How to select a donor and hematopoietic stem cell source: Related versus unrelated donors for allogeneic HSCT

The selection of the most suitable donor and stem cell source is a critical component of hematopoietic stem cell transplantation (HSCT). The factors that contribute to this selection are many, making the process complex. The most important contributing factor of donor selection and stem source is based on the inherent genetic makeup of the donor as it relates to the HSCT recipient. The cluster of genes that compared for compatibility (termed histocompatibility) contain human leukocyte antigens (HLA) genes located in the short arm of chromosome 6 in humans. These genes are inherited together (i.e., linked), and the most important determinants are HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1. Because a person inherits one HLA cluster (termed locus) from each parent, siblings with the same parents have a 25% chance to be a “match” with the potential HSCT recipient. The process of evaluating histocompatibility is termed HLA matching and can be performed at the antigen and allele level. The allele level is more accurate and thus is termed “high-resolution” typing. Because increased HLA disparity between the donor and recipient increases post-HSCT morbidity and mortality, every effort is made to select the most suitable donor in terms of HLA histocompatibility. Potential hematopoietic stem cell (HSC) sources include bone marrow, peripheral blood after cytokine mobilization, and umbilical cord blood. Each HSC source is commonly used, with bone marrow as the most common source for pediatric allogeneic HSCT. However, umbilical cord blood is used frequently as an alternative source when no suitable related or unrelated matched sibling donor is available. Because of the nature of the naïve T cells contained within umbilical cord blood, greater HLA disparity between umbilical cord blood donor source and the potential HSCT recipient is better tolerated than with bone marrow or peripheral blood HSCs. Haploidentical related donors as HSC source is being used more frequently but is still considered investigational in the pediatric population.