PB1984 OUTCOMES WITH EXTRACORPOREAL PHOTOPHERESIS IN THE MANAGEMENT OF CHRONIC LUNG ALLOGRAFT DYSFUNCTION: A SINGLE-CENTRE EXPERIENCE

Abstract

Background: Chronic lung allograft dysfunction (CLAD) develops in 50% of patients 5 years post lung transplant and is a major cause of morbidity and mortality (approx. 30% 3-year mortality). Unfortunately, there are very few therapies that favourably change the natural history of CLAD once established. Extracorporeal Photopheresis (ECP) has previously been studied in acute rejection of cardiac and lung allograft patients with promising results (Snyder LD et al. Chest; 2013). Here we report our single-centre experience of 13 lung transplant patients with CLAD who underwent treatment with ECP. Aims: To identify if patients with CLAD and have an improvement or stabilisation of lung function with ECP. Methods: A retrospective case note audit identified 13 lung transplant recipients who commenced ECP for CLAD between 2013 and 2018 at The Peter MacCallum Cancer Centre and Alfred Hospital. CLAD was defined as a persistent decrease in Forced Expiratory Volume in 1 second (FEV1) and/or Forced Vital Capacity (FVC) of at least 20% compared to baseline values (mean of the two best post-operative values at least 3 weeks apart. Results: Median age when starting ECP was 54 years (range 25-73). 62% patients were male (n = 8) and 38% Female (n = 5). Reasons for lung transplant included Cystic Fibrosis (n = 4; 30%), Chronic Obstructive Pulmonary Disease (n = 4; 30%), Pulmonary Hypertension (n = 1; 8%), Non-specific Interstitial Lung Disease (n = 1; 8%), Idiopathic Pulmonary Fibrosis (n = 1; 8%) and re-transplants for CLAD (n = 2; 16%). Underlying subtypes of CLAD included Bronchiolitis Obliterans Syndrome (BOS: n = 5; 38%), Restrictive Allograft Syndrome (RAS: n = 2; 16%), BOS/RAS (n = 5; 38%) and no rejection (n = 1; 8%). The patient who had no rejection was started on ECP to stop other immunosuppression due to multiple life threatening infections. Patients had previously received immunosuppression with Prednisolone (n = 13; 100%), Tacrolimus (n = 13; 100%), Azathioprine (n = 3; 25%), Mycophenolate (n = 7; 58%) or neither agent (n = 2; 17%). 1 patient was CLAD Stage 0 (8%), 2 patients CLAD Stage 2 (15%) and 10 patients CLAD Stage 3 (77%). Median White Cell Count (WCC) was 5.52, median Ne count 3.7x109 and median Lymphocyte count 0.69x109. 8 patients (62%) were still receiving ECP, 3 had died/palliated (23%) and 2 were re-transplanted (15%). Donor specific antigens (DSA) were present in 38% (n = 5). Pre-ECP commencement, the median rate of lung function decline was 7.03mls/day compared to 1.48 ml/day post ECP treatment. Unfortunately, 4 patients lung function continued to decline despite ECP (31%), but 7 stabilised (54%) and 1 patients lung function improved (8%). Median duration of declining lung function before commencing ECP was 308 days (range 121 to 443 days). Interestingly of the patients not responding, all were leukopenic (Median = 2.49x109) with a reduction in neutrophil numbers (Median = 1.57x109). Once declining lung function was detected, patients did better when they started ECP treatment earlier in this cohort. Summary/Conclusion: ECP is an effective second line treatment for CLAD patients who have not responded to conventional immunosuppressive regimes. Patients with a normal white cell count and in whom ECP is instigated early in the CLAD process appear to respond better and this is consistent with the theory behind ECP. Therefore, ECP should be considered early in the treatment algorithm for CLAD and we aim to investigate this further though a Phase II clinical trial.