Key Points MICA-129 matching improves survival in uHSCT. MICA-129 mismatches were observed in 6.7% of all transplant patients.

Unrelated hematopoietic stem cell transplantation (HSCT) has evolved from an experimental protocol to a potentially curative first-line treatment in certain disease instances. Factors enabling this transformation were the optimization of treatment protocols and supportive care as well as the availability of a large number of donors worldwide along with the higher quality and reliability of HLA typing. The main criterion for donor selection is HLA compatibility. In this review we discuss the current clinical evidence of HLA matching in unrelated HSCT. In this context, we address methodical aspects of transplantation immunobiology research and discuss the impact of locus and resolution of HLA differences. Furthermore, we address special constellations such as unidirectional mismatches or the presence of nonexpressed alleles as well as HLA alloimmunization and describe the perspective for HLA typing and matching strategies in the future, given the implementation of novel complete or near-complete gene typing approaches using next-generation sequencing short read technology, which are now entering the standard of clinical care.