Immunosuppression and adult heart transplantation: emerging therapies and opportunities

References

• Mozzafarian D, Benjamin EJ, Go AS, et al.; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–e360.
   PubMed Web of Science ®Google Scholar
• Khavjou O, Konstam MA, Maddox TM, et al.; On behalf of the American Heart Association Advocacy Coordinating Committee; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Stroke Council. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606–619.
   PubMed Web of Science ®Google Scholar
• Yancy CY, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2013;68(13):1476–1488.
   Web of Science ®Google Scholar
• Costanzo MR, Mills RM, Wynne J. Characteristics of “Stage D” heart failure: insights from the acute decompensated heart failure national registry longitudinal module (ADHERE LM). Am Heart J. 2008;155(2):339–347.
   PubMed Web of Science ®Google Scholar
• Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435–1443.
   PubMed Web of Science ®Google Scholar
• Kirklin JK, Naftel DC, Pagani FD, et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant. 2015;34(12):1495–1504.
   PubMed Web of Science ®Google Scholar
• Lund LH, Edwards LB, Kucheryavaya AY, et al. The registry of the international society for heart and lung transplantation: thirty-second official adult heart transplantation report–2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34(10):1244–1254.
   PubMed Web of Science ®Google Scholar
• Wood KJ, Bushell A, Hester J. Regulatory immune cells in transplantation. Nat Rev Immunol. 2012;12:417–430.
   PubMed Web of Science ®Google Scholar
• Berry GJ, Burke MM, Andersen C, et al. The 2013 International Society for Heart and Lung Transplantation working formulation for the standarization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013;32:1147–1162.
   PubMed Web of Science ®Google Scholar
• Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27(1):591–619.
   PubMed Web of Science ®Google Scholar
• Turka LA, Linsley PS, Lin H, et al. T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo. Proc Natl Acad Sci. 1992;89(22):11102–11105.
   PubMed Web of Science ®Google Scholar
• Lindenfeld J, Miller GG, Shakar SF, et al. Drug therapy in the heart transplant recipient: part II: immunosuppressive drugs. Circulation. 2004;110(25):3858–3865.
   PubMed Web of Science ®Google Scholar
• Nwakanma LU, Williams JA, Weiss ES, et al. Influence of pretransplant panel-reactive antibody on outcomes in 8,160 heart transplant recipients in the recent era. Ann Thorac Surg. 2007;84(5):1556–1563.
   PubMed Web of Science ®Google Scholar
• Stastny P, Salvador I-M, Lavingia B. Evaluation of the highly sensitized transplant recipient. Pediatr Nephrol. 2011;26(11):1927–1935.
   PubMed Web of Science ®Google Scholar
• Wood KJ, Goto R. Mechanisms of rejection: current perspectives. Transplantation. 2012;93(1):1–10.
   PubMed Web of Science ®Google Scholar
• Cecka JM. Calculated PRA (CPRA): the new measure of sensitization for transplant candidates. Am J Transplant. 2010;10(1):26–29.
   PubMed Web of Science ®Google Scholar
• Stehlik J, Islam N, Hurst D, et al. Utility of virtual crossmatch in sensitized patients awaiting heart transplantation. J Heart Lung Transplant. 2009;28(11):1129–1134.
   PubMed Web of Science ®Google Scholar
• Tinckam KJ, Chandraker A. Mechanisms and role of HLA and non-HLA alloantibodies. Clin J Am Soc Nephrol. 2006;1(3):404–414.
   PubMed Web of Science ®Google Scholar
• Chih S, Patel J. Desensitization strategies in adult heart transplantation-Will persistence pay off? J Heart Lung Transplant. 2016;35(8):962–972.
   PubMed Web of Science ®Google Scholar
• 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(3):213–225.
   PubMedGoogle Scholar
• Higgins R, Kirklin JK, Brown RN, et al. To induced or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy? J Heart Lung Transplant. 2005;24:392–400.
   PubMed Web of Science ®Google Scholar
• Emin A, Rogers CA, Thekkudan J, et al. Antithymocyte globulin induction therapy for adult heart transplantation: a UK national study. J Heart Lungtransplant. 2001;30(7):770–777.
   Web of Science ®Google Scholar
• Teuteberg JJ, Shullo MA, Zomak R, et al. Alemtuzumab induction prior to cardiac transplantation with lower intensity maintenance immunosuppression: one-year outcomes. Am J Transplant. 2010;10(2):382–388.
