On the role of HLA antibodies in hematopoietic stem cell transplantation

While the role of donor-specific antibodies (DSA) in solid organ transplantation is well established, their importance in hematopoietic stem cell transplantation (HSCT) is only now becoming clear. A review of the literature reporting on HLA immunization in HSCT provides ample circumstantial evidence that donor-specific HLA antibodies (DSA) are associated with a 2- to 10-fold increase of graft failure of HLA mismatched HSCT, irrespective the type of the graft, or the patient conditioning. Nevertheless, this is not a condition 'sine qua non', and engraftment has been documented despite the presence of DSA. However, prediction of graft failure based on serology is cumbersome. Although sensitivity and specificity of current solid-phase assays (SPAs) for HLA antibody detection are high, correlation with graft failure remains elusive. When lacking an alternative donor, reduction of strong reacting DSA must be attempted. Unfortunately, results of DSA reduction treatments in HSCT are scarcely reported. Case reports show that persisting DSA after plasma-exchange and immunosuppressive treatment can become negative after a 'last rescue' in vivo absorption with antigen-bearing platelets or donor lymphocyte transfusions. The destruction of engrafting hematopoietic cells by antibodies appears to be an immediate event. Blocking antibody mediated effector functions, e. g. with intravenous immunoglobulin (IvIg), may have additional value, despite IvIg often not reducing the antibody titre. An even less explored aspect of HLA-immunization is the presence of non-DSA antibodies in the host or HLA antibodies emerging post-transplantation. Such antibodies, either causally or as confounders, may be associated with negative transplant outcome. We conclude that HLA antibody assessment should be at the forefront in the treatment handbook of HSCT.