title: Antibody desensitization therapy in highly sensitized lung transplant candidates.
abstract: As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multi-modal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000-10,000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: L D
authors.initials: LD
authors.lastname: Snyder
authors.forename: A L
authors.initials: AL
authors.lastname: Gray
authors.forename: J M
authors.initials: JM
authors.lastname: Reynolds
authors.forename: G M
authors.initials: GM
authors.lastname: Arepally
authors.forename: A
authors.initials: A
authors.lastname: Bedoya
authors.forename: M G
authors.initials: MG
authors.lastname: Hartwig
authors.forename: R D
authors.initials: RD
authors.lastname: Davis
authors.forename: K E
authors.initials: KE
authors.lastname: Lopes
authors.forename: W E
authors.initials: WE
authors.lastname: Wegner
authors.forename: D F
authors.initials: DF
authors.lastname: Chen
authors.forename: S M
authors.initials: SM
authors.lastname: Palmer
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003888:Desensitization, Immunologic; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology*; D008171:Lung Diseases / Q000401:mortality / Q000601:surgery*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies
keywords: Desensitization; HLA; highly sensitized; lung; pretransplant