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2016 - IPTA Fellows Meeting


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Mini Oral Abstract Presentations

18.64 - Empiric Use of Sirolimus in Pediatric Heart Transplantation Recipients

Presenter: Adam, Putschoegl, Rochester, United States
Authors: Adam Putschoegl, Jonathan Johnson

Empiric Use of Sirolimus in Pediatric Heart Transplantation Recipients

Adam Putschoegl1, Jonathan Johnson1.

1Pediatric Cardiology, Mayo Clinic, Rochester, MN, United States

Introduction: Sirolimus has been reported in heart transplant patients with cardiac allograft vasculopathy (CAV) and calcineurin inhibitor (CNI)-induced nephropathy.  Sirolimus has theoretical benefits including an overall reduction of CAV burden in adult studies. However, little is known regarding the use of sirolimus empirically in children after heart transplantation.  Here, we report our updated experience with the empiric use of sirolimus in pediatric heart transplantation recipients.

 

Materials and Methods: In this retrospective review, we examined all pediatric heart transplant patients for whom we attempted conversion to a CNI-free sirolimus-based regimen. Patients were treated routinely with an anti-metabolite medication (azathioprine or mycophenolate) in addition to sirolimus, with or without steroids.

 

Results and Discussion: We identified 27 patients (mean age at transplant 7.8 years, range 0.1–21 yrs, 48% female) for whom we attempted conversion to a sirolimus-based, CNI-free regimen an average of 34±44 months post-transplant. Of these 27, six patients had to discontinue sirolimus due to side effect (pneumonitis, aphthous ulcers, proteinuria, and dactylitis), and three had tacrolimus added back due to rejection or to help reduce side effects of sirolimus.  The remaining 18 patients (mean age at transplant 6.3 years, range 0.1–21 yrs, 39% female) were successfully converted over a period of 69±43 days to the CNI-free immunosuppressive protocol. Follow-up was available for an average of 4.4±3 years post-conversion.  For these 18 patients, there was no significant difference between the rate of rejection while taking CNIs prior to conversion (0.18 rejections per patient years) compared to post-conversion (0.3 rejections per patient years).  Glomerular filtration rate increased from 86±38 mL/min pre-conversion to 92±30 mL/min post-conversion and 93±39 at latest follow-up; however this did not reach statistical significance.

 

Conclusion: In this small retrospective cohort, a CNI-free sirolimus-based immunosuppressive regimen was not associated with an increased rejection rate or change in markers of renal function, though side effects required discontinuation in six patients.  The use of sirolimus as a primary agent in pediatric heart transplant patients merits further evaluation.

References:

[1] Raichlin E, Khalpey Z, Kremers W, Frantz RP, Rodeheffer RJ, Clavell AL, et. al. Replacemnt of calcineurin-inhibitors with sirolimus as primary immunosupressionin in stable cardiac transplant recipients. Transplantation. 2007. 84(4): p.467-74.
[2] Kushwaha SS, Khalpey Z, Frantz RP, Rodeheffer RJ, Clavell AL, Daly RC, et. al. Sirolimus in cardiac transplantation: use as a primary immunosuppressant in calcineurin inhibitor-induced nephrotoxicity. J Heart Lung Transplant. 2005. 24(12): p. 2129-36.
[3] Raichlin E, Bae JH, Khalpey Z, Edwards BS, Kremers WK, Clavell AL, et. al. Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation. 2007. 116(23): p. 2726-33.
[4] Morelon E and Kreis H, Sirolimus therapy without calcineurin inhibitors: Necker Hospital 8-year experience. Transplant P. 2003. 35(3 Suppl): p. 52S-57S.
[5] Raichlin E, Prasad A, Kremers WK, Edwards BS, Rihal CS, Lerman A, et. al. Sirolimus as primary immunosuppression is associated with improved coronary vasomotor function compared with calcineurin inhibitors in stable cardiac transplant recipients. Eur Heart J. 2009. 30(11): p. 1356-63.
[6] Topilsky Y, Hasin T, Raichlin E, Boilson BA, Schirger JA, Pereira NL, et. al. Sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation. Circulation. 2012. 125(5): p. 708-20.


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