Induction immunosuppression following lung transplantation
- Sangeeta Bhorade, MD
Sangeeta Bhorade, MD
- Associate Professor of Medicine, Medical Director, Lung Transplant Program
- Northwestern University Feinberg School of Medicine
- Robert M Kotloff, MD
Robert M Kotloff, MD
- Chairman, Department of Pulmonary Medicine
- Respiratory Institute Cleveland Clinic
One of the major accomplishments of the first successful lung transplantation in 1963 was the prevention of allograft rejection by using azathioprine, prednisone, and Cobalt-60 irradiation to suppress the recipient immune system . Since then, great progress has been made in developing immunosuppression regimens to prevent acute and chronic rejection (bronchiolitis obliterans syndrome) of the lung allograft and to reduce the risk of opportunistic infection, a major side effect of immunosuppression.
The protocols for immunosuppressive therapy following lung transplantation can be divided into three general categories: induction, maintenance, and treatment of rejection. Strategies for induction of immunosuppression in the lung transplant recipient will be reviewed here. Maintenance immunosuppression, the immunology of solid organ transplantation, and the diagnosis and treatment of acute and chronic lung transplant rejection are discussed separately. (See "Maintenance immunosuppression following lung transplantation" and "Transplantation immunobiology" and "Evaluation and treatment of acute lung transplant rejection" and "Chronic lung transplant rejection: Bronchiolitis obliterans".)
Three general principles govern immunosuppressive therapy following lung transplantation.
●The first principle is that immune reactivity and the tendency toward graft rejection are highest in the first six months after graft implantation and decrease with time. Thus, most regimens employ the highest intensity of immunosuppression immediately after surgery and decrease the intensity of therapy over the first year, eventually settling on the lowest maintenance levels of immunosuppression that are compatible with preventing graft rejection.
●The second principle is that using low doses of several drugs with non-overlapping toxicities is preferable to higher (and more toxic) doses of fewer drugs whenever feasible. Combination regimens also help to block the many components of the complex immunological cascade that leads to allograft rejection.
- Blumenstock DA, Lewis C. The first transplantation of the lung in a human revisited. Ann Thorac Surg 1993; 56:1423.
- Yusen RD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015; 34:1264.
- Lake KD. Immunosuppressive drugs and novel strategies to prevent acute and chronic allograft rejection. Semin Respir Crit Care Med 2001; 22:559.
- International Society for Heart and Lung Transplantation Registry. Adult Lung Transplantation Statistics, 2014. https://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry (Accessed on November 07, 2014).
- Swarup R, Allenspach LL, Nemeh HW, et al. Timing of basiliximab induction and development of acute rejection in lung transplant patients. J Heart Lung Transplant 2011; 30:1228.
- Mullen JC, Oreopoulos A, Lien DC, et al. A randomized, controlled trial of daclizumab vs anti-thymocyte globulin induction for lung transplantation. J Heart Lung Transplant 2007; 26:504.
- Bamgbola FO, Del Rio M, Kaskel FJ, Flynn JT. Non-cardiogenic pulmonary edema during basiliximab induction in three adolescent renal transplant patients. Pediatr Transplant 2003; 7:315.
- Flynn JM, Byrd JC. Campath-1H monoclonal antibody therapy. Curr Opin Oncol 2000; 12:574.
- Calne R, Friend P, Moffatt S, et al. Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet 1998; 351:1701.
- Shyu S, Dew MA, Pilewski JM, et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant 2011; 30:743.
- Morris PJ, Russell NK. Alemtuzumab (Campath-1H): a systematic review in organ transplantation. Transplantation 2006; 81:1361.
- Peleg AY, Husain S, Kwak EJ, et al. Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody. Clin Infect Dis 2007; 44:204.
- Sachdeva A, Matuschak GM. Diffuse alveolar hemorrhage following alemtuzumab. Chest 2008; 133:1476.
- Snell GI, Westall GP, Levvey BJ, et al. A randomized, double-blind, placebo-controlled, multicenter study of rabbit ATG in the prophylaxis of acute rejection in lung transplantation. Am J Transplant 2014; 14:1191.
- Bhorade SM, Stern E. Immunosuppression for lung transplantation. Proc Am Thorac Soc 2009; 6:47.
- Costanzo-Nordin MR. Cardiopulmonary effects of OKT3: determinants of hypotension, pulmonary edema, and cardiac dysfunction. Transplant Proc 1993; 25:21.
- Figg WD. Aseptic meningitis associated with muromonab-CD3. DICP 1991; 25:1395.
- Wain JC, Wright CD, Ryan DP, et al. Induction immunosuppression for lung transplantation with OKT3. Ann Thorac Surg 1999; 67:187.
- Hachem RR, Edwards LB, Yusen RD, et al. The impact of induction on survival after lung transplantation: an analysis of the International Society for Heart and Lung Transplantation Registry. Clin Transplant 2008; 22:603.
- Hartwig MG, Snyder LD, Appel JZ 3rd, et al. Rabbit anti-thymocyte globulin induction therapy does not prolong survival after lung transplantation. J Heart Lung Transplant 2008; 27:547.
- Garrity ER Jr, Villanueva J, Bhorade SM, et al. Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody. Transplantation 2001; 71:773.
- Hachem RR, Chakinala MM, Yusen RD, et al. A comparison of basiliximab and anti-thymocyte globulin as induction agents after lung transplantation. J Heart Lung Transplant 2005; 24:1320.
- Burton CM, Andersen CB, Jensen AS, et al. The incidence of acute cellular rejection after lung transplantation: a comparative study of anti-thymocyte globulin and daclizumab. J Heart Lung Transplant 2006; 25:638.
- Floreth T, Bhorade SM, Ahya VN. Conventional and novel approaches to immunosuppression. Clin Chest Med 2011; 32:265.
- Wieland E, Olbricht CJ, Süsal C, et al. Biomarkers as a tool for management of immunosuppression in transplant patients. Ther Drug Monit 2010; 32:560.
- Penninga L, Møller CH, Penninga EI, et al. Antibody induction therapy for lung transplant recipients. Cochrane Database Syst Rev 2013; :CD008927.
- GENERAL PRINCIPLES
- INDUCTION THERAPY
- Indications and contraindications
- Induction agents
- - Basiliximab/daclizumab
- - Alemtuzumab
- - Anti-thymocyte globulin
- - Muromonab-CD3
- Efficacy of induction therapy
- - Effect on survival
- - Effect on rejection
- Choosing an agent
- PREVENTION OF OPPORTUNISTIC INFECTION
- FUTURE DIRECTIONS
- SUMMARY AND RECOMMENDATIONS