Pediatric heart transplantation: Immunosuppression and its complications

Current Opinion in Cardiology

Volumn 19, Issue 2, 2004, Pages 104-109

  Russo, Linda M ^a   Webber, Steven A ^a  

^a CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

Author keywords

Genetic polymorphisms; Heart transplantation; Immunosuppression; Pediatrics; Pharmacogenomics

Indexed keywords

BASILIXIMAB; CALCINEURIN INHIBITOR; CORTICOSTEROID; CYCLOSPORIN A; DACLIZUMAB; IMMUNOSUPPRESSIVE AGENT; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; TACROLIMUS; THYMOCYTE ANTIBODY;

BONE DISEASE; CHILD; DRUG DISPOSITION; DRUG EFFICACY; HEART TRANSPLANTATION; HUMAN; HYPERLIPIDEMIA; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY DYSFUNCTION; KIDNEY FAILURE; MYALGIA; NEPHROTOXICITY; PRIORITY JOURNAL; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT; SPINE FRACTURE; TREATMENT OUTCOME;

ADULT; CHILD; CYTOKINES; DRUG RESISTANCE, MULTIPLE; GENES, MDR; GRAFT REJECTION; HEART DISEASES; HEART TRANSPLANTATION; HUMANS; IMMUNE TOLERANCE; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; LYMPHATIC IRRADIATION; POLYMORPHISM, GENETIC; TREATMENT OUTCOME;

EID: 1642394990     PISSN: 02684705     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001573-200403000-00006     Document Type: Review

References (21)

