Myeloid and lymphoid malignancies are potentially curable through a graft versus leukaemia (GvL) effect following allogeneic haematopoietic stem cell transplantation. Whilst donor T cell are thought to be the main mediators of GvL, the effect of donor NK cells within HLA matched T cell depleted transplant setting is more unclear. Patient blood samples were analysed during the first month post-transplant, with higher reconstitution of NK cells at two weeks conferring a relapse protection association. Donor stem cell graft samples, from which NK cells within the patient at two weeks are thought to be derived, similarly displayed a strong association between high NK cell dose and protection from disease relapse. CD56dimDNAM+ NK cells were found to be the population with the most significant association. The ability of NK cells to kill AML blasts in a DNAM dependent manner was shown indicating that direct killing of residual tumour cells may be a valid mechanism of GvL. These findings suggest that optimising the number of NK cells within stem cell grafts should be considered as a means to prevent disease relapse.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:760495 |
| Date | January 2018 |
| Creators | Maggs, Luke |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/8633/ |
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