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P-18.38 Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation

Natalia Riva, Argentina

Hospital de Pediatria JP Garrahan

Abstract

Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation

Natalia Riva1,2, Guido Trezeguet Renatti1, Veronica Meza3, Maria Gole3, Hayellen Reijenstein3, Valeria Gonzalez1, Julia Minetto3, Nieves Licciardone4, Marcelo Dip3, Paula Schaiquevich1,2, Esteban Halac3, Oscar C. Imventarza3.

1Precision Medicine Laboratory, Hospital de Pediatria Prof Dr JP Garrahan, Buenos Aires, Argentina; 2National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina; 3Liver Transplantation, Hospital de Pediatria Prof Dr JP Garrahan, Buenos Aires, Argentina; 4Laboratory, Hospital de Pediatria Prof Dr JP Garrahan, Buenos Aires, Argentina

Basiliximab, a monoclonal anti-interleukin-2 receptor antibody, has demonstrated its potential in reducing acute cellular graft rejection in adult liver and kidney graft recipients. Its introduction into the clinics is based on the fact that steroids can be significantly reduced in transplant patients, reducing their adverse events and morbidity especially important in the pediatric population. The aim of this study was to retrospectively analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme in pediatric liver transplant patients.
Patients transplanted de novo between 2011 and 2017 with biliary atresia, were included. The primary endpoints were the occurrence of the first biopsy-proven acute rejection episode (BPAR) and steroids requirements in the immunosuppressive treatment during the first 6 months post transplant. Peritransplant variables included demographic, clinical, and pharmacological parameters over a 6 month follow-up period. Variability in tacrolimus levels was calculated using percent coefficient of variation and tortuosity. Steroid and BPAR-free survival rates were calculated using the Kaplan–Meier method, and risk factors were identified by multivariate Cox regression models.
In total, 44 liver-transplanted patients with biliary atresia who received basiliximab after reperfusion and on day 4 post surgery were analyzed. During the follow-up, 31 patients (70.5%) required steroids due to BPAR (68%, n=21), liver dysfunction without biopsy (26%, n=8) and tacrolimus induced nephrotoxicity (6%, n=2). Steroid-free survival at 6 months post-transplant was 29.5% (95%CI,16.9-43.2). Tacrolimus tortuosity was associated with a 116% increased risk of steroids requirements [(hazard ratio (HR), 2.2; 95%CI, 1.5-3.2; p<0.05)
BPAR-free survival at 6 months post-transplant was 43.2% (95%CI, 28.4-57.1). BPAR was significantly associated with tacrolimus tortuosity (HR 2.9; 95%CI, 1.6-5.3) and post-transplant complications requiring an early surgical intervention (HR 3.2; 95%CI 1.4-7.0). In the sub-population without surgical complications (n=28), BPAR-free survival at 6 months post transplant was 57.1% (95%CI, 37.1-72.9). Steroid-free survival at 6 months post transplant was 28.6% (95%CI, 13.5-45.6). In this subpopulation also, tortuosity was significantly associated with an increased risk of BPAR (HR 2.0; 95%CI 1.4-2.9) and steroid requirements (HR 2.6; 95%CI 1.5-4.6).
Altogether, the use of basiliximab in combination with tacrolimus in a pediatric liver transplant cohort, avoided steroid requirements in about 30% of the patients during the first 6 months post transplant. Surgical complications and tacrolimus variability independently increased the risk of BPAR development. Moreover, tacrolimus variability also increased the risk of steroid requirements. Further efforts should be focused to reduce tacrolimus variability and optimize the immunosuppressive treatment according to individual requirements.

National Central Coordinator Institute of Ablation and Implant (INCUCAI).

References:

[1] Gras J, et al. Liver Transplantation. 2008 : 14:469-477
[2] Crins ND, et al. Pediatr Transplantation. 2014: 18: 839–850

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