   PubMed Web of Science ®Google Scholar
• Morris PJ, Russell NK. Alemtuzumab (Campath-1H): a systematic review in organ transplantation. Transplantation. 2006;81:1361–1367.
   PubMed Web of Science ®Google Scholar
• Hao W-J, Zong H-T, Cui Y-S, et al. The efficacy and safety of alemtuzumab and daclizumab versus antithymocyte globulin during organ transplantation: a meta analysis. Transplant Proc. 2012;44(10):2955–2960.
   PubMed Web of Science ®Google Scholar
• Mehra MR, Zucker MJ, Wagoner L, et al. A multicenter, prospective, randomized, double-blind trial of basiliximab in heart transplantation. J Heart Lung Transplant. 2005;24:1297–1304.
   PubMed Web of Science ®Google Scholar
• Hershberger RE, Starling RC, Eisen HJ, et al. Daclizumab to prevent rejection after cardiac transplantation. N Engl J Med. 2005;352:2705–2713.
   PubMed Web of Science ®Google Scholar
• Zhang R, Haverich A, Strüber M, et al. Delayed onset of cardiac allograft vasculopathy by induction therapy using anti-thymocyte globulin. J Heart Lung Transplant. 2008;27(6):603–609.
   PubMed Web of Science ®Google Scholar
• Opelz G, Döhler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(2):222–230.
   PubMed Web of Science ®Google Scholar
• Penninga L, Møller CH, Gustafsson F, et al. Immunosuppressive T-cell antibody induction for heart transplant recipients. Cochrane Database Syst Rev. 2013. DOI:10.1002/14651858.CD008842.pub2
   Web of Science ®Google Scholar
• Chandraker A, Kobashigawa JA, Stehlik J, et al. Rituximab induction in cardiac transplantation is associated with accelerated coronary artery vasculopathy: CTOT11. [abstract]. Am J Transplant. 2016;16(suppl 3):403.
   Google Scholar
• Baran DA, Zucker MJ, Arroyo LH, et al. A prospective, randomized trial of single drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial. Circ Heart Fail. 2011;4(2):129–137.
   PubMed Web of Science ®Google Scholar
• Kobashigawa JA. Strategies in immunosuppression after heart transplantation: is less better? Circ Heart Fail. 2011;4(2):111–113.
   PubMed Web of Science ®Google Scholar
• Kobashigawa J, Miller L, Renlund D, et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Transplantation. 1998;66(4):507–515.
   PubMed Web of Science ®Google Scholar
• Taylor DO, Barr ML, Radovancevic B, et al. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus. J Heart Lung Transplant. 1999;18(4):336–345.
   PubMed Web of Science ®Google Scholar
• Kobashigawa JA, 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(6):1377–1386.
   PubMed Web of Science ®Google Scholar
• Costanzo MR, Dipchand A, Starling R, et al. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914–956.
   PubMed Web of Science ®Google Scholar
• Ho EK, Vlad G, Vasilescu ER, et al. Pre- and posttransplantation allosensitization in heart allograft recipients: major impact of de novo alloantibody production on allograft survival. Hum Immunol. 2011;72(1):5–10.
   PubMed Web of Science ®Google Scholar
• Smith JD, Banner NR, Hamour IM, et al. De novo donor HLA-specific antibodies after heart transplantation are an independent predictor of poor patient survival. Am J Transplant. 2011;11(2):312–319.
   PubMed Web of Science ®Google Scholar
• Kfoury A, Hammond M, Snow G, et al. Cardiovascular mortality among heart transplant recipients with asymptomatic antibody-mediated or stable mixed cellularand antibody-mediated rejeciton. J Heart Lung Transplant. 2008;29:781–784.
   Google Scholar
• Colvin MM, Cook JL, Chang P, et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015;131:1608–1639.
   PubMed Web of Science ®Google Scholar
• Nair N, Ball T, Uber PA, et al. Current and future challenges in therapy for antibody-mediated rejection. J Heart Lung Transplant. 2011;30:612–617.
   PubMed Web of Science ®Google Scholar
• Michaels P, Espejo M, Kobashigawa JA, et al. Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant. 2003;22:58–69.
