A Case Series Describing Response to Rabbit Anti-thymocyte Globulin for the Treatment of Bronchiolitis Obliterans Syndrome in Patients With Chronic Lung Allograft Dysfunction
Recommended Citation
Fitzmaurice M, Franco-Palacios DJ, Henderson R, Olexsey K, Pinto Corrales J, Poparad-Stezar A, Stagner LD, Allenspach L. A Case Series Describing Response to Rabbit Anti-thymocyte Globulin for the Treatment of Bronchiolitis Obliterans Syndrome in Patients With Chronic Lung Allograft Dysfunction. Am J Respir Crit Care Med 2024; 209:A3733.
Document Type
Conference Proceeding
Publication Date
6-1-2024
Publication Title
Am J Respir Crit Care Med
Keywords
azithromycin, calcineurin, thymocyte antibody, adult, allograft, bronchiolitis obliterans, bronchiolitis obliterans syndrome, case study, clinical article, complication, conference abstract, controlled study, cystic fibrosis, drug dose reduction, drug therapy, female, follow up, forced expiratory volume, human, immunosuppressive treatment, Leporidae, lung fibrosis, male, median survival time, middle aged, oxygen therapy, phase 2 clinical trial, retrospective study, salvage therapy, sarcoidosis, serum sickness, side effect, special situation for pharmacovigilance, spirometry, therapy, treatment response
Abstract
Background: Chronic allograft dysfunction (CLAD) is a frequent complication and main reason for morbidity and decreased survival after lung transplant. Besides augmented immunosuppression and azithromycin, few other salvage therapies exist. Anti-thymocyte globulin therapy (ATG) is commonly offered to patients. The goal is to attenuate the rate of disease progression, stabilize or improve forced expiratory volume in 1 second (FEV1). Few centers have reported their treatment response with thymoglobulin and with varying doses. Methods: We reviewed all patients treated at our center with ATG for CLAD from 2015 to 2023. Their treatment response and side effects are described in 16 patients (BOS in 14, BOS + RAS in 2). Results: Median age 61, 81% were men, 15 patients underwent bilateral lung transplant. Most common indication was pulmonary fibrosis (6/16, 37%), followed by emphysema, cystic fibrosis and sarcoidosis. All patients received standard induction. Triple maintenance immunosuppression with calcineurin and cell cycle inhibitors and steroids were used in 68% of patients. Most patients (14/16, 87%) were taking azithromycin 250 mg three times weekly. The median cumulative ATG dose was 2.25 mg/kg with a median of 2 doses per course. Median time from transplant to BOS development was 24 months. Most patients (80%) had BOS stages 3 (9/16; 56%) and 4 (3/16, 18%). The median rate of FEV1 decline was - 142 mL/month. Eight patients had follow-up spirometry at 6 months post ATG. All eight (8/16, 50%) had attenuated decline or improvement in FEV1 in 4 and 4 patients, respectively. Four patients with shorter follow-up post ATG (2 to 4.5 months) have also responded to ATG (1 unchanged, 2 improved and 1 attenuated decline in FEV1). At the time of data censoring, responders had a median survival of 11 months. Baseline FEV1 was lower in non-responders. Five of them declined rapidly and died. Serum sickness was diagnosed in one patient post ATG. Three patients required dose reductions or slower infusion rate due to tolerability. Conclusions: Attenuated decline, stabilization, or improvement in FEV1 was seen in 68% (11/16) of patients at any time post ATG. Four patients with early BOS (stages 1 and 2) had improved FEV1 after ATG. Even in patients with late CLAD (BOS s-3 and 4, or on chronic oxygen therapy) ATG was of some benefit (partial response in 6/12, 50%). Our outcomes are consistent with previous reports and suggest that ATG at lower cumulative doses could benefit patients with CLAD.
Volume
209
First Page
A3733
