title: Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation.
abstract: Refractory acute cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post-lung transplantation. We report the largest cohort of lung transplant recipients (LTRs) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30 days before and 180 days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0-6) and freedom from ≥A2 ACR. BOS outcomes included freedom from BOS progression and FEV1 decline >10%. Univariate parametric and nonparametric statistical approaches were used to assess treatment response. Kaplan-Meier method with log rank conversion was used to assess freedom from events. Fifty-seven alemtuzumab doses (ACR 40 and BOS 17) given to 51 patients were included. Median time to rescue was 722 (IQR 42-1403) days. CRSS declined significantly (3 vs 0.67, P<0.001) after rescue. Freedom from ≥A2 was 62.5% in rACR. Freedom from BOS progression was 52.9% at 180 days in the BOS cohort. Freedom from FEV1 decline >10% was 70% in BOS grade 1 and 14.3% in advanced BOS grades 2-3. Infections developed in 72.5% and 76.5% of rACR and BOS groups. Rescue alemtuzumab appears useful for rACR. Patients with BOS 1 may have transient benefit, and patients with advanced BOS seem not to respond to alemtuzumab.
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.|Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Christopher R
authors.identifier: 0000-0003-0990-1406
authors.initials: CR
authors.lastname: Ensor
authors.affiliation: The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Lindsey C
authors.initials: LC
authors.lastname: Rihtarchik
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Morrell
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: J W Awori
authors.initials: JW
authors.lastname: Hayanga
authors.affiliation: Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA.
authors.forename: Alicia B
authors.initials: AB
authors.lastname: Lichvar
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wisniewski
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Johnson
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'Cunha
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: McDyer
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000074323:Alemtuzumab
keywords: acute cellular rejection; alemtuzumab; bronchiolitis obliterans syndrome; lung transplant; rescue