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Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies

Published online by Cambridge University Press:  13 December 2011

Alfred Asante-Korang*
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
Jeffrey P. Jacobs
Affiliation:
Division of Cardiothoracic Surgery, All Children's Hospital, Saint Petersburg, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
Jeremy Ringewald
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Jennifer Carapellucci
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Kristin Rosenberg
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Daniel McKenna
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Jorge McCormack
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
Ivan Wilmot
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Abigail Gjeldum
Affiliation:
Division of Cardiology, All Children's Hospital, Saint Petersburg, United States of America
Mayra Lopez-Cepero
Affiliation:
LifeLink Immunology Lab, LifeLink Foundation, Tampa, United States of America
John Sleasman
Affiliation:
Department of Immunology, All Children's Hospital, Saint Petersburg, Florida, United States of America University of South Florida (USF), Saint Petersburg and Tampa, Florida, United States of America
*
Correspondence to: Alfred Asante-Korang, MB CHB, MRCP, Clinical Associate Professor of Pediatrics, University of South Florida College of Medicine, Pediatric Cardiology Associates, 601 5th Street South, Suite 711, Saint Petersburg, Florida, 33701, United States of America. Tel: 727-322-4852; Fax: 727-821-2461; E-mail: ak111322@aol.com

Abstract

Highly sensitised children in need of cardiac transplantation have overall poor outcomes because of increased risk for dysfunction of the cardiac allograft, acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac allograft. Cardiopulmonary bypass and the frequent use of blood products in the operating room and cardiac intensive care unit, as well as the frequent use of homografts, have predisposed potential recipients of transplants to allosensitisation. The expansion in the use of ventricular assist devices and extracorporeal membrane oxygenation has also contributed to increasing rates of allosensitisation in candidates for cardiac transplantation. Antibodies to Human Leukocyte Antigen can be detected before transplantation using several different techniques, the most common being the “complement-dependent lymphocytotoxicity assays”. “Solid-phase assays”, particularly the “Luminex® single antigen bead method”, offer improved specificity and more detailed information regarding specificities of antibodies, leading to improved matching of donors with recipients. Allosensitisation prolongs the time on the waiting list for potential recipients of transplantation and increases the risk of complications and death after transplantation. Aggressive reduction of antibodies to Human Leukocyte Antigen in these high-risk patients is therefore of vital importance for long-term survival of the patient and cardiac allograft. Strategies to decrease Panel Reactive Antibody or percent reactive antibody before transplantation include plasmapheresis, intravenous administration of immunoglobulin, and specific treatment to reduce B-cells, particularly Rituximab. These strategies have resulted in varying degrees of success. Antibody-mediated rejection and cardiac allograft vasculopathy are two of the most important complications of transplantation in patients with high Panel Reactive Antibody. The treatment of antibody-mediated rejection in recipients of cardiac transplants is largely empirical and includes the use of high-dose corticosteroids, plasmapheresis, intravenous administration of immunoglobulins, anti-thymocyte globulin, and Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic complement-mediated endothelial injury and chronic vascular rejection. The use of proliferation signal inhibitors, such as sirolimus and everolimus, has been shown to delay the progression of cardiac allograft vasculopathy. In some non-sensitised recipients of cardiac transplants, the de novo formation of antibodies to Human Leukocyte Antigen after transplantation may increase the likelihood of adverse clinical outcomes. The use of serial testing for donor-specific antibodies after cardiac transplantation may be advisable in patients with frequent episodes of rejection and patients with history of sensitisation. Allosensitisation before transplantation can negatively influence outcomes after transplantation. A high incidence of antibody-mediated rejection and graft vasculopathy can result in graft failure and decreased survival. Current strategies to decrease allosensitisation have helped to expand the pool of donors, improve times on the waiting list, and decrease mortality. Centres of transplantation offering desensitisation are currently using plasmapheresis to remove circulating antibodies; intravenous immunoglobulin to inactivate antibodies; cyclophosphamide to suppress B-cell proliferation; and Rituximab to deplete B-lymphocytes. Similar approaches are also used to treat antibody-mediated rejection after transplantation with promising results.

