title: Donor HLA-specific Abs: to BMT or not to BMT?
abstract: 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.
authors.affiliation: Immunogenetics Laboratory, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Leffell
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, MD, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, MD, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Gladstone
mesh_terms: D064591:Allografts; D016026:Bone Marrow Transplantation; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies