ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Induction immunosuppression following lung transplantation

Induction immunosuppression following lung transplantation
Literature review current through: Jan 2024.
This topic last updated: Nov 02, 2022.

INTRODUCTION — One of the major accomplishments of the first lung transplantation in 1963 was the prevention of allograft rejection by using azathioprine, prednisone, and Cobalt-60 irradiation to suppress the recipient immune system [1]. Since then, great progress has been made in developing immunosuppression regimens to prevent acute and chronic rejection of the lung allograft while also aiming 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".)

(See "Transplantation immunobiology".)

(See "Evaluation and treatment of acute cellular lung transplant rejection".)

(See "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome".)

GENERAL PRINCIPLES — Three general principles govern immunosuppressive therapy following lung transplantation.

Deceleration – 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.

Combination – 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.

Moderation – The third principle is to avoid over-immunosuppression, because it leads to undesirable adverse effects, such as susceptibility to infection and malignancy. (See "Infection in the solid organ transplant recipient" and "Malignancy after solid organ transplantation" and "Treatment and prevention of post-transplant lymphoproliferative disorders".)

The immunosuppressive strategies used in lung transplantation have capitalized on the experiences with transplantation of other solid organs. However, there is no consensus regarding the optimal regimen for immunosuppression following lung transplantation [2]. In addition, none of the immunosuppressive medications is approved by the US Food and Drug Administration for use in lung transplantation.

INDUCTION THERAPY — Induction therapy is the brief utilization of a potent immunosuppressive agent in the immediate post-transplant period to reduce the initial robust immune response of T cells to the transplanted organ. Induction agents focus on depletion of T cells and/or interruption of T cell activation and proliferation, as T cells are felt to be the primary mediators of rejection. T cell recognition of antigens on the transplanted lung initiates calcineurin-mediated stimulation of the transcription, translation, and secretion of interleukin-2 (IL-2), an essential growth factor for T-cell proliferation. Interruption of IL-2 activity suppresses T cell proliferation. (See "Transplantation immunobiology".)

Induction agents can be classified into two groups: monoclonal agents (eg, IL-2 antagonists [basiliximab], alemtuzumab [limited availability], muromonab-CD3 [no longer available]), and polyclonal agents (eg, anti-lymphocyte and anti-thymocyte globulins) (table 1).

The administration of high-dose glucocorticoids (eg, methylprednisolone 500 to 1000 mg intravenous) intraoperatively just before perfusion of the lung allograft is designed to reduce the risk of reperfusion injury. It is generally not considered part of induction therapy, although it probably contributes to the initial immunosuppression. (See "Lung transplantation: Procedure and postoperative management", section on 'Initiation of immunosuppression'.)

Indications and contraindications — The use of induction therapy remains controversial in lung transplantation although an increasing number of transplant programs, including ours, are using some form of it. According to the International Society for Heart and Lung Transplantation (ISHLT) registry, the use of induction therapy for lung transplantation increased from 43 percent in 2005 to 81 percent in 2018 [2].

In some centers, use of induction therapy may be tailored to the individual patient. For example, in older lung transplant recipients (>65 years) or in patients who are at higher risk of infection (eg, CMV serologic status of +donor/-recipient; cystic fibrosis with highly resistant organisms), induction therapy is often withheld. In others, such as highly sensitized patients (ie, those who have pre-formed panel reactive antibodies [PRA] to the donor MHC antigens), induction therapy is given. (See "Evaluation and treatment of antibody-mediated lung transplant rejection", section on 'Laboratory'.)

Induction agents — Information regarding mechanism of action, dosing, monitoring, and side effects are summarized in the table (table 1).

Interleukin-2 receptor antagonist — Basiliximab is a chimeric murine/human monoclonal antibody preparation that is specific for and binds with high affinity to the alpha subunit of the interleukin-2 receptor (IL-2R, CD25) on activated T cells. Thus, basiliximab inhibits IL-2 mediated proliferation and differentiation of T cells, but does not deplete them. Daclizumab, another IL-2R antagonist, is no longer commercially available.

According to the ISHLT registry, induction therapy with an IL-2R-antagonist was used in 71 percent of lung transplants performed from January to June 2018 [2].

Basiliximab is administered intraoperatively or immediately following lung transplant and again on the fourth post-transplant day (table 1) [3,4]. The dose for adults and children weighing over 35 kg is 20 mg, infused intravenously over 20 to 30 minutes.

