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Immunosuppressive Agents in Pediatric Heart Transplantation

  • Indira A. Khimji
  • Traci M. Kazmerski
  • Steven A. Webber
Chapter

All pediatric heart transplantation programs currently use a calcineurin inhibitor (CNI), either cyclosporine or tacrolimus, as a primary immunosuppressant. Although these drugs have much toxicity, there is insufficient data to show that CNI-free immunosuppression is safe or feasible from the time of transplantation. Most centers also use an additional adjunctive agent, either in the form of an antimetabolite (azathioprine [AZA] or mycophenolate mofetil) or, less commonly, a mammalian target of rapamycin (mTOR) inhibitor. The addition of these agents reduces early acute rejection events and may improve long-term graft and patient outcomes. The most controversial issue is whether corticosteroids should be routinely added to form a “triple therapy.” Many pediatric transplant centers have successfully used complete steroid avoidance or early steroid withdrawal. Finally, there is no agreement on whether intravenous antibody induction therapy should be routinely used. If used, there is also no agreement regarding whether it should be in the form of a monoclonal (OKT3) or polyclonal T-cell-depleting antibody (e.g., Thymoglobulin®) or an interleukin (IL)-2 receptor (IL2R) antagonist (e.g., basiliximab or daclizumab). A summary of the options for induction and maintenance therapy is shown in Table 8-1. It should be noted that there have been no large-scale randomized controlled trials of any immunosuppressive therapy in pediatric thoracic transplantation.

Keywords

Acute Rejection Mycophenolate Mofetil Heart Lung Transplant Cytokine Release Syndrome Poisoning Information 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Smith SL. Immunosuppressive therapies on organ transplantation. Organ Transplant 2002. C 2002 Medscape. http://www.medscape.com/viewarticle/437182.
  2. 2.
    Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook, 13th edition. Lexicomp, 2006–2007.Google Scholar
  3. 3.
    Pollock-Barziv SM, Dipchand AI, McCrindle BW, Nalli N, West LJ. Randomized clinical trail of tacrolimus- vs cyclosporine-based immunosuppression in pediatric heart transplantation: preliminary results at 15-month follow-up. J Heart Lung Transplant 2005; 24:190–194.PubMedCrossRefGoogle Scholar
  4. 4.
    Kobashigawa J, Miller LW, Russell SD, et al. Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report. Am J Transplant 2006; 6:1377–1386.PubMedCrossRefGoogle Scholar
  5. 5.
    English RF, Pophal SA, Bacanu S, Fricker FJ, Boyle GJ, Miller SA, Law Y, Ellis D, Harker K, Sutton R, Pigula F, Webber SA. Long-term comparison of tacrolimus and cyclosporine induced nephrotoxicity in pediatric heart transplant recipients. Am J Transplant 2002; 2:769–773.PubMedCrossRefGoogle Scholar
  6. 6.
    Robinson BV, Boyle GJ, Miller SA, Law Y, Griffith BP, Webber SA. Optimal dosing of intravenous tacrolimus following pediatric heart transplantation. J Heart Lung Transplant 1999; 18:786–791.PubMedCrossRefGoogle Scholar
  7. 7.
    Boucek MM, Edwards LB, Keck BM, Trulock EP, Taylor DO, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: eighth official pediatric report—2005. J Heart Lung Transplant 2005; 24:968–982.PubMedCrossRefGoogle Scholar
  8. 8.
    Eisen HJ, Kobashigawa J, Keogh A, et al. Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. J Heart Lung Transplant 2005; 24:517–525.PubMedCrossRefGoogle Scholar
  9. 9.
    Webber SA, McCurry K, Zeevi A. Heart and lung transplantation in children. Lancet 2006; 368: 53–69.PubMedCrossRefGoogle Scholar
  10. 10.
    Ortho Biotech Products, L.P. Orthoclone OKT3® Package Insert. November 2004.Google Scholar
  11. 11.
    Hooks M, Wade C, Millikan WJ. Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. Pharmacotherapy 1991; 11(1): 26–37.PubMedGoogle Scholar
  12. 12.
    Wilde M, Goa K. Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs 1996; 51(5): 865–894.PubMedCrossRefGoogle Scholar
  13. 13.
    Pittock S, Rabinstein A, Edwards B, Wijdicks E. OKT3 neurotoxicity presenting as akinetic mutism. Transplantation 2003; 75(7):1058–1060.PubMedCrossRefGoogle Scholar
  14. 14.
    Genzyme Corporation. Campath® Package Insert. July 2005.Google Scholar
  15. 15.
    Ford KA, Cale CM, Rees PG, Elliott MJ, Burch M. Initial data on basiliximab in critically ill children undergoing heart transplantation. J Heart Lung Transplant 2005; 24:1284–1288.PubMedCrossRefGoogle Scholar
  16. 16.
    Smith J, Nemeth T, McDonald R. Current immunosuppressive agents: efficacy, side effects, and utilization. Pediatr Clin N Am 2003; 50:1283–1300.CrossRefGoogle Scholar
  17. 17.
    Kobashigawa J, David K, Morris J, et al. Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids. Transplant Proc 2005; 37:1333–1339.PubMedCrossRefGoogle Scholar
  18. 18.
    Chin C, Pittson S, Luikart H, et al. Induction therapy for pediatric and adult heart transplantation: comparison between OKT3 and daclizumab. Transplantation 2005; 80:477–481.PubMedCrossRefGoogle Scholar
  19. 19.
    Hoffman-La Roche Inc. Zenapax® Package Insert. September 2005.Google Scholar

Copyright information

© Springer-Verlag London Limited 2008

Authors and Affiliations

  • Indira A. Khimji
    • 1
  • Traci M. Kazmerski
    • 2
  • Steven A. Webber
    • 3
  1. 1.Pharmacy DepartmentChildren's Hospital of PittsburghPittsburghUSA
  2. 2.Cardiac Intensive Care UnitChildren's Hospital of PittsburghPittsburghUSA
  3. 3.Department of PediatricsUniversity of Pittsburgh School of MedicinePittsburghUSA

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