This month, trials include RCTs investigating the safety and efficacy of Advagraf and Belatacept in renal transplant recipients, and trial looking at steroid pretreatment of liver donors.

The App also allows you to send trials of interest to your colleagues via email and store your favourites for later viewing. There are links to the publishers site for abstracts and full text (access permitting).

Search the Apple App Store or Google Play Store for “Transplant Trial Watch” and download it now!

This month, there are a number of trials looking at immunsuppression monitoring and factors affecting exposure, as well as an interesting trial looking at the benefits of antimuscarinics in renal transplant recipients with small volume bladders.

More information can be found on the King’s College London website.

This month, there are trials in renal, hepatic and cardiac transplantation, including a comparison of CsA/AZA and Tac/MMF in renal transplant recipients and the impact of MMF pre-treatment in live-donor renal transplantation.

Patients with kidney failure have the option of dialysis or transplantation when both their kidneys fail. A kidney transplant can provide patients with freedom from regular dialysis, a better quality of life and longer life expectancy. Unfortunately, very few patients have someone who can give them a kidney, and on average most patients have to wait on dialysis for two to three years before a kidney becomes available on the national deceased donor transplant waiting list.

Although the UK performs more than 2500 kidney transplantations a year, there are over 7000 people waiting for a kidney transplant, of whom 300 die each year. Initiatives like this to promote living donation – both altruistic and directed, aim to improve the quality of organ donation and reduce this wait.

For more information and application, go to the ESOT website. The application deadline ends 15 January.

A synthetic scaffold of the trachea and bronchi of the appropriate size as determined by imaging of the patient’s own trachea was made in a bioreactor over a bifurcated mandril using a nanocomposite polymer. This was seeded with autologous mononuclear cells from the patient’s bone marrow 36 hours before transplantation was to take place. Immediately before transplantation a second bone marrow harvest was done and mononuclear cells were separated and  the graft was reseeded with these newly obtained mononuclear cells. Granulocyte colony stimulating factor (GCSF) and epoetin beta were used to enhance the growth of the seeded cells.

At transplantation an extensive resection was done, which also included resection of the right intrapericardial pulmonary artery which was replaced by a Dacron graft. All the tumour margins were negative on frozen section. The synthetic reseeded airway was implanted with anastomosis to the right and left main bronchi and then to the proximal trachea. The patient was treated with subcutaneous injections of GCSF and epoetin-alpha starting the day before transplantation and every other day for two weeks. The immediate post operative recovery was complicated with a right upper lobe pneumonia which responded to antibiotic treatment and the patient was weaned of mechanical ventilation on the 5^th post operative days. The patient is now 5 months after transplantation, is asymptomatic, breathing normally and is tumour free on scanning. Lung function is improved compared to the preoperative evaluation.

This is an exciting report, particularly bearing in mind that this was by standard criteria, a non-resectable tumour of the trachea. As the new trachea is a synthetic material seeded with autologous cells there is no requirement for immunosuppression and this must improve the chances of there being no tumour recurrence. There is no question that this is a novel approach for the resection of an otherwise inoperable tumour of the trachea and is an exciting development in tissue engineering.

The second study from Saadoun et al (2011;365:2067-77) investigated the use of low dose IL-2 in 10 patients with hepatitis C virus (HCV) induced vasculitis that was resistant to conventional anti viral therapy, rituximab therapy or both. There was an increase in Treg cells in these patients and there was a reduction in cryoglobulinemia in 9 of the 10 patients and an improvement in vasculitis in 8 of the 10 patients in the study. There were no adverse effects.

These two studies are of course very much phase 1 studies but are good examples of what may become a feasible therapy in patients with conditions associated with an immune dysfunction and a deficiency of Treg cells. In the same issue Jeffrey Bluestone has written an excellent editorial covering these two papers and others that are relevant. The title of his editorial is the “Yin and Yang of Interleukin-2 mediated immunotherapy” This is very appropriate in that we are already familiar with the fact that IL-2 can lead to an expansion of effector cells in high doses but in low doses it stimulates the proliferation of Treg cells. He points out that overall, low dose IL2 appears to be safe and that serious complications or infections occurred in very few patients. Furthermore increasing Treg cells did not lead to a recurrence of hematologic cancer in the patients with graft versus host disease although the graft versus host disease was suppressed nor in the HCV vasculitis patients was there any evidence of a worse viral load following the expansion of the Treg population. However long term follow up is required to see if the delicate balance between Treg and T effector cells is maintained.

As interest in Treg cells and their potential use in immunotherapy grows, these two papers do represent a significant contribution to our knowledge in this area.