A strategy to reduce donor-specific HLA Abs before allogeneic transplantation

摘要

Donor-specific anti-HLA Abs (DSA) are implicated in graft failure after Allo-SCT. In our program, high-resolution typing for HLA-A, -B, -C, -DRB1, -DQ and -DP loci is therefore routinely performed for all recipients and stem cell donors, though some umbilical cord blood (UCB) units lack DQ or DP typing. In addition, serum samples of the recipient are tested for IgG Abs against HLA class I and class II Ags by a solid phase immunoassay (Luminex Corporation, Austin, TX, USA). We attempt to avoid graft sources that have HLA Ags or alleles targeted by these Abs. But in some cases all potential related or unrelated grafts are targeted by DSA at levels of >1000 mean florescence intensity (MFI) to one or more of the mismatched HLA alleles. For such cases we developed a strategy to decrease the DSA burden before SCT.Desensitization started 4-6 weeks before transplant and involved bortezomib 1.3mg/m2 on days 1, 4, 8 and 11, rituximab 375mg/m2 weekly, i.v. Ig lOOOmg/kg, plasmapheresis (in which one plasma volume was exchanged with a 5% albumin replacement solution twice weekly), or in most cases combinations of these interventions. Plasmapheresis was continued after stem cell infusion until neutrophil engraftment in three patients with persistently high DSA levels (patients 2, 5 and 10). DSA levels were tested at baseline and at weekly intervals from the time of starting the DSA reductive therapy until engraftment.