Clinical Oncology and Molecular Diagnostics

Allogeneic hematopoietic stem cell recipients may have performed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. Recently developed technology using solid phase immunoassays (SPIs) with fluorochromeconjugated beads has greatly improved the ability to detect and classify DSAs. When used in combination with the classic lymphocytotoxic complement-dependent and flow cytometric cross match tests, SPIs help provide DSA strength assessment. Both CD34+ cells and T-cells are required for donor engraftment; however, the expression of HLA antibodies varies between these cells: all HLA loci are expressed on CD34+ cells (HLA-A highest, HLA- DQ lowest); HLA-A and B expression is higher on CD34+ cells than on T cells; HLA-C expression is lower on CD34+ than on T cells. Parous females frequently harbor DSAs. DSAs tend to be of higher intensity when directed against haploidentical first-degree relatives. DSA assessment requires frequent monitoring as their relative strength can change over time. Importantly, patients who harbor flow cytometric cross match detectable DSA who are treated with a combination of plasma exchange with intravenous immune immunoglobulin, tacrolimus and mycophenolate mofetil can often lower DSA levels to well below flow cross match detection. Although the criteria that constitutes a prohibitive DSA is unknown, desensitization can result in engraftment rates as experienced in fully HLA-matched allogeneic blood or marrow transplantation recipients.