   PubMed Web of Science ®Google Scholar
• Taylor D, Meiser B, Webber S, et al. Task force 2: immunosuppression and rejection. The International Society of Heart and Lung Transplant guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29:926–933.
   Web of Science ®Google Scholar
• Grauhan O, Knosalla C, Ewert R, et al. Plasmapheresis and cyclophosphamide in the treatment of humoral rejection after heart transplantation. J Heart Lung Transplant. 2001;20:316–321.
   PubMed Web of Science ®Google Scholar
• Gelfand EW. Antibody-directed therapy: past, present, and future. J Allerg Clin Immunol. 2001;108(suppl):S111–S116.
   PubMed Web of Science ®Google Scholar
• Jordan SC, Quartel AW, Czer LS, et al. Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action. Transplantation. 1998;66:800–805.
   PubMed Web of Science ®Google Scholar
• Marques M, Schwartz J. Update on extracorporeal photopheresis in heart and lung transplantation. J Clin Apher. 2001;26:146–151.
   Web of Science ®Google Scholar
• Barr ML, Meiser BM, Eisen HJ, et al. Photopheresis for the prevention of rejection in cardiac transplantation. N Engl J Med. 1998;339(24):1744–1751.
   PubMed Web of Science ®Google Scholar
• Almuti HE Jr, Duvall-Seaman D, Helsley B, et al. Treatment of vascular rejection with rituximab in cardiac transplantation. J Heart Lung Transplant. 2005;24:1337–1342.
   PubMed Web of Science ®Google Scholar
• Woodside KJ, Lick SD. Alemtuzumab (Campath 1H) as successful salvage therapy for recurrent steroid-resistant heart transplant recipient. J Heart Lung Transplant. 2007;26:750–752.
   PubMed Web of Science ®Google Scholar
• Patel J, Everly M, Chang D, et al. Reduction of alloantibodies via proteasome inhibition in cardiac transplantation. J Heart Lung Transplant. 2011;30(12):1320–1326.
   PubMed Web of Science ®Google Scholar
• Perry DK, Burns JM, Pollinger HS, et al. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant. 2009;9:201–209.
   PubMed Web of Science ®Google Scholar
• Everly MJ, Everly JJ, Susskind B, et al. Bortezomib provides effective therapy for antibody-mediated and cell-mediated acute rejection. Transplantation. 2008;86:1754–1761.
   PubMed Web of Science ®Google Scholar
• Stegall M, Diwan T, Raghavaiah S, et al. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant. 2011;11:2405–2413.
   PubMed Web of Science ®Google Scholar
• The De-novo use of eculizumab alongside conventional maintenance therapy in presensitized patients receiving cardiac transplantation: an, open-label, investigator initiated pilot trial: [the DUET cardiac trial]. clinicaltrials.gov NCT02013037.
   Google Scholar
• Orandi BJ, Alackar N, Kraus ES, et al. Presentation and outcomes of C4d negative antibody-mediated rejection after kidney transplantation. Am J Transplant. 2016;16(1):213–220.
   PubMed Web of Science ®Google Scholar
• Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med. 1995;333(10):621–627.
   PubMed Web of Science ®Google Scholar
• Fang JC, Kinlay S, Beltrame J, et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomized trial. Lancet. 2002;359(9312):1108–1113.
   PubMed Web of Science ®Google Scholar
• Patel J, Kittleson M, Czer L, et al. Does ACE inhibitor use in heart transplantation decrease the development of cardiac allograft vasculopathy? J Heart and Lung Transplant [Abstract]. 2016;35(4S):S198.
   Google Scholar
• Kobayashi Y, Okada K, Khush K, et al. Angiotensin-converting enzyme inhibition early after cardiac transplantation: a multi-center, randomized, double-blind trial comparing ramipril versus placebo. J Am Coll Cardiol. 2016;67(13S):1445–1445.
   Google Scholar
• Kobashigawa JA, Tobis JM, Starling RC, et al. Multicenter intravascular ultrasound validation study among heart transplant recipients: outcome after five years. J Am Coll Cardiol. 2005;45(9):1532–1537.
   PubMed Web of Science ®Google Scholar
• Wu GW, Kobashigawa JA, Fishbein MC, et al. Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 2009;28(5):417–422.
   PubMed Web of Science ®Google Scholar
• 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(9):847–858.
