Immunosuppressive Therapy in Lung Transplantation

Author(s): Juan C. Fernandez-Castillo, Marcelo Cypel*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 28 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Long term survival and quality of life after lung transplantation are still affected by the development of chronic lung graft dysfunction (CLAD). CLAD is the number one cause of death one year after transplant; and there is no effective therapy available to date. Transplant centers’ approaches include perioperative immunosuppression, maintenance immunosuppression, and the treatment of eventual rejection. This review will focus on maintenance immunosuppression and the available data that support these strategies, as well as a brief description of our desensitization protocol and immunologic risk stratification. Optimization of immunosuppression is key to increase survival and graft function in transplant recipients, mostly through the combination of drugs. Since the therapeutic options to manage CLAD are still very limited, more studies are necessary to test new therapies and to clarify the potential role of new agents.

Keywords: Lung transplantation, chronic lung graft dysfunction, review, immunosuppression, risk stratification, transplant.

[1]
Szczech LA, Berlin JA, Aradhye S, Grossman RA, Feldman HI. Effect of anti-lymphocyte induction therapy on renal allograft survival: a meta-analysis. J Am Soc Nephrol 1997; 8(11): 1771-7.
[PMID: 9355081]
[2]
Szczech LA, Feldman HI. Effect of anti-lymphocyte antibody induction therapy on renal allograft survival. Transplant Proc 1999 May; 31(3B Suppl): 9S-11S.
[http://dx.doi.org/10.1016/S0041-1345(99)00094-9] [PMID: 10330960]
[3]
Mourad G, Garrigue V, Squifflet JP, et al. Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression. Transplantation 2001; 72(6): 1050-5.
[http://dx.doi.org/10.1097/00007890-200109270-00012] [PMID: 11579299]
[4]
Christie JD, Edwards LB, Kucheryavaya AY, et al. International Society of Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant 2012; 31(10): 1073-86.
[http://dx.doi.org/10.1016/j.healun.2012.08.004] [PMID: 22975097]
[5]
Yusen RD, Edwards LB, Dipchand AI, et al. The registry of the international society for heart and lung transplantation: thirty-third adult lung and heart-lung transplant report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant 2016; 35(10): 1170-84.
[PMID: 27772669]
[6]
Garrity ER Jr, Villanueva J, Bhorade SM, Husain AN, Vigneswaran WT. Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody. Transplantation 2001; 71(6): 773-7.
[http://dx.doi.org/10.1097/00007890-200103270-00015] [PMID: 11330541]
[7]
Borro JM, De la Torre M, Míguelez C, Fernandez R, Gonzalez D, Lemos C. Comparative study of basiliximab treatment in lung transplantation. Transplant Proc 2005; 37(9): 3996-8.
[http://dx.doi.org/10.1016/j.transproceed.2005.09.192] [PMID: 16386608]
[8]
Palmer SM, Miralles AP, Lawrence CM, Gaynor JW, Davis RD, Tapson VF. Rabbit antithymocyte globulin decreases acute rejection after lung transplantation: results of a randomized, prospective study. Chest 1999; 116(1): 127-33.
[http://dx.doi.org/10.1378/chest.116.1.127] [PMID: 10424515]
[9]
Hartwig MG, Snyder LD, Appel JZ III, et al. Rabbit anti-thymocyte globulin induction therapy does not prolong survival after lung transplantation. J Heart Lung Transplant 2008; 27(5): 547-53.
[http://dx.doi.org/10.1016/j.healun.2008.01.022] [PMID: 18442722]
[10]
Morris PJ, Russell NK. Alemtuzumab (Campath-1H): a systematic review in organ transplantation. Transplantation 2006; 81(10): 1361-7.
[http://dx.doi.org/10.1097/01.tp.0000219235.97036.9c] [PMID: 16732169]
[11]
Shyu S, Dew MA, Pilewski JM, et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant 2011; 30(7): 743-54.
[http://dx.doi.org/10.1016/j.healun.2011.01.714] [PMID: 21420318]
[12]
Furuya Y, Jayarajan SN, Taghavi S, et al. the impact of alemtuzumab and basiliximab induction on patient survival and time to bronchiolitis obliterans syndrome in double lung transplantation recipients. Am J Transplant 2016 Aug; 16(8): 2334-41.
[http://dx.doi.org/10.1111/ajt.13739] [PMID: 26833657]
[13]
Calne RY, White DJ, Evans DB, et al. Cyclosporin A in cadaveric organ transplantation. Br Med J (Clin Res Ed) 1981; 282(6268): 934-6.
[http://dx.doi.org/10.1136/bmj.282.6268.934] [PMID: 6781658]
[14]
Griffith BP, Bando K, Hardesty RL, et al. A prospective randomized trial of FK506 versus cyclosporine after human pulmonary transplantation. Transplantation 1994; 57(6): 848-51.
[http://dx.doi.org/10.1097/00007890-199403270-00013] [PMID: 7512292]
[15]
Keenan RJ, Konishi H, Kawai A, et al. Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg 1995; 60(3): 580-4.
[http://dx.doi.org/10.1016/0003-4975(95)00407-C] [PMID: 7545889]
[16]
Zuckermann A, Reichenspurner H, Birsan T, et al. Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomized trial. J Thorac Cardiovasc Surg 2003; 125(4): 891-900.