Type
Original Article
Copyright
Copyright © Cambridge University Press 2011

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References

1.Taylor, DO, Edwards, LB, Boucek, MM, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult heart transplant report – 2007. J Heart Lung Transplant 2007; 26: 769781.CrossRefGoogle ScholarPubMed
2.Velez, M, Johnson, MR. Management of allosensitized cardiac transplant candidates. Transplant Rev (Orlando) 2009; 23: 235247.CrossRefGoogle ScholarPubMed
3.Itescu, S, Schuster, M, Burke, E, et al. Immunologic consequences of assist devices. Cardiol Clin 2003; 21: 119133.CrossRefGoogle Scholar
4.Eckman, PM. Immunosuppression in the sentisized heart transplant recipient. Curr Opin Organ Transplant 2010; 15: 650656.CrossRefGoogle Scholar
5.Jacobs, JP, Quintessenza, JA, Boucek, RJ, et al. Pediatric cardiac transplantation in children with high panel reactive antibody. Ann Thorac Surg 2004; 78: 17031709.CrossRefGoogle ScholarPubMed
6.Kobashigawa, JA, Sabad, A, Drinkwater, D, et al. Pretransplant panel reactive-antibody screens. Are they truly a marker for poor outcome after cardiac transplantation? Circulation 1996; 94 (9 Suppl): II294II297.Google ScholarPubMed
7.Nwakanma, LU, Williams, JA, Weiss, ES, Russell, SD, Baumgarter, WA, Conte, JV. Influence of pre-transplant panel-reactive antibody on outcomes in 8,160 heart transplant recipients in recent era. Ann Thorac Surg 2007; 84: 15561562; discussion 62-63.CrossRefGoogle Scholar
8.Ballew, CC, Bergin, JD. Management of patients with preformed reactive antibodies who are awaiting cardiac transplantation. Am J Crit Care 2005; 14: 4651.Google ScholarPubMed
9.Schuster, M, Kocher, A, John, R, et al. B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression. Hum Immunol 2002; 63: 211220.CrossRefGoogle ScholarPubMed
10.Drakos, SG, Stringham, JC, Long, JW, et al. Prevalence and risks of allosensitization in HeartMate left ventricular assist device recipients: the impact of leukofiltered cellular blood product transfusions. J Thorac Cardiovasc Surg 2007; 133: 16121619.CrossRefGoogle ScholarPubMed
11.Joyce, DL, Southard, RE, Torre-Amione, G, Noon, GP, Land, GA, Loebe, M. Impact of left ventricular assist device-mediated humoral sensitization on post-transplant outcomes. J Heart Lung Transplant 2005; 24: 20542059.CrossRefGoogle Scholar
12.Baran, DA, Gass, AL, Galin, ID, et al. Lack of sensitization and equivalent post-transplant outcomes with the Novacor left ventricular assist device. J Heart Lung Transplant 2005; 24: 18861890.CrossRefGoogle ScholarPubMed
13.Nikaein, A, Cherikh, W, Nelson, K, et al. Organ procurement and transplantation network/united network of organ sharing histocompatibility committee collaborative study to evaluate prediction of crossmatch results in highly sensitized patients. Transplantation 2009; 87: 557562.CrossRefGoogle ScholarPubMed
14.Rhee, JK, McGee, E, Subacius, H, et al. The impact of virtual crossmatch on cardiac allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant 2010; 29: S153.CrossRefGoogle Scholar
15.Pisani, BA, Mullen, GM, Malinowska, K, et al. Plasmapheresis with intravenous immunoglobulin G is effective in patients with elevated panel reactive antibody prior to cardiac transplantation. J Heart Lung Transplant 1999; 18: 701706.CrossRefGoogle Scholar
