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Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation |
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| Authors: | Christopher R. Ensor Lindsey C. Rihtarchik Matthew R. Morrell J. W. Awori Hayanga Alicia B. Lichvar Joseph M. Pilewski Stephen Wisniewski Bruce A. Johnson Jonathan D'Cunha Adriana Zeevi John F. McDyer |
| Affiliation: | 1. Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA;2. Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;3. The Ohio State University Wexner Medical Center, Columbus, OH, USA;4. Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;5. Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA;6. Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA;7. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA |
| 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. |
| Keywords: | acute cellular rejection alemtuzumab bronchiolitis obliterans syndrome lung transplant rescue |