Being humanized, basiliximab is generally well-tolerated and does not cause the cytokine release syndrome typical of muromonab-CD3 and alemtuzumab. There are rare reports of severe, noncardiogenic pulmonary edema temporally related to the use of basiliximab induction therapy in renal transplant recipients [5].

Anti-thymocyte globulin — The anti-lymphocyte/anti-thymocyte globulins are polyclonal immunoglobulin preparations created from horses (horse antithymocyte globulin, equine ATG, eATG, Atgam) or rabbits (rabbit antithymocyte globulin, rabbit ATG, rATG, Thymoglobulin) with antibodies against human T cells. Antithymocyte globulins act through the Fc receptor and other proteins on the surface of T cells to deplete cytotoxic T cells. With the introduction of IL-2R antagonists, few centers continue to utilize anti-thymocyte globulin preparations for induction [6].

Dose and administration – The typical regimen for rabbit antithymocyte globulin (Thymoglobulin) is 1.5 mg/kg administered intravenously on day one and then two or three additional doses given 24 hours apart (table 1). The initial dose is infused over at least six hours through a high-flow vein; subsequent doses are administered over at least four hours. In general, lymphocyte subsets (CD3 >5 percent) are followed to determine whether to administer the subsequent daily doses. The typical regimen for administering horse antithymocyte globulin (Atgam) is intravenous administration of 5 to 15 mg/kg per day for the first 1 to 14 days following lung transplantation.

Adverse effects – Many patients have an acute reaction of fever, rigors, myalgias, rash, and tachycardia to initial administration. Premedication with glucocorticoids (eg, methylprednisolone 125 mg intravenously), antihistamines (eg, diphenhydramine 50 mg orally or intravenously), and antipyretics (eg, acetaminophen 1 g orally) one hour prior to infusion can prevent or reduce infusion-related symptoms.

In addition to infusion-related symptoms, antithymocyte globulin therapy is associated with leukopenia, thrombocytopenia, immune-complex-mediated glomerulonephritis, and rarely, serum sickness [7].

Agents with limited or no availability

Alemtuzumab — Alemtuzumab (Campath-1H) is a humanized preparation of monoclonal rat antibodies directed toward the CD52 antigen that is present on virtually all lymphocytes (both T and B cells). Alemtuzumab leads to depletion of T cells through complement-mediated and direct cellular cytotoxicity [8]. Alemtuzumab has been used in the treatment of rheumatoid arthritis, lymphoid malignancies, graft-versus-host disease, and hematopoietic stem cell transplantation. It was first used as an induction agent in solid organ transplantation in 1998 and was used as an induction agent in approximately 5 percent of lung transplantations performed in 2018 [2,9]. Alemtuzumab is no longer commercially available in the United States and Europe; a restricted distribution program has been established by the manufacturer to allow access for appropriate patients.

The usual dose of alemtuzumab for induction of immunosuppression is 30 mg infused over two hours [10]. Like OKT3, alemtuzumab can cause a cytokine release syndrome with the first dose, characterized by fever and in more severe cases, by hypotension, hypoxemia, and end-organ dysfunction. This reaction is more modest than that seen with OKT3 and can be effectively prevented or attenuated by pre-emptive administration of methylprednisolone 15 mg/kg intravenously, diphenhydramine 50 mg orally or intravenously, and acetaminophen 500 to 1000 mg orally 30 minutes prior to initiation of alemtuzumab infusion. The prevention and management of acute infusion reactions to alemtuzumab are discussed separately. (See "Infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy", section on 'Alemtuzumab'.)

The lymphopenia that results from alemtuzumab is profound and long lasting; T cell levels (both CD4 and CD8) may remain significantly depressed for as long as three years [11]. Because the target CD52 antigen is also present on B cells, alemtuzumab leads to B cell lymphopenia as well, although of a shorter time period, typically about three months. In light of the profound and persistent immunosuppressive effects of alemtuzumab, use of this agent is typically followed by a reduced intensity maintenance immunosuppression regimen [10].

Use of alemtuzumab for induction or treatment of acute rejection has been noted to be an independent risk factor for opportunistic infection in a large study of 547 organ transplant recipients [12]. Diffuse alveolar hemorrhage, immune-mediated cytopenias, hemophagocytic lymphohistiocytosis, and autoimmune encephalitis have also been reported with the use of alemtuzumab [13,14].

Daclizumab — Daclizumab is a chimeric murine/human monoclonal antibody that is specific for and binds with high affinity to the alpha subunit of the interleukin-2 receptor (IL-2R, CD25) on activated T cells. It is no longer available.