16.Leech, SH, Lopez-Cepero, M, LeFor, WM, et al. Management of the sensitized cardiac recipient: the use of plasmapheresis and intravenous immunoglobulin. Clin Transplant 2006; 20: 476484.CrossRefGoogle ScholarPubMed
17.John, R, Lietz, K, Burke, E, et al. Intravenous immunoglobulin reduces anti-Human Leukocyte Antigen alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients. Circulation 1999; 100: II229II235.CrossRefGoogle Scholar
18.Itescu, S, Burke, E, Lietz, K, et al. Intravenous pulse administration of Cyclophosphamide is an effective and safe treatment for sensitized cardiac allograft recipients. Circulation 2002; 105: 12141219.CrossRefGoogle ScholarPubMed
19.Balfour, IC, Fiore, A, Graff, RJ, Knutsen, AP. Use of Rituximab to decrease panel-reactive antibodies. J Heart Lung Transplant 2005; 24: 628630.CrossRefGoogle ScholarPubMed
20.Becker, YT, Samaniego-Picota, M, Sollinger, HW. The emerging role of Rituximab in organ transplantation. Transpl Int 2006; 19: 621628.CrossRefGoogle ScholarPubMed
21.Sidner, RA, Book, BK, Agarwal, A, Bearden, CM, Vieira, CA, Pescovitz, MD. In vivo human B-cell subset recovery after in vivo depletion with Rituximab, anti-human CD20 monoclonal antibody. Hum Antibodies 2004; 13: 5562.CrossRefGoogle Scholar
22.Teuteberg, JJ, Shullo, MA, Zomak, R, et al. Alemtuzumab induction prior to cardiac transplantation with lower intensity immunosuppression: one year outcomes. Am J Transplant 2010; 10: 382388.CrossRefGoogle ScholarPubMed
23.Lick, SD, Vaidya, S, Kollar, AC, et al. Peri-operative alemtuzumab (campath-1H) and plasmapheresis for high Panel Reactive Antibody positive lymphocyte crossmatch heart transplant: a strategy to shorten LVAD support. J Heart Lung Transplant 2008; 27: 10361039.CrossRefGoogle Scholar
24.Trivedi, HL, Terasaki, PI, Feroz, A, et al. Abrogation of anti-HLA antibodies via proteasome inhibition. Transplantation 2009; 87: 15551561.CrossRefGoogle ScholarPubMed
25.Patel, J, Kittelson, M, Reed, E, et al. The effectiveness of a standardized desensitization protocol in reducing calculated panel reactive antibodies in sensitized heart transplant candidates: does it make sense to desensitize? J Heart Lung Transplant 2010; 29: S103.CrossRefGoogle Scholar
26.Holt, DB, Lublin, DM, Phelan, DL, et al. Mortality and morbidity in pre-sensitized pediatric heart transplant recipients with a positive donor crossmatch utilizing peri-operative plasmapheresis and cytolytic therapy. J Heart Lung Transplant 2007; 26: 876882.CrossRefGoogle ScholarPubMed
27.Wright, EJ, Fiser, WP, Edens, RE, et al. Cardiac transplant outcomes in pediatric patients with pre-formed anti-HLA antibodies and/or positive retrospective crossmatch. J Heart Lung Transplant 2007; 26: 11631169.CrossRefGoogle ScholarPubMed
28.Pollock-BarZiv, SM, den Hollander, N, Ngan, BY, et al. Pediatric heart transplantation in HLA sensitized patients: evolving management and assessment of intermediate-term outcomes in a high-risk population. Circulation 2007; 116 (1 Suppl): I-172I-178.CrossRefGoogle Scholar
29.Rossano, JW, Morales, DLS, Zafar, F, et al. Impact of human leukocyte antigens on long-term outcome in pediatric heart transplant patients: an analysis of the United Network of Organ Sharing Database. J Thorac Cardiovasc Surg 2010; 140: 694699.CrossRefGoogle ScholarPubMed
