February 2012 Transplant Trial Watch now online
Posted by Simon Knight on February 3, 2012
The February 2012 Transplant Trial Watch is now online. Each month, the CET staff pick 10 recent randomised trials in transplantation and summarise them, assessing the methodological quality.
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.
Give a Kidney – promoting altruistic donation in the UK
Posted by Simon Knight on January 11, 2012
Give a Kidney – One’s Enough is a charity that aims to raise awareness of altruistic living kidney donation. Altruistic donation is the giving of a kidney, from a living person, to a stranger who has kidney failure. The charity also aims to publicise why more living kidney donors are needed and to support people who are considering this type of donation.
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.
Don’t miss the deadline for EVIT 2012 applications!
Posted by Simon Knight on January 11, 2012
The next Evidence in Transplantation Course (EVIT) will be held in London on March 16-17. The joint CET and ESOT course, now in it’s fourth year, have received excellent reviews from past participants, and aims to increase skills in evidence-based decision making. It includes sessions on clinical trial design and interpretation, literature searching, literature appraisal, systematic review and meta-analysis.
For more information and application, go to the ESOT website. The application deadline ends 15 January.
January Transplant Trial Watch now online
Posted by Simon Knight on January 9, 2012
The first Transplant Trial Watch of 2012 is now available on the CET website. This month’s RCTs include studies of donor pretreatment, immunosuppressive regimens and CMV prophylaxis.
Successful transplantation of a tracheobronchial airway
Posted by Peter Morris on December 9, 2011
This fascinating report appeared in the Lancet on line in the last couple of weeks (Jungebluth et al Nov 24, 2011). This is a single case report from a team led by Paolo Macchiarini who three years ago reported the first tissue engineered tracheal transplantation with a non immunogenic scaffold of allogeneic human donor trachea reseeded with bone marrow derived mesenchymal stem cells. A 36 year old male patient, previously treated for a tracheal tumour with debulking surgery and radiation therapy was referred with stridor; scans showed an extensive recurrent tumour involving the lower 5 cm of the trachea and extending into the right bronchus.
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 5th 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.
Interleukin-2 and regulatory T cells
Posted by Peter Morris on December 9, 2011
In the December 1st issue of the New England Journal of Medicine are two very interesting reports. The first from Koreth et al (2011; 365:2055-66) has studied the use of low dose interleukin-2 (IL-2) in chronic graft versus host disease following allogeneic haematopoietic stem cell transplantation for haematologic cancer that was resistant to steroid therapy. Patients received subcutaneous IL-2 at three dose levels but all representing low doses of IL2. All patients had a major increase in the population of T regulatory (Treg) cells and of the 29 patients enrolled a number had a significant clinical response.
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.
December Transplant Trial Watch now online
Posted by Simon Knight on December 7, 2011
The December edition of the Transplant Trial Watch is now available on the CET website.
This month, ten new important trials in the fields of Renal and Hepatic transplantation are listed and assessed for quality.
November Transplant Trial Watch now online
Posted by Simon Knight on November 4, 2011
The November edition of Transplant Trial Watch is now available on the CET site.
Each month, the CET staff summarise and appraise for quality ten of the most important trials published in the transplant literature.
Industry sponsored symposia
Posted by Peter Morris on October 22, 2011
There were a number of corporate symposia at the ESOT Congress, which is accepted practice these days at most large meetings. However I did hear a lot of criticism about the biased presentations made at some of these symposia, which I had not heard before! Certainly I went to one sponsored by Astellas which was really a quite clever advertisement for the long acting formulation of tacrolimus, Advagraf. The speakers, all distinguished, did present valid data but in my opinion were very selective in their presentations all directed at eventually building up an argument in favour of the prolonged-release formulation of tacrolimus, Advagraft (it should be noted that Prograf, the immediate-release formulation of tacrolimus is about to come off patent!).
This is not without precedent, but I am becoming increasingly concerned as corporate symposia in the past tended to be much more educational than appears to be the case now. I also feel strongly in this age of transparency that speakers should declare up front how much they are being paid for giving their talk. I think this would help the audience to put their presentations in perspective.. The support of industry is important for our congresses, but I do think we need to carefully look at the impact of big pharma on our practice as there is no question that immunosuppression in transplantation is driven to a very considerable extent by industry, not always based on the soundest evidence. This is a plea for transparency at all levels.
The ESOT congress in Glasgow
Posted by Peter Morris on October 8, 2011
I have just returned from the ESOT 2011 Congress in Glasgow. It was held in the very large congress centre (SECC) on the banks of the Clyde River in Glasgow. The SECC is a very impressive centre with one building containing the major auditoria and which resembles from the outside a mini edition of the Sydney Opera House, while a second connecting building has space for all the other activities such as the exhibition hall, mini lecture theatres and meeting rooms.
The meeting itself was absolutely first class and I felt it was the best ESOT Congress ever, with over 3,500 participants. Of note was the large number of participants from outside Europe, confirming the increasing international stature of ESOT. Many innovations were introduced. These included poster sessions on an electronic screen at which the authors spoke, giving a brief 3 minute presentation and then there were a number of mini theatres which hold about 20-30 people and where short presentations took place. You could even download the scientific programme as an app on your smartphone. There was also streaming of many of the key plenary sessions, even to members of the AST in the USA.
The local organising committee comprised Professors John Forsythe and Alan Jardine as co chairmen backed up by Professors Peter Friend, Keith Rigg, Anthony Warrens and Chris Watson. They had put an enormous amount of work into organising the scientific programme, and indeed fulfilled their advance notice that this was to be a new meeting! Furthermore the Chief Executive officer, Annalisa Ponchia, and her team, Chiara and Kate, had done a tremendous job with the administrative and social side of the congress. All in all this was a great success and a great occasion for the President, Professor Rutger Ploeg.