Muromonab-CD3 — Muromonab-CD3 (OKT3) is a mouse monoclonal antibody that has been used as an induction agent to prevent acute lung transplant rejection since the 1980s. However, it is currently not used as induction therapy in lung transplantation due to the severe toxicities associated with this drug and is not available in the United States or Europe.

OKT3 binds to the T cell receptor-CD3 complex. This binding causes a reversible antigenic modification of the CD3 complex, leading to depletion of T cells, except for relative sparing of T regulatory cells [7]. (See "The adaptive cellular immune response: T cells and cytokines", section on 'T cell receptor-CD3 complex'.)

However, this significant depletion of T cells paradoxically activates a large number of new T cells, which then release massive amounts of cytokines. This activation results in a massive first-dose cytokine-release syndrome consisting of fever, rigors, nausea, vomiting, diarrhea, and in some severe cases, hemodynamic instability.

Other side effects associated with OKT3 include pulmonary edema in patients who are fluid overloaded at the time of administration and aseptic meningitis, which has been seen in 3 to 5 percent of patients receiving OKT3 [15,16]. Other side effects include mild elevations in pulmonary artery systolic pressure, mild reduction in oxygenation, and pyrexia that are self-limited, easily treated, and resolve within 12 hours [17].

Efficacy of induction therapy

Effect on survival — Randomized trials investigating the efficacy of induction therapy are limited [6,18,19]. A systematic review of six single center randomized trials evaluating the use of T-cell antibody induction with anti-thymocyte globulin, anti-lymphocyte globulin, IL-2 receptor antagonists, or alemtuzumab concluded that there were no clear benefits with respect to survival associated with use of induction regimens versus no induction [19]. However, the authors caution that the number of patients was relatively small and all identified studies were at high risk for methodological bias. A subsequent, multicenter trial, enrolling 223 patients randomized to induction with rabbit anti-lymphocyte globulin or no induction, failed to show a difference in survival at one year [6].

Most of the evidence suggesting efficacy of induction immunosuppression comes from analyses of large national/international patient registries and includes patients treated with agents that are no longer available (daclizumab and alemtuzumab).

According to data from the ISHLT registry, the use of any induction therapy compared with no induction therapy is associated with a slight but statistically significant improvement in survival contingent upon survival to 14 days post transplantation (p<0.0001) [2]. The difference between the groups was not apparent until at least a year following transplant. Notably, this analysis was not adjusted for potential confounders that might account for the observed difference.

In a more rigorous, but still retrospective, analysis of the ISHLT data on 3970 adult lung recipients transplanted between 2000 to 2004, survival at four years was better among those who received an IL-2 receptor antagonist (64 percent) or antithymocyte globulin (60 percent) compared with those who did not receive induction (57 percent) [20]. Use of induction was an independent predictor of survival in multivariable Cox analysis.

An analysis of 6117 patients in the UNOS database who received bilateral lung transplants between 2006 and 2013 documented superior survival among those receiving either basiliximab or alemtuzumab compared with no induction [21]. Similar to the previous study, the use of either induction agent was independently associated with improved survival on multivariable analysis. Notably, the prevalence of post-transplant lymphoproliferative disorder was increased in association with alemtuzumab (4.5 percent) compared with basiliximab (0.4 percent) or no induction (1.5 percent; p<0.001).

In a registry database study of 9019 lung transplant recipients, the combination of no induction agent plus sirolimus and tacrolimus was associated with longer survival compared with mycophenolate mofetil plus tacrolimus and an induction agent (basiliximab, daclizumab, antithymocyte globulin, alemtuzumab; adjusted hazard ratio 0.48; 95% CI 0.31-0.76) [22].

An analysis of 22,025 patients in the UNOS database who received lung transplants between 2006 and 2018 demonstrated lower long-term mortality among those receiving induction therapy with basiliximab (50 percent of the patients), alemtuzumab (7 percent of the patients), or antithymocyte globulin (6 percent of the patients) compared with those who did not receive induction therapy (36 percent of the patients) [23]. Further analysis of the basiliximab and "no-induction" groups utilizing propensity-score matching demonstrated a 14 percent lower risk of death among those receiving basiliximab and a 38 percent higher risk of an acute rejection episode in the group that did not receive induction therapy.

Finally, retrospective studies from two major transplant centers provide additional support for use of induction therapy:

A retrospective analysis of 336 lung transplant recipients at University of Pittsburgh who received induction with alemtuzumab, thymoglobulin, or daclizumab, or no induction therapy demonstrated superior survival at five years in the alemtuzumab (59 percent) and thymoglobulin (60 percent) groups compared with daclizumab (44 percent) or no induction (47 percent) groups [10]. (See 'Alemtuzumab' above and 'Anti-thymocyte globulin' above and 'Interleukin-2 receptor antagonist' above.)

