Incidence of humoral sensitization in HLA partially mismatched hematopoietic stem cell transplantation

As part of the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), seven centers participated in a collaborative project to determine whether any significant humoral sensitization occurred post‐transplant among recipients of HLA partially mismatched hematopoietic cell transplants (HCTs). A total of 140 donor/recipient pairs were enrolled with a total of 367 pre‐and post‐transplant sera analyzed. The majority of the samples (69.1%) were obtained within 30–90 days post‐HCT. HLA‐specific antibodies were defined using single antigen bead assays on a Luminex™ platform with a positive cutoff value of 1000 normalized median fluorescence intensity (MFI). There was an overall incidence of post‐HCT sensitization toward donor HLA mismatches of 5.7%; however, all cases were among recipients of one HLA haplotype‐mismatched grafts under nonmyeloablative, pre‐transplant conditioning. Among the one haplotype‐mismatched recipients, 15.7% (8/51) developed donor HLA‐specific antibodies and 29.4% also had antibodies directed toward third party HLA antigens. Among the donor‐specific antibodies, 9.8% were directed toward HLA class I antigens; 7.8% were against class II antigens; and 2.0% had both class I and II specificity. The relative strength of post‐transplant antibodies was low with no significant difference in the mean maximum MFI values between third party and donor‐specific antibodies. Because only a small number (10.2%) of the post‐transplant samples were obtained 180 days or more post‐HCT, longer term study is needed to evaluate any clinical relevance of these low‐to‐moderate levels of donor‐specific antibody in one haplotype‐mismatched recipients, as well as to determine whether any other antibodies occur at later times.