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Abstract: PO2189

Steering of Immunosuppression by Virus-Specific T Cells After Pediatric Kidney Transplantation (KTx) in the Randomized Controlled IVIST Trial

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Pape, Lars, Universitat Duisburg-Essen Medizinische Fakultat, Essen, Nordrhein-Westfalen, Germany
  • Ahlenstiel-Grunow, Thurid, Universitat Duisburg-Essen Medizinische Fakultat, Essen, Nordrhein-Westfalen, Germany
Background

Pharmacokinetic monitoring alone is insufficient to estimate the intensity of immunosuppression after KTx. Levels of virus-specific CD4 T cells(CD4Tvis) have been shown to identify overimmunosuppression. The IVIST trial has demonstrated that additional steering of immunosuppressive therapy by CD4Tvis levels is safe and reduces exposure to immunosuppressants with significantly lower trough levels but without increasing the risk of acute rejections.

Methods

In the randomized controlled IVIST trial, 64 pediatric KTx recipients were randomized 1:1 to a control group with trough level monitoring of immunosuppressants or to an intervention group with additional steering by CD4Tvis levels against adenovirus(ADV), cytomegalovirus(CMV) and herpes simplex virus(HSV). The immunosuppression consisted of cyclosporine A, everolimus and glucocorticoids. CD4Tvis were quantified by cytokine flow cytometry in 20 visits during the two-year study period. In the intervention group we have analyzed the CD4Tvis levels and the number of Tvis-based dose adjustments of immmunosuppressants.

Results

At time of transplantation, ADV-CD4Tvis were detectable in 30/31 patients (intervention group), CMV-CD4Tvis and HSV-CD4Tvis only in 12/31. No significant ADV- or HSV-DNAemia was found; only two patients showed transient CMV-DNAemia based on CMV-reactivation. Five primary CMV-infections with seroconversion and boost of CMV-CD4Tvis were observed without significant CMV-DNAemia. The mean level of ADV-CD4Tvis was 1.63(SD1.25), 2.03(SD1.8), 2.18(SD2.51) and 1.97 cells/µl(SD1.34) 1,6,12 and 24 months after KTx. In case of CD4Tvis <2cells/µl 125 dose reductions of immunosuppressants (96% based on ADV-CD4Tvis) were performed in 28/31 children with a median of 4 Tvis-based dose reductions (range 0-10) per patient. 48% of these were carried out in the first six months.

Conclusion

Under the intensified immunosuppression during the initial post-KTx period low ADV-CD4Tvis levels were observed with subsequent increase after dose reduction of the immunosuppression. ADV-CD4Tvis are most suitable for immune monitoring because of their high prevalence (even in children) and stability combined with absence of ADV-DNAemia. Routine monitoring of ADV-CD4Tvis is recommendable especially in the first post-KTx year to prematurely identify overimmunosuppression.

Funding

  • Government Support – Non-U.S.