What is the standard immunosuppressive protocol—including induction agents, maintenance drugs and doses, therapeutic drug monitoring, and infection prophylaxis—for adult lung transplant recipients?

Immunosuppression Principles in Lung Transplantation

Standard Maintenance Immunosuppression Protocol

The standard maintenance immunosuppression for adult lung transplant recipients consists of triple-drug therapy: tacrolimus (preferred calcineurin inhibitor), mycophenolate mofetil (preferred antiproliferative), and corticosteroids. 1, 2, 3, 4, 5

Calcineurin Inhibitor Selection and Dosing

• Tacrolimus is the preferred calcineurin inhibitor over cyclosporine, with target therapeutic trough blood levels of 5-15 ng/mL once steady state is achieved 1
• For patients developing bronchiolitis obliterans syndrome (BOS) while on cyclosporine, switching to tacrolimus is recommended to mitigate lung function decline 1
• Therapeutic drug monitoring of tacrolimus trough levels is mandatory to avoid toxicities 6

Antiproliferative Agent Selection

• Mycophenolate mofetil (MPA) has largely replaced azathioprine as the preferred antiproliferative agent in modern protocols 2, 3, 4
• For patients developing adverse GI effects including diarrhea on mycophenolic acid, interruption of therapy or dose reduction is recommended 6
• If signs or symptoms of progressive multifocal leukoencephalopathy develop, cessation of mycophenolic acid is suggested 6

Corticosteroid Management

• Corticosteroids remain a core component of triple-drug maintenance therapy 2, 3, 4, 5
• Long-term high-dose corticosteroids (>30 mg/day of prednisone) should be avoided in lung transplant recipients who develop BOS 1

Induction Therapy

Approximately 50% of lung transplant centers utilize induction therapy, though its role remains controversial with no demonstrated survival benefit to date 2, 3, 4

Induction Agent Options

• Basiliximab (IL-2 receptor antagonist): Two doses of 20 mg each for adults ≥35 kg, or 10 mg each for patients <35 kg 7

  • First dose given within 2 hours prior to transplantation surgery 7
  • Second dose given 4 days after transplantation 7
  • Withhold second dose if severe hypersensitivity reactions or graft loss occur 7

• Polyclonal antibody preparations (equine or rabbit anti-thymocyte globulin) are alternative induction options 3

• Alemtuzumab is used at some centers, though less commonly 3

Evidence for Induction Therapy

• Addition of daclizumab (IL-2 receptor antagonist) to tacrolimus-based regimens decreased acute rejection episodes without increasing adverse events 8
• Induction therapy may reduce acute rejection but does not lower chronic rejection incidence or improve survival 2

Therapeutic Drug Monitoring Requirements

Regular monitoring of blood levels is essential for calcineurin inhibitors to avoid toxicities 1

Specific Monitoring Parameters

• Tacrolimus trough levels: Target 5-15 ng/mL 1
• CBC with differential for all patients receiving drugs associated with bone marrow suppression 1
• Sirolimus drug concentration monitoring if mTOR inhibitors are used 6
• Cholesterol and triglyceride levels prior to and during mTOR inhibitor therapy 6
• Creatinine and blood pressure monitoring for patients on mTOR inhibitors 6

Management of Acute Cellular Rejection

For non-minimal acute cellular rejection (Grade ≥A2) or lymphocytic bronchiolitis, augmented immunosuppression with systemic steroids is recommended to prevent BOS development 1

Rejection Treatment Protocol

• Intravenous methylprednisolone 1000 mg daily for 3 days (or 10-15 mg/kg/day in smaller patients) 1
• This augmented steroid therapy is indicated for non-minimal acute cellular rejection to prevent progression to chronic rejection 1

Special Considerations and Contraindications

mTOR Inhibitor Restrictions

• Sirolimus administration during the early perioperative period is contraindicated due to risk of airway dehiscence 6
• Avoid mTOR therapy or carefully monitor triglycerides in patients with abnormal elevation of fasting triglycerides 6
• Monitor for hyperlipidemia during mTOR therapy 6
• Evaluate for sirolimus-induced pulmonary toxicity if new or worsening respiratory symptoms develop 6

Infection Prophylaxis Considerations

• Infection is a major complication of immunosuppressive therapy, with combination therapy increasing risk for opportunistic infections 1
• Vaccination responses may be impaired in transplant recipients on immunosuppression 1

Adjunctive Therapy for Bronchiolitis Obliterans Syndrome

Azithromycin is recommended as trial therapy for lung transplant recipients who develop BOS: 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months 1

Clinical Pitfalls to Avoid

• Do not use conventional triple-drug therapy expecting protection from chronic lung allograft dysfunction—despite more potent regimens with tacrolimus and mycophenolate, these have not translated into significant protection from BOS development 2, 4
• Avoid re-exposure to basiliximab in patients previously administered this agent except with extreme caution due to potential hypersensitivity risk 7
• Do not administer other drug substances simultaneously through the same intravenous line as basiliximab 7