients with AML.
Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia
Sarah Cooley,Daniel J. Weisdorf,LA Guethlein,John P. Klein,Tao Wang,Chap T. Le,Sge Marsh,Daniel E. Geraghty,S Spellman,Haagenson,Martha Ladner,Elizabeth Trachtenberg,Peter Parham,Jeffrey S. Miller +13 more
TL;DR: In this article, the authors compared the contribution of centromeric and telomeric motifs to the clinical benefit of B haplotype donors for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL).
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How we treat cytomegalovirus in hematopoietic cell transplant recipients
Michael Boeckh,Per Ljungman +1 more
TL;DR: Various aspects of CMV treatment and prevention in HCT recipients are reviewed, including currently used drugs and diagnostics, ways to optimize preemptive therapy strategies with quantitative polymerase chain reaction assays, the use of prophylaxis, management ofCMV disease caused by wild-type or drug-resistant strains, and future strategies.
Journal ArticleDOI
Differential natural killer cell–mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes
Galit Alter,Maureen P. Martin,Nickolas Teigen,William H. Carr,Todd J. Suscovich,Arne Schneidewind,Hendrik Streeck,Michael S Waring,Angela Meier,Christian Brander,Jeffrey D. Lifson,Todd M. Allen,Mary Carrington,Marcus Altfeld +13 more
TL;DR: The functional ability of NK cells to differentially control HIV-1 replication in vitro based on their KIR and HLA types is examined, providing the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication.
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Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS
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