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Effect of donor KIR Genotype on the outcome of bone marrow transplantation

Lee, Jia-Hui Jane (2013) Effect of donor KIR Genotype on the outcome of bone marrow transplantation. Honours thesis, Murdoch University.

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Haematopoietic stem cell transplantation is the only curative treatment for some forms of haematologcial malignancies and bone marrow failure. The role of donor Natural Killer (NK) cells that accompany the donor stem cells is under investigation. In particular, there is interest in the role of the killer immunoglobulin-like receptors (KIR) family of receptors expressed on the surface receptors of NK cells. In this study, we focused on the donor KIR genes and the possibility that the KIR receptors interact with other transplant variables to influence survival. We analyzed a cohort of 140 unrelated donors from bone marrow transplants carried out at Royal Perth Hospital and Princess Margaret Hospital. The variables that were analyzed for interactions with KIR were: cytomegalovirus (CMV) status, transplant graft source, conditioning agents. A number of significant interactions between KIR and transplant variables were identified, the strongest being the interaction between KIR2DS2 and the use of cyclophosphamide as a conditioning agent. Kaplan-Meier analyses showed that the presence of KIR2DS2 in a cyclophosphamide positive transplant resulted in a significantly improved survival (p=0.002) whereas the presence of KIR2DS2 in a cyclophosphamide negative transplant resulted in a poorer survival (p=0.032). Hence the presence of KIR2DS2 could be beneficial or deleterious depending on the presence or absence of cyclophosphamide. As this was an exploratory study, observations of the interactions discovered need to be confirmed in additional studies.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): School of Veterinary and Life Sciences
Supervisor(s): Green, Wayne, DeSantis, D. and Witt, C.S.
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