   PubMed Web of Science ®Google Scholar
• Eisen HJ, Kobashigawa J, Starling RC, et al. Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial. Am J Transplant. 2013;13(5):1203–1216.
   PubMed Web of Science ®Google Scholar
• Kobashigawa JA, Patel JK. Immunosuppression for heart transplantation: where are we now? Nat Clin Pract Cardiovasc Med. 2006;3(4):203–212.
   PubMedGoogle Scholar
• Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol. 2009;9:480–490.
   PubMed Web of Science ®Google Scholar
• Laurence A, Ghoreschi K, Hirahara K, et al. Therapeutic inhibition of the janus kinases. Inflamm Regen. 2012;32(1):16–22.
   Google Scholar
• Hsu L, Armstrong AW. JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014:283617.
   PubMed Web of Science ®Google Scholar
• Vincenti F, Tedesco Silva H, Busque S, et al. Randomized phase 2b trial of tofacitinib (CP-690,500) in de novo kidney transplant patients: efficacy, renal function and safety at 1 year. Am J Transplant. 2012;12:2446–2456.
   PubMed Web of Science ®Google Scholar
• Wu G, Chai N, Kim I, et al. Monoclonal anti-interleukin-6 receptor antibody attenuates donor-specific antibody responses in a mouse model of allosensitization. Transpl Immunol. 2013;28:138–143.
   PubMed Web of Science ®Google Scholar
• Vo AA, Choi J, Kim I, et al. A phase I/II trial of the interleukin-6 receptor-specific humanized monoclonal (Tocilizumab) + intravenous immunoglobulin in difficult to desensitize patients. Transplantation. 2015;99(11):2356–2363.
   PubMed Web of Science ®Google Scholar
• Person H, Soderberg JJ, Vindebro R, et al. Proteolytic processing of the streptococcal IgG endopeptidase IdeS modulates the functional properties of the enzyme and results in reduced immunorecognition. Mol Immunol. 2015;68(2A):176–184.
   PubMed Web of Science ®Google Scholar
• Jordan S, Choi J, Zhang X, et al. Initial Experience with the bacterial enzyme IdeS® (IgG endopeptidase) for desensitization of highly-HLA sensitized (HS) patients. [abstract]. Am J Transplant. 2016;16(suppl3):796-797.
   Google Scholar
• A phase II study to evaluate the efficacy of IdeS (IgG Endopeptidase) to desensitize transplant patients with a positive crossmatch test. [NCT02790437].
   Google Scholar
• Mohan R, Kobashigawa JA. Detecting rejection in cardiac transplantation: applications of genomic medicine. Per Med. 2016;13(3):257–264.
   PubMed Web of Science ®Google Scholar
• Pham MX, Teuteberg JJ, Kfoury AG, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010;362(20):1890–1900.
   PubMed Web of Science ®Google Scholar
• Kobashigawa J, Patel J, Azarbal B, et al. Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial. Circ Heart Fail. 2015;8(3):557–564.
   PubMed Web of Science ®Google Scholar
• Hollander Z, Chen V, Sidhu K, et al. Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression. J Heart Lung Transplant. 2013;32(2):259–265.
   PubMed Web of Science ®Google Scholar
• De Vlaminck I, Valantine HA, Snyder TM, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014;6(241):241ra277.
   Web of Science ®Google Scholar
• Grskovic M, Beausang J, Hiller D, et al. Plasma levels of donor-derived cell-free DNA increase with rejection and often decrease after treatment in organ transplant recipients. Presented at: American Transplant Congress; Philadelphia, PA; 2015. p. 83.
   Google Scholar
• Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012;13(5):358–369.
   PubMed Web of Science ®Google Scholar
• Duong Van Huyen JP, Tible M, Gay A, et al. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014;35(45):3194–3202.
   PubMed Web of Science ®Google Scholar
• Ravindra K, Leventhal J, Song D, et al. Chimerism and tolerance in solid organ transplantion. J Clin Cell Immunol. 2012;S9:001–003.
   Google Scholar
• Leventhal J, Abecassis M, Miller J, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med. 2012;4:124r28.
   Web of Science ®Google Scholar
• Leventhal J, Abecassis M, Miller J, et al. Tolerance induction in HLA disparate living donor kidney transplantation by donor stem call infusion: durable chimerism predicts outcome. Transplantation. 2013;95:169–176.
   PubMed Web of Science ®Google Scholar