Adenovirus-Specific T Cells for Steering of Immunosuppression After Pediatric Kidney Transplantation in the Randomized Controlled Ivist Trial
1Pediatrics II, University Hospital of Essen, Essen, Germany, 2Institute of Biostatistics, Hannover Medical School, Hannover, Germany, 3Pediatric Nephrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany, 4Pediatric Nephrology, University of Colgne, Köln, Germany, 5Pediatric Nephrology, University Hospital of Rostock, Rostock, Germany, 6Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany, 7Institute for Clinical Pharmacology, Hannover Medical School, Hannover, Germany
Meeting: 2021 American Transplant Congress
Abstract number: 452
Keywords: FACS analysis, Immunosuppression, Pediatric, T cells
Topic: Clinical Science » Kidney » Kidney: Pediatrics
Session Information
Session Name: Kidney Alloimmune Responses
Session Type: Poster Video Chat
Date: Monday, June 7, 2021
Session Time: 7:30pm-8:30pm
Presentation Time: 7:50pm-8:00pm
Location: Virtual
*Purpose: Pharmacokinetic monitoring alone is insufficient to estimate the intensity of immunosuppression after pediatric kidney transplantation (Tx). Levels of virus-specific T cells (Tvis) have been shown to identify over-immunosuppression. Our IVIST trial has demonstrated that the additional steering of immunosuppressive therapy by Tvis levels is safe and reduces exposure to immunosuppressive drugs with significantly lower trough levels without increasing the risk of acute rejections.
*Methods: In our multicenter, randomized controlled IVIST trial, 64 pediatric kidney recipients (10.8±4.2 years) were randomized 1:1 to a control group with trough level monitoring of immunosuppressants or to an intervention group with additional steering by CD4 Tvis levels against adenovirus (ADV), cytomegalovirus (CMV) and herpes simplex virus (HSV). CD4 Tvis were quantified by cytokine flow cytometry in 20 visits during the two-year study period. We have analyzed the CD4 Tvis levels and the number of Tvis-based dose adjustments of the immunosuppressive drugs.
*Results: At time of Tx ADV-Tvis were detectable in 30/31 patients of the intervention group, CMV-Tvis and HSV-Tvis only in 12/31. No significant ADV DNAemia was found, whereas five primary CMV infections with excessive boost of CMV-Tvis were observed. The mean level of ADV-CD4 Tvis was 1.63 (SD 1.25), 2.03 (SD 1.8), 2.18 (SD 2.51) and 1.97 cells/µl (SD 1.34) 1, 6, 12 and 24 months after Tx. The median number of dose reductions of immunosuppressants based on Tvis <2 cells/µl was 4 (range 0-10) per patient. In the intervention group a total of 125 Tvis-based dose reductions was performed in 28/31 children. 42.4% of the dose reductions were done in the first 6 months, 35.2% between month 7 and 12 and 22.4% in the second year after transplantation.
*Conclusions: Under the intensified immunosuppression during the initial post-Tx period low CD4 Tvis levels were observed with subsequent increase after dose reductions of the immunosuppressive therapy. ADV-Tvis are most suitable for immune monitoring considering their high prevalence (even in a pediatric cohort) and stability because of the absence of post-Tx ADV infections. Routine monitoring of CD4 Tvis is predominantly recommendable in the first post-Tx year to prematurely identify over-immunosuppression.
To cite this abstract in AMA style:
Ahlenstiel-Grunow T, Liu X, Schild R, Oh J, Taylan C, Weber LT, Staude H, Verboom M, Schröder C, Sabau R, Großhennig A, Pape L. Adenovirus-Specific T Cells for Steering of Immunosuppression After Pediatric Kidney Transplantation in the Randomized Controlled Ivist Trial [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/adenovirus-specific-t-cells-for-steering-of-immunosuppression-after-pediatric-kidney-transplantation-in-the-randomized-controlled-ivist-trial/. Accessed May 12, 2025.« Back to 2021 American Transplant Congress