Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 May 15:23:322-333.
doi: 10.12659/AOT.908243.

A Review of Induction with Rabbit Antithymocyte Globulin in Pediatric Heart Transplant Recipients

Martin Schweiger  1 , Andreas Zuckermann  2 , Andres Beiras-Fernandez  3 , Michael Berchtolld-Herz  4 , Udo Boeken  5 , Jens Garbade  6 , Stephan Hirt  7 , Manfred Richter  8 , Arjang Ruhpawar  9 , Jan Dieter Schmitto  10 , Felix Schönrath  11 , Rene Schramm  12 , Uwe Schulz  13 , Markus J Wilhelm  14 , Markus J Barten  15
Affiliations
Review

A Review of Induction with Rabbit Antithymocyte Globulin in Pediatric Heart Transplant Recipients

Martin Schweiger et al. Ann Transplant. .

Abstract

Pediatric heart transplantation (pHTx) represents only a small proportion of cardiac transplants. Due to these low numbers, clinical data relating to induction therapy in this special population are far less extensive than for adults. Induction is used more widely in pHTx than in adults, mainly because of early steroid withdrawal or complete steroid avoidance. Antithymocyte globulin (ATG) is the most frequent choice for induction in pHTx, and rabbit antithymocyte globulin (rATG, Thymoglobulin®) (Sanofi Genzyme) is the most widely-used ATG preparation. In the absence of large, prospective, blinded trials, we aimed to review the current literature and databases for evidence regarding the use, complications, and dosages of rATG. Analyses from registry databases suggest that, overall, ATG preparations are associated with improved graft survival compared to interleukin-2 receptor antagonists. Advantages for the use of rATG have been shown in low-risk patients given tacrolimus and mycophenolate mofetil in a steroid-free regimen, in sensitized patients with pre-formed alloantibodies and/or a positive donor-specific crossmatch, and in ABO-incompatible pHTx. Registry and clinical data have indicated no increased risk of infection or post-transplant lymphoproliferative disorder in children given rATG after pHTx. A total rATG dose in the range 3.5-7.5 mg/kg is advisable.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

Martin Schweiger has received speaker’s honoraria from Novartis and Sanofi-Genzyme. Andreas Zuckermann has received research grants from Astellas, Roche, Novartis, One Lambda, Chiesi and Sanofi, is a member of the speakers’ bureaus for Novartis, Sanofi-Genzyme, Biotest, and One Lambda, and is a member of advisory boards for Sanofi Genzyme and Sandoz and Biotest. Andres Beiras-Fernandez has received research grants from Sanofi and Orion Pharma and has received speaker’s honoraria from Sanofi Genzyme and Boehringer Ingelheim. Michael Berchtold-Herz has no conflicts of interest to declare. Udo Boeken has no conflicts of interest to declare. Jens Garbade has no conflicts of interest to declare. Stephan Hirt has no conflicts of interest to declare. Manfred Richter has received speaker’s honoraria from Novartis and Sanofi-Genzyme. Arjang Ruhpawar has no conflicts of interest to declare. Jan Dieter Schmitto has no conflicts of interest to declare. Felix Schönrath has received speaker’s honoraria from Abbott, Astra Zeneca, Bayer HealthCare, Novartis, and Sanofi-Genzyme. Rene Schramm has no conflicts of interest to declare. Uwe Schulz has received speaker’s honoraria from Sanofi-Genzyme, Novartis, and Hexal, travel grants from Biotest and Actelion, and a research grant from Actelion. Markus J. Wilhelm has received honoraria from Sanofi Genzyme. Markus J. Barten has received speaker’s honoraria from Therakos as well as honoria as a member of advisory boards for Sanofi, Novartis Pharma, and Biotest.

Figures

Figure 1
Figure 1
All-cause mortality in pediatric recipients of heart transplant during 2001–2013 who received either antithymocyte globulin (ATG) or basiliximab induction (OPTN data; Kaplan-Meier estimates) [14]. Multivariate analysis confirmed the higher mortality risk with basiliximab versus ATG induction (HR 1.27, 95% CI 1.02–1.67, p=0.030). The figure is reproduced with permission from Ansari D, Höglund P, Andersson B, Nilsson J. Comparison of basiliximab and antithymocyte globulin as induction therapy in pediatric heart transplantation: A survival analysis. J Am Heart Assoc 2015; 5(1). pii: e002790 [Available at: http://jaha.ahajournals.org/content/5/1/e002790] [16].
Figure 2
Figure 2
(A) Freedom from rejection and (B) survival in 55 pediatric heart transplant patients receiving rATG induction with tacrolimus and MMF maintenance therapy (a 2-center retrospective analysis). Rejection was defined as cellular rejection (ISHLT grade ≥2R) or antibody-mediated rejection (Kaplan-Meier estimates) [32].
Figure 3
Figure 3
Freedom from rejection in the first year after pediatric heart transplantation in 64 patients given no induction with cyclosporine/azathioprine/steroids as maintenance therapy (2005–2008) versus 39 patients given rATG induction with tacrolimus/MMF and no oral steroids as maintenance therapy (2008–2010) (a single-center retrospective analysis) (Kaplan-Meier estimates) [33].
See this image and copyright information in PMC

References

    1. Rossano JW, Dipchand AI, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Heart Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016;35(10):1185–95. - PubMed
    1. Colvin M, Smith JM, Skeans MA, et al. OPTN/SRTR 2015 Annual Data Report: Heart. Am J Transplant. 2017;7(Suppl 1):286–356. - PubMed
    1. Dipchand AI, Rossano JW, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report – 2015; Focus theme: Early graft failure. J Heart Lung Transplant. 2015;34(10):1233–43. - PubMed
    1. Hung SY, Lin TM, Chang MY, et al. Risk factors of sensitization to human leukocyte antigen in end-stage renal disease patients. Hum Immunol. 2014;75(6):531–35. - PubMed
    1. Scornik JC, Meier-KrieschE HU. Blood transfusions in organ transplant patients: Mechanisms of sensitization and implications for prevention. Am J Transplant. 2011;11(9):1785–91. - PubMed

MeSH terms