14thInternational HLA and Immunogenetics Workshop: report on hematopoietic cell transplantation.

Deciphering the role of human leukocyte antigen (HLA), killer immunoglobulin like receptor, and immune response genes in a model as complex as unrelated donor hematopoietic cell transplantation is a challenge. The allelic diversity of these genes is shaped by the race and ethnicity of transplant donors and recipients. Coupled with the genetic polymorphism is the complexity of clinical phenotypes of transplant populations: donor and recipient demographic characteristics and the regimens used by transplant physicians to prepare patients for transplantation and to prevent and treat graft-vs-host disease (GVHD). Furthermore, GVHD is itself a complex disease shaped by both genes and 'environment'. How does one begin to deconstruct the genetic barrier to understand risk factors important to transplant outcome? To begin with, population-based studies, particularly retrospective ones, benefit from adequate sample sizes to measure genetic effects. The more homogeneous the population for variables that influence clinical endpoints, the higher the likelihood that a real genetic effect can be uncovered. Even so, the feasibility of studies can be hampered if genotype and clinical data are not both complete and precise. For studies of HLA, diversity of alleles and antigens contributed by ethnically different transplant populations is an asset, because not only can a broader range of HLA mismatches be studied but they provide the opportunity for side-by-side analyses that may yield clues as to why transplant outcomes differ between populations.