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Allografting

Natural killer-cell KIR repertoire reconstitution after haploidentical SCT

Abstract

We studied killer-cell Ig-like receptor (KIR)/natural killer (NK)-cell group-2-Ag repertoires on donor-derived NK cells in 28 patients after haploidentical SCT in the first 6 months after SCT and correlated results with EFS. The reconstitution hierarchy of potentially alloreactive, single KIR+ NK cells was the following: HLA-C1 binding>HLA-Bw4 binding>HLA-C2 binding. The differences in reconstitution kinetics of the three potentially alloreactive NK cell subsets prompted an updated analysis of EFS in AML patients transplanted from haploidentical donors in our center. This analysis showed that in haploidentical transplantation for AML, HLA-C group 1 mismatching in the graft vs host direction not only provides a survival advantage over non-NK-alloreactive (KIR ligand-matched) transplants (5-year EFS 67±10% vs 17±5%) but, indeed, also provides the best EFS compared with C2 (35±10%) or Bw4 KIR ligand mismatches (44±17%). In conclusion, we show that the kinetics with which single KIR-expressing NK cells are generated after haploidentical SCT differ between individual KIR receptors and seem to influence survival after haploidentical SCT.

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Acknowledgements

This study was supported by grants from the Italian Association for Cancer Research, the Leukemia and Lymphoma Society, the Italian Ministry of Further Education and the Italian Ministry of Health. LR is a Leukemia and Lymphoma Society Special Fellow in Clinical Research. AM is supported by fellowship from the Italian Foundation for Cancer Research. MS is supported by research grants from the Swiss Cancer League (Grant no. BIL OCS 01597–08–2004) and the Swiss National Science Foundation (grant PBBSB-107328).

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Correspondence to M Stern.

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Stern, M., de Angelis, C., Urbani, E. et al. Natural killer-cell KIR repertoire reconstitution after haploidentical SCT. Bone Marrow Transplant 45, 1607–1610 (2010). https://doi.org/10.1038/bmt.2010.19

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