30.Reed, EF, Demetris, AJ, Hammond, E, et al. Acute antibody mediated rejection of cardiac transplants. J Heart Lung Transplant 2006; 25: 153159.CrossRefGoogle ScholarPubMed
31.Michaels, PJ, Espejo, ML, Kobashigawa, J, et al. Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant 2003; 22: 5869.CrossRefGoogle ScholarPubMed
32.Smith, RN, Brousaides, N, Grazette, L, et al. C4d deposition in cardiac allografts correlates with alloantibody. J Heart Lung Transplant 2005; 24: 12021210.CrossRefGoogle ScholarPubMed
33.Rodriguez, ER, Skojec, DV, Tan, CD, et al. Antibody-mediated rejection in human cardiac allografts: evaluation of immunoglobulins and complement activation products C4d and C3d as markers. Am J Transplant 2005; 5: 27782785.CrossRefGoogle ScholarPubMed
34.Di Filippo, S, Gimita, A, Webber, SA, et al. Impact of ELISA-detected anti-HLA antibodies on pediatric cardiac allograft outcome. Hum Immunol 2005; 66: 513518.CrossRefGoogle ScholarPubMed
35.Jacobs, JP, Asante-Korang, A, O'Brien, SM, et al. Lessons learned from 119 consecutive cardiac transplants for pediatric and congenital heart disease. Ann Thorac Surg 2011; 91: 12481255; PMID:21440154, April, 2011.CrossRefGoogle ScholarPubMed
36.Garrett, HE Jr, Duvall-Seaman, D, Helsley, B, Groshart, K. Treatment of vascular rejection with Rituximab in cardiac transplantation. J Heart Lung Transplant 2005; 24: 13371342.CrossRefGoogle ScholarPubMed
37.Girnita, AL, Webber, SA, Zeevi, A. Anti-HLA antibodies in pediatric solid organ transplantation. Pediatr Transplant 2006; 10: 146153.CrossRefGoogle ScholarPubMed
38.Taylor, DO, Yowell, RL, Kfoury, AG, Hammond, EH, Renlund, DG. Allograft coronary artery disease: clinical correlations with circulating anti-HLA antibodies and the immunohistopathologic pattern of vascular rejection. J Heart Lung Transplant 2000; 19: 518521.CrossRefGoogle ScholarPubMed
39.Soleimani, B, Lechler, RI, Hornick, PI, George, AJ. Role of alloantibodies in the pathogenesis of graft arteriosclerosis in cardiac transplantation. Am J Transplant 2006; 6: 17811785.CrossRefGoogle ScholarPubMed
40.Mancini, D, Pinney, S, Burkhoff, D, et al. Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation 2003; 108: 4853.CrossRefGoogle ScholarPubMed
41.Keogh, A, Richardson, M, Ruygrok, P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation 2004; 110: 26942700.CrossRefGoogle ScholarPubMed
42.Eisen, HJ, Tuzcu, EM, Dorent, R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003; 349: 847858.CrossRefGoogle ScholarPubMed
43.Costanzo, MR, Dipchand, A, Starling, R, et al. The ISHLT Guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010; 29: 914956.CrossRefGoogle Scholar
44.Kobashigawa, J, Mehra, M, West, L, et al. Report from a consensus conference on the sensitized patient awaiting heart transplantation. J Heart Lung Transplant 2009; 28: 213225.CrossRefGoogle ScholarPubMed
45.Tambur, AR, Pamboukian, SV, Costanzo, MR, et al. The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. Transplantation 2005; 80: 10191025.CrossRefGoogle ScholarPubMed
46.Xydas, S, Yang, JK, Burke, EM, et al. Utility of post-transplant anti-HLA antibody measurements in pediatric cardiac transplant recipients. J Heart Lung Transplant 2005; 24: 12891296.CrossRefGoogle ScholarPubMed
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