A similarly conducted retrospective analysis of 231 lung transplant recipients from the University of Vienna revealed superior one- and five-year survival among those receiving alemtuzumab or antithymocyte globulin compared with no induction [24].

Effect on rejection — A number of studies, as well as the current ISHLT registry data, suggest that induction therapy is associated with a lower incidence of acute rejection [18,20,24-27] and greater freedom from bronchiolitis obliterans syndrome (BOS) [2,21,24,28]. However, these findings are not universal [6,18-20] and suffer from the same methodological limitations as the survival data. No single agent has consistently emerged as superior to others with respect to its impact on acute and chronic rejection.

Choosing an agent — The considerable methodological constraints and inconsistencies of available data preclude definitive endorsement of induction therapy or of a particular agent. In current practice, IL-2R antagonists are employed in approximately 70 percent of lung transplantations performed world-wide, while alemtuzumab and anti-lymphocyte/anti-thymocyte globulin are used in 5 and 4 percent of recipients, respectively [2]. The strong preference for IL-2R antagonists among centers employing induction protocols reflects their more favorable safety profile rather than demonstrated superior efficacy. (See 'Efficacy of induction therapy' above.)

PREVENTION OF OPPORTUNISTIC INFECTION — Opportunistic infection is a major side effect of immunosuppression for organ transplantation. Regimens for prophylaxis for bacterial, fungal, and viral infections after lung transplant are discussed separately. (See "Bacterial infections following lung transplantation", section on 'Prophylaxis' and "Bacterial infections following lung transplantation", section on 'Vaccination' and "Fungal infections following lung transplantation", section on 'Prophylaxis' and "Viral infections following lung transplantation", section on 'Summary and recommendations' and "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients".)

FUTURE DIRECTIONS — Future directions of induction therapy include a better understanding of the risks and benefits of induction therapy for each individual lung transplant recipient. In this era of personalized medicine, choosing and tailoring an appropriate induction agent for a given individual may ultimately improve outcomes. This individualized approach would require better prediction of a patient’s risk for infection and rejection as well as a better understanding of the net effect of immunosuppression for a given individual. In addition, performance of large prospective trials will be essential in defining the overall benefit of induction therapy in this population. One example of a prospective trial for an intriguing potential induction agent is the ongoing, single center trial of induction with extracorporeal photopheresis in patients with cystic fibrosis undergoing lung transplantation (NCT03500575) [29]. Additionally, there is an ongoing multicenter randomized trial evaluating tocilizumab versus placebo in heart transplantation that has the potential to influence lung transplantation practices (NCT03644667) [30].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lung transplantation".)

SUMMARY AND RECOMMENDATIONS

Definition – Induction therapy refers to the brief utilization of a potent immunosuppressive agent intraoperatively or in the immediate post-transplant period to reduce the initial robust immune response to the transplanted organ. (See 'Induction therapy' above.)

Rationale – The rationale behind induction immunosuppression is two-fold. First, induction regimens are designed to promote early and potent immunosuppression, as the tendency toward graft rejection is highest early (within the first three to six months) after graft implantation. Second, potent induction may enable a less toxic maintenance regimen to be successful. (See 'General principles' above.)

Approach – For most patients undergoing lung transplantation, we suggest use of an induction agent at the time of surgery (Grade 2C). However, it is also reasonable not to use induction therapy depending on the transplant center experience and recipient characteristics (eg, risk of post-transplant infection). All lung transplant recipients will need maintenance immunosuppression. (See 'Induction therapy' above and "Maintenance immunosuppression following lung transplantation".)

Induction agents – The induction agents used for lung transplantation are basiliximab, an interleukin-2 receptor (IL-2R) antagonist and antithymocyte globulin. Information about the administration of these agents and their potential adverse effects is provided in the table (table 1). (See 'Induction agents' above.)

High-dose glucocorticoids (eg, methylprednisolone 500 to 1000 mg intravenous) are typically administered intraoperatively just before perfusion of the lung allograft to reduce the risk of reperfusion injury. Glucocorticoid administration is generally not considered part of induction therapy, although it probably contributes to the initial immunosuppression. (See 'Induction therapy' above and "Lung transplantation: Procedure and postoperative management".)