1. Boucek MM, Edwards LB, Keck BM, et al.: The Registry of the International Society for Heart and Lung Transplantation: Sixth Official Pediatric Report-2003. J Heart Lung Transplant 2003, 22:636-652. This annual report is now providing important information on trends in use and major morbidities of current immunosuppressive therapies in children.
2. Webber SA: The current state of, and future prospects for, cardiac transplantation in children. Cardiol Young 2003, 13:64-83. This comprehensive review of the current state of pediatric heart transplantation places emphasis on current immunosuppressive strategies and their efficacy and morbidities. The importance of taking tolerance trials to the clinic is emphasized.
3. Reddy SC, Laughlin K, Webber SA: Immunosuppression in pediatric heart transplantation: 2003 and beyond. Curr Treat Options Cardiovasc Med 2003, 5:417-428. This is a systematic review of current immunosuppressive agents, with pediatric doses, side effects, and relative cost.
4. Parisi F, Danesi H, Squitieri C, et al.: Thymoglobulin use in pediatric heart transplantation. J Heart Lung Transplant 2003, 22:591-593. This report from Rome describes experience with Thymoglobulin induction in 31 cyclosporine-treated pediatric heart recipients and shows that excellent results can be achieved with this combination.
5. DiFilippo S, Boissannat P, Sassolas F, et al.: Rabbit antithymocyte globulin as induction immunotherapy in pediatric heart transplantation. Transplantation 2003, 75:354-358. This report, like the one from the Rome group, describes excellent medium-term results using Thymoglobulin induction in combination with a cyclosporine-based immunosuppressive regimen.
6. Razzouk AJ, Chinnock RE, Gundry SR, et al.: Transplantation as a primary treatment for hypoplastic left heart syndrome: Intermediate-term results. Ann Thorac Surg 1996, 62:1-7.
7. Canter CE, Moorhead S, Saffitz JE, et al.: Steroid withdrawal in the pediatric heart transplant recipient initially treated with triple immunosuppression. J Heart Lung Transplant 1994, 13:74-80.
8. Leonard H, Hornung T, Parry G, Dark JH: Pediatric cardiac transplant: Results using a steroid-free maintenance regimen. Pediatr Transpl 2003, 7:59-63. This is a further report that demonstrates that steroid-free maintenance immunosuppression is feasible in most pediatric recipients, even if managed with cyclosporine-based therapy. However, the potential burden on long-term renal function is emphasized.
9. Asano M, Gundry SR, Razzouk AJ, et al.: Total lymphoid irradiation for refractory rejection in pediatric heart transplantation. Ann Thorac Surg 2002, 74:1979-1985. This study reports experience of TLI in 11 children with refractory rejection. TLI was an effective adjunct for reversal of rejection, but this group experienced a high relative risk of late posttransplantation lymphoproliferative disorders and graft vasculopathy.
10. Chin C, Hunt S, Robbins R, et al.: Long-term follow-up after total lymphoid irradiation in pediatric heart transplant recipients. J Heart Lung Transplant 2002, 21:667-673.
11. Webber SA, Naftel DC, Parker J, et al.: Late rejection episodes greater than 1 year after pediatric heart transplantation: risk factors and outcomes. J Heart Lung Transplant 2003, 22:869-875. This large study from the Pediatric Heart Transplant Study group analyzes risk factors and outcomes for late acute rejection episodes among patients at 18 pediatric heart transplantation centers. One-fourth of patients experienced late rejection episodes. Black race, older age at transplantation, and adverse first-year rejection history were the principal risk factors for late rejection. Freedom from late rejection was associated with extremely low risk of late death, whereas one-fourth of children experiencing late rejection died during long-term follow-up.
12. Kuhn MA, Deming DD, Cephus CE, et al.: Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients. J Heart Lung Transplant 2003, 22:276-280. This study supports prior observations that routine surveillance biopsies are associated with important incidence of moderate acute rejection (8%-10% at as long as 10 years post-transplantation in this study).
13. Wagner K, Oliver MC, Boyle GJ, et al.: Endomyocardial biopsy in pediatric heart transplant recipients: a useful exercise? (Analysis of 1169 biopsies). Pediatr Transpl 2000, 4:186-192.
14. Morrow WR, Chinnock RE: Survival after heart transplantation. In Pediatric Solid Organ Transplantation. Edited by Tejani AH, Harmon WE, Fine RN. Copenhagen: Munksgaard, 2000:417-426.
15. Awad MR, Webber SA, Boyle GJ, et al.: The effect of cytokine gene polymorphism on pediatric heart allograft outcome. J Heart Lung Transplant 2001, 20:625-630.
16. Zheng HX, Webber SA, Zeevi A, et al.: The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients. Hum Immunol 2002, 63:765-770. This is the first report to show that polymorphisms of the gene encoding P-glycoprotein influence the ability to wean patients off corticosteroids after solid organ transplantation.
17. Zheng H, Webber S, Zeevi A, et al.: Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms. Am J Transplant 2003, 3:477-483. This report demonstrates that polymorphisms among genes involved in immunosuppressive drug disposition and metabolism are important determinants of tacrolimus dose requirements in pediatric patients. These observations may, in part, explain the higher dose requirements for many immunosuppressive agents among black transplant recipients.
18. English RF, Pophal SA, Bacanu S, et al.: Long-term comparison of tacrolimus and cyclosporine induced nephrotoxicity in pediatric heart transplant recipients. Am J Transplant 2002, 2:769-773. This is the first very long-term follow-up study comparing the nephrotoxicity of cyclosporine-and tacrolimus-treated heart transplant recipients. No differences in long-term nephrotoxicity were observed between the groups. Calculated creatinine clearance was found to consistently overestimate measured glomerular filtration rate.
19. Rice JE, Shipp AT, Carlin JB, et al.: Late reduction in cyclosporine dosage does not improve renal function in pediatric heart transplant recipients. J Heart Lung Transplant 2002, 21:1109-1112.
20. Daniels MW, Wilson DM, Paguntalan HG, et al.: Bone mineral density in pediatric transplant recipients. Transplantation 2003, 76:673-678. This report focuses on a very important, but all too neglected, adverse effect of chronic immunosuppressive therapy. Cardiac transplant recipients had significantly reduced bone mineral density Z scores at all skeletal sites that were studied.
21. Chin C, Gamberg P, Miller J, et al.: Efficacy and safety of atorvastatin after pediatric heart transplantation. J Heart Lung Transplant 2002, 21:1213-1217. Atorvastatin appears effective at lowering total cholesterol, triglycerides, and low-density lipoprotein in pediatric heart recipients but is associated with an important prevalence of muscle pain, creatine phosphokinase elevation, and rhabdomyolysis.