Československý transplantační kongres
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1. československý transplantační kongres 2. československý transplantační kongres |
Konferenční abstrakta 2006
Abstrakta přednášek – satelitní sympózia
SYMPHONY – THE LANDMARK STUDY (RESULTS FROM THE LARGEST RANDOMIZED PROSPECTIVE STUDY IN DE NOVO KIDNEY TRANSPLANTATION
Ekberg H.
Lund University, Malmö, Sweden
The CAESAR study showed that the use of low-dose cyclosporine A (CsA) in combination with daclizumab, mycophenolate mofetil (MMF, CellCept®) and corticosteroids is safe and effective. However, complete CsA withdrawal at 4-6 months after transplantation was associated with an increased risk of acute rejection1. Thus, a balance needs to be found between reducing toxicity and maintaining efficacy.
The main objective of the Symphony trial was to determine whether low doses of CNIs or sirolimus (SRL) in conjunction with MMF and daclizumab may be beneficial in comparison with standard-dose CsA-based immunosuppression. The study aimed at demonstrating improved renal function while at the same time providing an acceptable rate of acute rejection and a favourable safety profile. Symphony is the largest ever prospective study in de novo renal transplant patients. In the Symphony study, 1645 adult patients were randomised to receive one of the following treatments: standard-dose CsA (target trough level 150-300 ng/ml for 3 months, 100-200 ng/ml thereafter), 1g bid MMF and corticosteroids (Group A), or daclizumab induction (2mg/kg followed by 4 x 1mg/kg every 2 weeks), 1 g bid MMF and corticosteroids in combination with either low-dose CsA (50-100 ng/ml; Group B), low-dose TAC (3-7 ng/ml; Group C) or low-dose SRL (4-8 ng/ml; Group D). Differences in glomerular filtration rate (GFR) and biopsy-proven acute rejection (BPAR) were statistically significant among the 4 groups (p < 0.0001).
The low-doseTAC group was significantly superior to all other groups with respect to mean calculated GFR, as measured by Cockcroft-Gault (65.6 ml/min compared with 56.7-59.7 ml/min) at 12 months. The lowest incidence of BPAR at 12 months (12% compared with 24-37%) was also observed in the low-dose TAC group. In addition, 12-month graft survival was significantly better in this treatment group than in the standard-dose CsA (94% vs 89%, p = 0.0108) and the low-dose SRL groups (94% vs 89%, p = 0.0115). No significant differences in patient survival were observed between the 4 treatment groups. The safety profile was similar between the treatment groups with no significant differences in most of the parameters measured. In patients receiving low-dose TAC, significantly higher incidences of diarrhoea (26% vs 15-22%, p = 0.0003) and diabetes mellitus (11.5% vs 5.7-8.6%) were observed, whereas in patients receiving low-dose SRL a significantly higher incidence of lymphoceles (12.9% vs 3.6-6.0%, p < 0.0001) was detected. The Symphony study proves that MMF with low-dose TAC maximises the function and longevity of the organ. This combination protects the patient by providing the best balance between efficacy and toxicity available to date.
References:
1. Ekberg H. Transplantation 2004; 78 (Suppl.):458-9 (Abs. P734).
2. Ekberg H. World Transplant Congress 2006, Boston, USA.