title: Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation.
abstract: Despite substantial improvements in early survival after lung transplantation, refractory acute rejection (RAR) and bronchiolitis obliterans syndrome (BOS) remain major contributors to transplant-related morbidity and mortality. We have utilized alemtuzumab, a humanized anti-CD52 antibody which results in potent lymphocyte depletion, in consecutive patients with RAR (n = 12) or BOS (n = 10). All patients failed conventional treatment with methylprednisolone and antithymocyte globulin and received strict infection prophylaxis. Alemtuzumab significantly improved histological rejection scores in RAR. Total rejection grade/biopsy was 1.98 +/- 0.25 preceding alemtuzumab versus 0.33 +/- 0.14 posttreatment, p-value <0.0001 (with a similar number of biopsies/patient per respective time interval). Freedom from BOS was observed in 65% of RAR patients 2 years after alemtuzumab treatment. Although there was no statistically significant change in forced expiratory volume in 1 second (FEV1) before and after alemtuzumab treatment in patients with BOS, a stabilization or improvement in BOS grade occurred in 70% of patients. Patient survival 2 years after alemtuzumab for BOS was 69%. Despite a dramatic decline in CD4 counts in alemtuzumab-treated patients, only one patient developed a lethal infection. Thus, we provide the first evidence that alemtuzumab is a potentially useful therapy in lung transplant recipients with RAR or BOS.
authors.affiliation: Department of Pharmacy, Duke University Medical Center, Durham, NC, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Reams
authors.forename: L W
authors.initials: LW
authors.lastname: Musselwhite
authors.forename: D W
authors.initials: DW
authors.lastname: Zaas
authors.forename: M P
authors.initials: MP
authors.lastname: Steele
authors.forename: S
authors.initials: S
authors.lastname: Garantziotis
authors.forename: P C
authors.initials: PC
authors.lastname: Eu
authors.forename: L D
authors.initials: LD
authors.lastname: Snyder
authors.forename: J
authors.initials: J
authors.lastname: Curl
authors.forename: S S
authors.initials: SS
authors.lastname: Lin
authors.forename: R D
authors.initials: RD
authors.lastname: Davis
authors.forename: S M
authors.initials: SM
authors.lastname: Palmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D000074301:CD52 Antigen; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006023:Glycoproteins / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab