P.130 A single center experience in using sirolimus in pediatric liver transplant
Saturday May 04, 2019 from 18:30 to 20:00
Exhibit-Poster Area
Presenter

Rayna Alamurova, Bulgaria

Clinical Fellow in Paediatric Hepatology

Children's Liver Unit

Leeds General Infirmary

Abstract

A single center experience in using sirolimus in pediatric liver transplant

Rayna Alamurova1, Sanjay Rajwal1, Suzanne Davison1, Penny North-Lewis1, Patricia McClean1.

1Children's Liver Unit, Leeds Children's Hospital, Leeds, United Kingdom

Introduction: Sirolimus (rapamycin) is a macrolide immunosuppressive agent. It supresses the T-cell response to IL-2 by binding to and inhibiting the mechanistic target of rapamycin (mTOR). Sirolimus (SRL) has been used in children after solid organ transplantation. There are only a small number of studies on mTOR inhibitor-based maintenance immunosuppression in paediatric liver transplant recipients. 

Methods: Retrospective review of medical records of paediatric liver transplant recipients, who were commenced on SRL between 2011 and 2018. Indications, safety and efficacy were assessed. 

Results: 13 patients received SRL: 1 bile salt export pump (BSEP) disease recurrence (to increase immunosuppression), 2 chronic rejection [ both needed retransplant, 1 then developed posttransplant lymphoproliferative disease (PTLD) so SRL recommenced ], 1 hepatocellular carcinoma (HCC), 2 low glomerular filtration rate (GFR), 7 PTLD, 1 unknown (started in other centre). 9 patients remain on SRL, with mean follow up 31 months ( 8 months - 7 years ), 6 of them with PTLD. SRL was discontinued in : 1 patient with BSEP recurrence, who developed Pneumocystis Carinii Pneumonia (PCP) at 3 months; 1 patient with pulmonary toxicity; 1 patient who required retransplant for chronic rejection and 1 patient had tumour recurrence who died. In PTLD group there was no disease recurrence. 1 patient had acute cellular rejection 2 months post starting SRL. Two patients had septic episodes 1 month post starting SRL, caused by Citrobacter in one and E.coli, Raoutella mixed infection in the other. 1 patient had lymphadenitis within a month and recurrent ear infections later. 2 patients had mild hyperlipidaemia. Renal function stabilized in the 2 children with low GFR, however follow up was short, 1y9m and 2y8m, respectively. Mild hypertension and hyperlipidaemia also resolved on discontinuing SRL. There were no wound healing or vascular complications. Myelosuppression, rashes and mouth ulcers were not seen in patients on SRL.

Conclusion: Our data suggest that SRL has a role in selected paediatric liver transplant recipients but careful monitoring is required.

References:

[1] Harper SJF, Gelson W, Harper IG, Alexander GJM, Gibbs P. Switching to Sirolimus-based immune suppression after liver transplantation is safe and effective:a single-center experience. Transplantation 2011;91:128-132
[2] Gibelli NE, Tannuri U, Pinho-Apezzato ML, Tannuri AC, Maksoud-Filho JG, Andrade WC, Velhote MC, Santos MM, Ayoub AA, Marques da Silva M. Sirolimus in pediatric liver transplantation: a single-center experience. Transplant Proc. 2009 Apr; 41(3):901-3.
[3] Sindhi R, Webber S, Venkataramanan R, McGhee W, Phillips S, Smith A, Baird C, Iurlano K, Mazariegos G, Cooperstone B, Holt DW, Zeevi A, Fung JJ, Reyes J. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus. Transplantation. 2011 Sep 15;72(5):851-5.
[4] Nguyen C, Shapiro R. New immunosuppressive agents in pediatric transplantation. Clinics. 2014;69(51):8-16.
[5] Renner P. mTOR inhibition to prevent posttransplant malignancies - don't stop believin'. Transplantation 2017 Sep; 101(9):1963-1964
[6] Charlton M, Levitsky J, Aqel B, O'Grady J, Hemibach J, Rinella M, Fung J, Ghabril M, Thomason R, Burra P, Little EC, Berenguer M, Shaked A, Trotter J, Roberts J, Rodriguez-Davalos M, Rela M, Pomfret E, Heyrend C, Gallegos-Orozco J, Saliba F. International liver transplantation society consensus statement on immunosuppression in liver transplant recipients. Transplantation. 2018 May; 102(5): 727-743
[7] Monaco AP. The role of mTOR inhibitors in the management of posttransplant malignancy. Transplantation. 2009 Jan 27; 87(2):157-63
[8] De Simone P, Fagiuoli S, Cescon M, De Carlis L, Tisone G, Volpes R, Cillo U; Consensus Panel. Use of Everolimus in liver transplantation: recommendations from a working group. Transplantation. 2017 Feb; 101(2):239-251
[9] Silva HT, Felipe CR, Pestana JOM. Reviewing 15 years of experience with sirolimus. Transplantation research 2015 4:28
[10] Silva HT. The long journey of mTOR inhibitors and the long path that is still ahead. Transplantation. February 2018 - Volume 102 - Issue 2S - p S1 -S2
[11] Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell, Volume 169, Issue 2, 6 April 2017, pages 361-371
[12] Miloh T, Barton A, Wheeler J, Pham Y, Hewitt W, Keegan T, Sanchez C, Bulut P, Goss J. Immunosuppression in pediatric liver transplant recipients: unique aspects. Liver Transpl. 2017; 23(2):244-56.
[13] Stallone G, Infante B, Grandaliano G, Gesualdo L. Management of side effects of sirolimus therapy. Transplantation. 2009 Apr 27; 87(8 Suppl): S23-6.
[14] Vaysberg M, Balatoni CE, Nepomuceno RR, Krams SM, Martinez OM. Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas through modulation of cell-cycle protein expression. Transplantation. 2007 Apr 27; 83(8): 1114-21.
[15] Al-Hussaini A, Tredger JM, Dhawan A. Immunosuppression in pediatric liver and intestinal transplantation: a closer look at the arsenal. J Pediatr Gastroenterol Nutr. 2005 Aug;41(2):152-65.
[16] Nashan B. mTOR inhibition and clinical transplantation: liver. Transplantation. 2018 Febr;102(2S Suppl):S19-S26.
[17] Shenoy S, Hardinger KL, Crippin J, Desai N, Korenblat K, Lisker-Melman M, Lowell JA, Chapman W. Sirolimus conversion in liver transplant recipients with renal dysfunction: a prospective, randomized, single-center trial. Transplantation. 2007 May;83(10): 1389-92.
[18] Zaza G, Granata S, Caletti C, Signorini L, Stallone G, Lupo A. mTOR inhibition role in cellular mechanisms. Transplantation. 2018 Febr; 102 (2S Suppl 1):S3-S16
[19] Sindhi R. Sirolimus in pediatric transplant recipients. Transplantation Proceedings [01 May 2003, 35(3 Suppl):113S-114S]
[20] McKenna GJ, Trotter JF, Klintmalm E, Ruiz R, Onaca N, Testa G, Saracino G, Levy MF, Goldstein RM, Klintmalm GB. Sirolimus and cardiovascular disease risk in liver transplantation. Transplantation. 2013 jan 15; 95(1): 215-21.
[21] Thangarajah D, O'Meara M, Dhawan A. Management of acute rejection in paediatric liver transplantation. Paediatr Drugs. 2013 Dec;15(6):459-71.


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