Efficacy and choice of agent – Data on efficacy of the individual induction agents are insufficient to permit recommendation of a particular induction agent. Large cohort studies suggest a possible reduction in mortality and acute lung rejection in patients who receive induction therapy. Because the IL-2 receptor antagonists have a more favorable safety profile, they have emerged as the most commonly employed agents. (See 'Interleukin-2 receptor antagonist' above and 'Efficacy of induction therapy' above.)

Risks and benefits

Opportunistic infection is a major side effect of immunosuppression, including induction immunosuppression, for organ transplantation. Regimens for prophylaxis against bacterial, fungal and viral infections post-transplant are discussed separately. (See "Bacterial infections following lung transplantation", section on 'Prophylaxis' and "Bacterial infections following lung transplantation", section on 'Vaccination' and "Fungal infections following lung transplantation", section on 'Prophylaxis' and "Viral infections following lung transplantation", section on 'Summary and recommendations' and "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients".)

The goal of induction therapy is to reduce acute rejection. The diagnosis and treatment of acute and chronic lung transplant rejection are discussed in detail separately. (See "Evaluation and treatment of acute cellular lung transplant rejection" and "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Pamela McShane, MD, and Sangeeta Bhorade, MD, who contributed to earlier versions of this topic review.

  1. Blumenstock DA, Lewis C. The first transplantation of the lung in a human revisited. Ann Thorac Surg 1993; 56:1423.
  2. International Society for Heart and Lung Transplantation Registry. Adult Lung Transplantation Statistics. http://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry (Accessed on February 11, 2020).
  3. 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.
  4. Chung PA, Dilling DF. Immunosuppressive strategies in lung transplantation. Ann Transl Med 2020; 8:409.
  5. 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.
  6. 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.
  7. Bhorade SM, Stern E. Immunosuppression for lung transplantation. Proc Am Thorac Soc 2009; 6:47.
  8. Flynn JM, Byrd JC. Campath-1H monoclonal antibody therapy. Curr Opin Oncol 2000; 12:574.
  9. 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.
  10. Shyu S, Dew MA, Pilewski JM, et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant 2011; 30:743.
  11. Morris PJ, Russell NK. Alemtuzumab (Campath-1H): a systematic review in organ transplantation. Transplantation 2006; 81:1361.
  12. 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.
  13. Sachdeva A, Matuschak GM. Diffuse alveolar hemorrhage following alemtuzumab. Chest 2008; 133:1476.
  14. LEMTRADA (alemtuzumab) injection, for intravenous use. US Food and Drug Administration. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2022/103948s5185lbl.pdf (Accessed on June 10, 2022).
  15. Costanzo-Nordin MR. Cardiopulmonary effects of OKT3: determinants of hypotension, pulmonary edema, and cardiac dysfunction. Transplant Proc 1993; 25:21.
  16. Figg WD. Aseptic meningitis associated with muromonab-CD3. DICP 1991; 25:1395.
  17. Wain JC, Wright CD, Ryan DP, et al. Induction immunosuppression for lung transplantation with OKT3. Ann Thorac Surg 1999; 67:187.
  18. 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.
  19. Penninga L, Møller CH, Penninga EI, et al. Antibody induction therapy for lung transplant recipients. Cochrane Database Syst Rev 2013; :CD008927.
  20. 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.
  21. 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; 16:2334.
  22. Wijesinha M, Hirshon JM, Terrin M, et al. Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant. JAMA Netw Open 2019; 2:e1910297.
  23. Shagabayeva L, Osho AA, Moonsamy P, et al. Induction therapy in lung transplantation: A contemporary analysis of trends and outcomes. Clin Transplant 2022; 36:e14782.
  24. Benazzo A, Schwarz S, Muckenhuber M, et al. Alemtuzumab induction combined with reduced maintenance immunosuppression is associated with improved outcomes after lung transplantation: A single centre experience. PLoS One 2019; 14:e0210443.
  25. 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.
  26. 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.
  27. Jaksch P, Ankersmit J, Scheed A, et al. Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study. Am J Transplant 2014; 14:1839.
  28. 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.
  29. Righi I, Clerici M, Trabattoni D, et al.. Extracorporeal Photopheresis as Induction Therapy after Lung Transplantation for Cystic Fibrosis: Interim Analysis. J Heart Lung Transplant 2020; 39:S107.
  30. ClinicalTrials.gov. Tocilizumab in cardiac transplantation. https://clinicaltrials.gov/ct2/show/NCT03644667 (Accessed on October 18, 2022).
Topic 4661 Version 27.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