当前位置： SCI文献检索 > CLINICAL AND EXPERIMENTAL IMMUNOLOGY期刊下所有文献 > Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation.

Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation.

Abstract：

:To define the role of quantitative graft composition and donor killer-cell immunoglobulin-like receptor (KIR) genotype in clinical outcome following unmanipulated peripheral blood stem cell transplantation (PBSCT) from human leucocyte antigen (HLA)-identical siblings, 43 consecutive transplants for haematological malignancies were analysed retrospectively. Twenty-four patients underwent myeloablative conditioning and 19 received busulphan/fludarabine-based reduced intensity conditioning (RIC). In patients with acute myelogenous leukaemia or myelodysplastic syndrome (AML/MDS; n = 18), no relapse occurred following transplants meeting both a high (above median) natural killer (NK) cell count and missing HLA-ligand(s) to donor's KIR(s), compared to all other AML/MDS patients (0% versus 44%; P = 0.049). Missing HLA-B and/or HLA-C ligand combined with missing HLA-A3/11 (KIR3DL2 unblocked) predicted for reduced relapse incidence regardless of diagnosis or conditioning type (P = 0.028). Moreover, in AML/MDS patients, this constellation predicted superior overall survival (OS) (P = 0.046). Transplants with more than two different activating donor KIRs were associated with an increased risk for non-relapse mortality (NRM), both by univariate and multivariate analysis. Quantitative graft composition had a significant impact exclusively in RIC transplants. Here, a trend towards reduced relapse incidence was found in patients receiving high numbers of NK cells (16% versus 54%; P = 0.09). In patients receiving high versus low T cell numbers, OS was superior (83% versus 37%; P = 0.01), due mainly to reduced NRM (0% versus 33%; P = 0.046). By multivariate analysis, relapse risk was decreased significantly in patients receiving high NK cell numbers (P = 0.039). These data suggest that both the number of transplanted NK cells and the donor KIR genotype play a role in graft-versus-malignancy mechanisms in HLA-identical PBSCT.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Clausen J,Wolf D,Petzer AL,Gunsilius E,Schumacher P,Kircher B,Gastl G,Nachbaur D

doi

10.1111/j.1365-2249.2007.03360.x

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

520-8

issue

3

eissn

0009-9104

issn

1365-2249

pii

CEI3360

journal_volume

148

pub_type

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