Human immunodeficiency virus and solid organ transplantation: a 15-year retrospective audit at a tertiary Australian transplant centre.

BACKGROUND: The incidence of end-stage organ disease in people living with human immunodeficiency virus (HIV) (PLWH) is increasing, as people live longer due to potent, tolerable antiretroviral therapy (ART). Consequently, the number of PLWH who would benefit from solid organ transplant (SOT) is rising. The SOT experience in PLWH in Australia remains limited. Aim To retrospectively review the outcomes for SOT in PLWH at our service, in Victoria, Australia. METHODS: A retrospective cohort study of PLWH undergoing SOT over a 15-year period was performed. Adult PLWH age >18 years were eligible and identified from the Victorian HIV Service database. Descriptive statistics were used to summarise baseline demographics and clinical data, and outcomes following SOT. RESULTS: Nine virologically suppressed PLWH underwent SOT from HIV-negative donors (five kidneys, two livers and two bilateral sequential lung transplants). All patients were male, with a median age of 57.3 years (interquartile range (IQR) = 54.3-60.1) and CD4 count of 485 (IQR = 342-835) at transplantation, and comorbidities were common at baseline. After a median follow up of 3.9 years (IQR = 2.7-7.6), 8 (89%) patents were alive, 7 (78%) had functioning grafts, although 5 (56%) experienced organ rejection. Infections were common. Two patients required modification to their ART due to significant drug-drug interactions prior to transplant, while 5 (56%) had modifications post-SOT. No patients experienced HIV virologic failure. CONCLUSION: PLWH with end-stage organ disease experience good clinical and functional outcomes and should be considered for SOT where indicated. However, multidisciplinary planning and care is essential to optimise care in this patient group.

Review: immunosuppression for the lung transplant patient.

Lung transplantation (LTx) has evolved significantly since its inception and the improvement in LTx outcomes over the last three decades has predominantly been driven by advances in immunosuppression management. Despite the lack of new classes of immunosuppression medications, immunosuppressive strategies have evolved significantly from a universal method to a more targeted approach, reflecting a greater understanding of the need for individualized therapy and careful consideration of all factors that are influenced by immunosuppression choice. This has become increasingly important as the demographics of lung transplant recipients have changed over time, with older and more medically complex candidates being accepted and undergoing LTx. Furthermore, improved survival post lung transplant has translated into more immunosuppression related comorbidities long-term, predominantly chronic kidney disease (CKD) and malignancy, which has required further nuanced management approaches. This review provides an update on current traditional lung transplant immunosuppression strategies, with modifications based on pre-existing recipient factors and comorbidities, peri-operative challenges and long term complications, balanced against the perpetual challenge of chronic lung allograft dysfunction (CLAD). As we continue to explore and understand the complexity of LTx immunology and the interplay of different factors, immunosuppression strategies will require ongoing critical evaluation and personalization in order to continue to improve lung transplant outcomes.

Favorable Outcome of Lung Transplantation for Severe Pulmonary Graft Versus Host Disease: An Australian Multicenter Case Series.

BACKGROUND: Severe pulmonary chronic graft versus host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation. Few treatments influence outcome, with 5-year overall survival as low as 13%. Lung transplantation (LTx) has been reported in small numbers of patients worldwide. METHODS: We investigated the outcomes of LTx performed for this indication at 2 large Australian LTx centers. RESULTS: Eighteen patients (aged 10-64 y; median, 29.6 y) received bilateral deceased lung transplants for pulmonary chronic GVHD between 2002 and 2017. LTx was performed at a median of 8.6 years after allogeneic stem cell transplantation (range, 2-23 y) with a median interval of 16 months from the time of transplant unit review to LTx. There were 2 early infective deaths and 3 further deaths from pulmonary infection and lung allograft rejection. There were no primary disease relapses. At a median follow-up of 5 years, the 5-year overall survival post-LTx is 80% and comparable to the Australia and New Zealand registry data of 64% for LTx performed for all indications. CONCLUSIONS: From one of the largest series of deceased LTx for this indication, we conclude that it is a feasible option for selected patients with severe pulmonary GVHD. The outcomes appear superior to that of non-LTx-based therapies and similar to the survival of the general LTx population. Establishing guidance on referral triggers, patient eligibility, organ selection, prophylaxis of allograft rejection, and supportive care would assist hematopoietic and lung transplant units in optimizing resource allocation and patient outcomes.

