The studies described in this thesis are aimed at improving the whole spectrum of unrelated HSCT in order to help as many patients in need of HSCT as possible. It covers three different but related... Show moreThe studies described in this thesis are aimed at improving the whole spectrum of unrelated HSCT in order to help as many patients in need of HSCT as possible. It covers three different but related topics; from access to HSCT to optimizing donor search and selection of acceptable mismatches to improving HSCT outcome. In chapter 2 we investigate access to HSCT in the Netherlands for children with relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) to see whether patients eligible for HSCT are actually offered one and what might be the reasons for not referring a patient. Chapter 3 describes the role frequent HLA haplotypes may play in donor search and what the effect may be on HSCT outcome. In chapter 4 we propose an algorithm constructed by logistic regression analysis for prediction of CTL alloreactivity. It is based on number, position and physicochemical compatibility of AA differences in class I HLA molecules. This algorithm may be effective in identifying mismatched donors acceptable for HSCT. Before we can use this algorithm clinical validation is needed. Therefore we tried to translate the use of this algorithm from in vitro CTLp assay to in vivo HSCT. Studies aiming at the prediction of outcome of HSCT are described in chapter 5. Finally in chapter 6 we tested an algorithm developed by the transplantation group in Cambridge, which focused on electrostatic and hydrophobic properties of AA differences in class I HLA molecules, on the population we used for development of our own algorithm. Their algorithm was developed for prediction of humoral alloreactivity in organ transplantation and we wondered what could be the additional impact of a similar approach on cellular alloreactivity in HSCT. Show less
