Tuesday, January 29, 2013

Partially Mismatched Transplantation and HLA Donor Specific Antibodies.

The presence of donor HLA-specific antibodies (DSA) increases engraftment failure risk in partially-HLA mismatched, or HLA-haploidentical, allogeneic marrow (alloBMT) transplantation. As pre-existing sensitization to HLA antigens is not well characterized among candidates for HLA-haploidentical alloBMT, we retrospectively evaluated both the incidence and relative strength of DSA in this patient population. Based on correlations of solid phase antibody assays on the Luminex™ platform with actual crossmatch tests, DSA were characterized as weak for results that were consistent with negative flow cytometric crossmatch results or as moderate to strong for results consistent with positive flow cytometric or cytotoxicity crossmatches. 296 alloBMT candidates (111 [37.5%] female) were evaluated. DSA were detected in 43 (14.5%) candidates, mostly among female candidates (42.9% female vs. 12.5% male). Moderate to strong DSA strength was more frequently encountered when directed against haploidentical donors as compared to mismatched unrelated donors. DSA were most commonly detected in female patients directed against their children. Because the presence of DSA has been considered prohibitive for HLA mismatched alloBMT, we additionally report a desensitization methodology used to reduce DSA to negative or weak levels. i.e., levels well below those detectable in a flow cytometric crossmatch. Nine patients without other available donors underwent desensitization. Eight reduced their DSA to negative or weak levels proceeded to alloBMT and achieved full donor engraftment. These data support routine DSA evaluation in all patients considered for mismatched alloBMT; however, for patients with no other viable options, desensitization to weak or negative DSA levels may afford the opportunity for successful transplantation (read more) Print this post

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