Bestard, Oriol and Meneghini, Maria and Crespo, Elena and Bemelman, Frederike and Koch, Martina and Volk, Hans D. and Viklicky, Ondrej and Giral, Magali and Banas, Bernhard and Ruiz, Juan C. and Melilli, Edoardo and Hu, Liu and van Duivenvoorden, Raphael and Nashan, Bjorn and Thaiss, Friedrich and Otto, Natalie M. and Bold, Gantuja and Stein, Maik and Sefrin, Anett and Lachmann, Nils and Hruba, Petra and Stranavova, Lucia and Brouard, Sophie and Braudeau, Cecile and Blancho, Gilles and Banas, Miriam and Irure, Juan and Christakoudi, Sophia and Sanchez-Fueyo, Alberto and Wood, Kathryn J. and Reinke, Petra and Grinyo, Josep M. (2021) Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial. AMERICAN JOURNAL OF TRANSPLANTATION, 21 (8). pp. 2833-2845. ISSN 1600-6135, 1600-6143
Full text not available from this repository. (Request a copy)Abstract
Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-gamma ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E-) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E- (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E- patients, notably E-/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E-/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; biomarker; clinical decision-making; clinical research/practice; clinical trial; immunobiology; immunosuppression/immune modulation; immunosuppressive regimens - minimization/withdrawal; kidney transplantation/nephrology; rejection: acute |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 12:15 |
| Last Modified: | 27 Sep 2022 12:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48074 |
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