Torque teno viruses (TTV) are small DNA-viruses, of the genus Alphatorquevirus, whose replication is linked to immune status. TTV load may be an indicator for efficacy of IS in lung transplant recipients (LTRs). In a prospective single-center-study 143 LTRs were followed up and tested by quantitative TTV-DNA PCR. Using multivariate Cox-regression contribution of TTV-load to the occurrence of severe infections, chronic lung allograft dysfunction (CLAD), acute cellular rejection (ACR), and death was assessed. During follow-up 28 (20%) patients developed infections with a rate of 7.7 per 100 patient-years (PY). The hazard-ratio (HR) associated with a one-log10 increase of TTV-load before the event was 5.05. CLAD occurred with a rate of 6.0%-PY. HR for a 1 log10 increase of the lowest TTV level before the event was 0.71 (CI: 0.54–0.93). TTV-load predicts clinical events and may be useful to optimize IS during the first years of follow-up of LTRs.
Despite the progress made in medical therapies for treating pulmonary hypertension (PH), a subset of patients remain susceptible to developing a maladaptive right ventricular phenotype. The effective management of end-stage PH presents substantial challenges, necessitating a multidisciplinary approach and early identification of patients prone to acute decompensation. Identifying potential transplant candidates and assessing the feasibility of such a procedure are pivotal tasks that should be undertaken early in the treatment algorithm. Inclusion on the transplant list is contingent upon a comprehensive risk assessment, also considering the specific type of PH and various factors affecting waiting times, all of which should inform the decision-making process. While bilateral lung transplantation is the preferred option, it demands expert intra- and post-operative management to mitigate the heightened risks of pulmonary oedema and primary graft dysfunction in PH patients. Despite the availability of risk assessment tools, the occurrence of acute PH decompensation episodes can be unpredictable, potentially leading to refractory right ventricular failure even with optimal medical intervention, necessitating the use of rescue therapies. Advancements in right ventricular assist techniques and adjustments to graft allocation protocols for the most critically ill patients have significantly enhanced the survival in intensive care, affording the opportunity to endure while awaiting an urgent transplant. Given the breadth of therapeutic options available, specialised centres capable of delivering comprehensive care have become indispensable for optimising patient outcomes. These centres are instrumental in providing holistic support and management tailored to the complex needs of PH patients, ultimately enhancing their chances of a successful transplant and improved long-term prognosis.
The value of induction therapy in lung transplantation is controversial. According to the ISHLT, only about 50% of patients transplanted within the last 10 years received induction therapy. We reviewed our institutional experience to investigate the impact of induction therapy on short- and long-term outcomes. Between 2007 and 2015, 446 patients with a complete follow-up were included in this retrospective analysis. Analysis comprised long-term kidney function, infectious complications, incidence of rejection and overall survival. A total of 231 patients received alemtuzumab, 50 patients antithymocyte globulin (ATG) and 165 patients did not receive induction therapy (NI). The alemtuzumab group revealed the lowest rate of chronic kidney insufficiency (NI: 52.2%; ATG: 60%; alemtuzumab: 36.6%; p = 0.001). Both, the NI group (p<0.001) and the ATG group (p = 0.010) showed a significant increase of serum creatinine during follow-up compared to alemtuzumab patients. Furthermore, alemtuzumab group experienced the lowest rate of infection in the first year after transplantation. Finally, improved survival, low rates of acute cellular rejection (ACR), lymphocytic bronchiolitis (LB) and chronic lung allograft dysfunction (CLAD) were found in patients treated either with alemtuzumab or ATG. Alemtuzumab induction therapy followed by reduced maintenance immunosuppression is associated with a better kidney function compared to no induction and ATG. Survival rate as well as freedom from ACR and CLAD were comparable between alemtuzumab and ATG.
Extracorporeal photopheresis (ECP) is used by few lung transplant centers to treat chronic lung allograft dysfunction (CLAD). Although reported results suggest a beneficial effect on CLAD progression, evidence is limited to single center experiences. The aim of this study is to analyze outcomes of ECP in a large multicenter European cohort. The primary endpoint was patient survival after initiation of ECP. This study included 631 patients, 87% suffered from bronchiolitis obliterans syndrome (BOS), and 13% had restrictive allograft syndrome (RAS). Long-term stabilization was achieved in 42%, improvement in 9%, and no response in 26%. Within the first 12 months of therapy, 23% of patients died. Patients’ survival after initiation of ECP at 5 years was 56% in stable, 70% in responders, and 35% in non-responders (p= 0.001). In multivariable Cox regression, both stabilization (HR: 0.48, CI: 0.27–0.86,p= 0.013) and response (HR: 0.11, CI: 0.04–0.35,p< 0.001) to ECP were associated with survival. Absolute FEV1 at baseline was also protective (HR: 0.09, CI: 0.01–0.94,p= 0.046). RAS phenotype was the only risk factor for mortality (HR: 2.11, 1.16–3.83,p= 0.006). This study provides long-term outcomes of ECP use in CLAD patients in the largest published cohort to date. Two-thirds of the cohort had a sustained response to ECP with excellent long-term results.