Domiciliary non-invasive ventilation post lung transplantation.

BACKGROUND AND OBJECTIVE: The benefits of domiciliary non-invasive ventilation (NIV) post lung transplantation (LTx) have not previously been described. This was a single-centre retrospective audit of patients requiring domiciliary NIV post-LTx. Our aim was to describe indications for NIV and outcomes in chronic lung allograft dysfunction (CLAD) and diaphragmatic palsy. METHODS: All patients requiring domiciliary NIV post-LTx between 2010 and June 2016 were assessed. NIV indications, respiratory function and patient outcomes were collected. RESULTS: Out of 488 LTx recipients, 20 patients were identified as requiring NIV over the 6.5-year study period. The most common indications for NIV were CLAD and diaphragmatic palsy. Hypercapnia improved significantly with NIV. Patient outcomes were poor with nine (45%) patients dying, four (20%) undergoing redo-LTx, four (20%) continuing domiciliary NIV and only three (15%) patients weaned off NIV. CONCLUSION: This is the first case series to describe the use of domiciliary NIV post-LTx. Patients commenced on NIV post-LTx had severely impaired lung function and severe hypercapnia. Patients with diaphragmatic palsy often recovered. The mortality rate was high in chronic allograft dysfunction.

Continued Successful Evolution of Extended Criteria Donor Lungs for Transplantation.

BACKGROUND: In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what outcomes can be achieved without EVLP, by taking an aggressive approach to donor use to maximize lung transplantation. METHODS: Data for all lung transplant donor referrals to the Alfred Hospital in Melbourne, Australia were collected for 2012 to 2013. Donor variables were analyzed and calculated into a previously validated lung donor score. Lung transplant recipient outcome data included the following: primary graft dysfunction; duration of mechanical ventilation; need for cardiopulmonary bypass extracorporeal membrane oxygenation; intensive care and hospital length of stay; 30-day, 1-year, and 3- to 4-year survival rates; rates of acute rejection and chronic lung allograft dysfunction; and peak and 12-month lung function (forced expiratory volume in 1 second). RESULTS: Of the 318 lung donor offers, 129 resulted in successful lung transplantation, with an overall donor use rate of 41%. There was no correlation between donor score and any of the recipient outcomes, and excellent short-term and longer-term survival was achieved. CONCLUSIONS: Future studies examining lung transplantation outcomes with EVLP must consider the excellent results that can be achieved by using marginal lungs and conventional donor management. It is important to consider that adopting a strategy of perioperative lung donor evaluation and intervention allows use of what are considered marginal lungs to achieve promising results.

Long-term outcomes from bronchoscopic lung volume reduction using a bronchial prosthesis.

BACKGROUND AND OBJECTIVE: We evaluated long-term safety and lung function outcomes in a cohort of patients with severe upper-zone heterogeneous emphysema who underwent bronchoscopic lung volume reduction (BLVR) performed with the Emphasys one-way valve. METHODS: A retrospective cohort study was undertaken to assess long-term outcomes in 23 consecutive patients who underwent upper lobe BLVR between July 2001 and November 2003 as part of a first-in-humans study. Long-term follow up (>12 months) was available in 16/23 patients (median duration of follow up 64 months (range 15-90 months)). Both unilateral (n=4) and bilateral (n=12) BLVR procedures were performed with a mean of 6 (range 3-11) valves being inserted. Changes in pulmonary function tests were assessed longitudinally following the procedure. RESULTS: 13/16 and 11/16 patients showed post-procedure improvements in FEV1 and DL(CO) , respectively. However, early improvements in pulmonary function were not sustained with only 6/16 patients still showing improved lung function at the end of follow up. There were no significant improvements in other indices of pulmonary function. Three patients, in the absence of clinical benefit, proceeded to lung transplantation at 15, 16 and 44 months post BLVR. Four patients died during the course of the study at 27, 29, 39 and 50 months post procedure. CONCLUSIONS: BLVR with the Emphasys one-way valve has an acceptable safety profile and in select patients may achieve long-term sustained improvements in pulmonary function.