[http://dx.doi.org/10.1067/mtc.2003.71] [PMID: 12698153]
[17]
Treede H, Klepetko W, Reichenspurner H, et al. Munich and Vienna Lung Transplant Group. Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols. J Heart Lung Transplant 2001; 20(5): 511-7.
[http://dx.doi.org/10.1016/S1053-2498(01)00244-3] [PMID: 11343977]
[18]
Treede H, Glanville AR, Klepetko W, et al. European and Australian Investigators in Lung Transplantation. Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation. J Heart Lung Transplant 2012; 31(8): 797-804.
[http://dx.doi.org/10.1016/j.healun.2012.03.008] [PMID: 22554673]
[19]
Palmer SM, Baz MA, Sanders L, et al. Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection. Transplantation 2001; 71(12): 1772-6.
[http://dx.doi.org/10.1097/00007890-200106270-00012] [PMID: 11455257]
[20]
McNeil K, Glanville AR, Wahlers T, et al. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation 2006; 81(7): 998-1003.
[http://dx.doi.org/10.1097/01.tp.0000202755.33883.61] [PMID: 16612275]
[21]
Taylor AL, Watson CJ, Bradley JA. Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol 2005; 56(1): 23-46.
[http://dx.doi.org/10.1016/j.critrevonc.2005.03.012] [PMID: 16039869]
[22]
Arora S, Gude E, Sigurdardottir V, et al. Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: the significance of baseline glomerular filtration rate. J Heart Lung Transplant 2012; 31(3): 259-65.
[http://dx.doi.org/10.1016/j.healun.2011.12.010] [PMID: 22333403]
[23]
Gullestad L, Iversen M, Mortensen SA, et al. Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial. Transplantation 2010; 89(7): 864-72.
[http://dx.doi.org/10.1097/TP.0b013e3181cbac2d] [PMID: 20061999]
[24]
Gullestad L, Mortensen SA, Eiskjær H, et al. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial. Transplantation 2010; 90(12): 1581-9.
[http://dx.doi.org/10.1097/TP.0b013e3181fd01b7] [PMID: 21030905]
[25]
Snell GI, Valentine VG, Vitulo P, et al. RAD B159 Study Group. Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Am J Transplant 2006; 6(1): 169-77.
[http://dx.doi.org/10.1111/j.1600-6143.2005.01134.x] [PMID: 16433771]
[26]
Bhorade S, Ahya VN, Baz MA, et al. Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. Am J Respir Crit Care Med 2011; 183(3): 379-87.
[http://dx.doi.org/10.1164/rccm.201005-0775OC] [PMID: 20833822]
[27]
Strueber M, Warnecke G, Fuge J, et al. Everolimus versus mycophenolate mofetil de novo after lung transplantation: a prospective, randomized, open-label trial. Am J Transplant 2016; 1116(11): 3171-80.
[PMID: 27104933.]
[28]
Glanville AR, Aboyoun C, Klepetko W, et al. European and Australian Investigators in Lung Transplantation. Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation. J Heart Lung Transplant 2015; 34(1): 16-25.
[http://dx.doi.org/10.1016/j.healun.2014.06.001] [PMID: 25049068]
[29]
Larsen CP, Grinyó J, Medina-Pestana J, et al. Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies. Transplantation 2010; 90(12): 1528-35.
[http://dx.doi.org/10.1097/TP.0b013e3181ff87cd] [PMID: 21076381]
[30]
Martin ST, Tichy EM, Gabardi S. Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation. Pharmacotherapy 2011; 31(4): 394-407.
[http://dx.doi.org/10.1592/phco.31.4.394] [PMID: 21449628]
[31]
Iasella CJ, Winstead RJ, Moore CA, et al. Maintenance belatacept based immunosuppression in lung transplantation recipients who failed calcineurin inhibitors. Transplantation 2018; 01102(1): 171-7. eng
[http://dx.doi.org/10.1097/TP.0000000000001873] [PMID: 28691954]
[32]
Yamada Y, Langner T, Inci I, et al. Impact of human leukocyte antigen mismatch on lung transplant outcome. Interact Cardiovasc Thorac Surg 2018; 0526(5): 859-64.
[http://dx.doi.org/10.1093/icvts/ivx412] [PMID: 29300898.]
[33]
Brugière O, Suberbielle C, Thabut G, et al. Lung transplantation in patients with pretransplantation donor-specific antibodies detected by Luminex assay. Transplantation 2013; 95(5): 761-5.
[http://dx.doi.org/10.1097/TP.0b013e31827afb0f] [PMID: 23296148]
[34]
Palmer SM, Davis RD, Hadjiliadis D, et al. Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Transplantation 2002; 74(6): 799-804.
[http://dx.doi.org/10.1097/00007890-200209270-00011] [PMID: 12364858]
[35]
Snyder LD, Gray AL, Reynolds JM, et al. Antibody desensitization therapy in highly sensitized lung transplant candidates. Am J Transplant 2014; 14(4): 849-56.
[http://dx.doi.org/10.1111/ajt.12636] [PMID: 24666831]
[36]
Tinckam KJ, Keshavjee S, Chaparro C, et al. Survival in sensitized lung transplant recipients with perioperative desensitization. Am J Transplant 2015; 15(2): 417-26.
[http://dx.doi.org/10.1111/ajt.13076] [PMID: 25612494]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 28
Year: 2020
Published on: 30 August, 2020
Page: [3385 - 3388]
Pages: 4
DOI: 10.2174/1381612826666200628023150
Price: $65

Article Metrics

PDF: 33
HTML: 5