Donor HLA-specific Abs: to BMT or not to BMT?

The engraftment failure associated with Abs to donor-specific HLA (DSA) limits options for sensitized BMT candidates. Fourteen of fifteen patients with no other viable donor options were desensitized and transplanted using a regimen of plasmapheresis and low-dose i.v. Ig modified to accommodate pre-BMT conditioning. DSA levels were assessed by solid-phase immunoassays and cell-based crossmatch tests. DSA levels were monitored throughout desensitization and on day - 1 to determine if there was any DSA rebound that would require additional treatment. A mean reduction in DSA level of 64.4% was achieved at the end of desensitization, with a subsequent reduction of 85.5% after transplantation. DSA in 11 patients was reduced to levels considered negative post-BMT, whereas DSA in three patients remained at low levels. All 14 patients achieved donor engraftment by day +60; however, seven patients suffered disease relapses. Four patients experienced mild, grade 1 GVHD. Factors influencing the response to desensitization include initial DSA strength, number, specificity, DSA rebound and a mismatch repeated from a prior transplant. While desensitization should be reserved for patients with limited donor options, careful DSA assessment and monitoring can facilitate successful engraftment after BMT.