Treatment of Antibody-Mediated Rejection (AMR) Post Lung Transplantation
Primary therapy for AMR post lung transplantation should include a combination of plasmapheresis, intravenous immunoglobulin (IVIg), high-dose corticosteroids, and rituximab. 1, 2
First-Line Treatment Protocol
- High-dose corticosteroids (methylprednisolone 500-1000 mg IV daily for 3 days) should be initiated immediately upon suspicion of AMR 3
- Plasmapheresis should be performed daily or every other day for a minimum of 5 sessions to remove circulating donor-specific antibodies (DSAs) 3, 4
- IVIg (2 g/kg divided into doses) should be administered after plasmapheresis sessions 3, 2
- Rituximab (375 mg/m² weekly for up to 4 doses) should be added to target B cells 3, 5
Second-Line Therapy for Refractory Cases
- Bortezomib (1.3 mg/m² on days 1,4,7, and 10) should be added for cases not responding to first-line therapy 3, 6
- Anti-complement antibodies may be considered for severe or persistent cases 3
- Total lymphoid irradiation or photopheresis may be considered for refractory cases 3
Optimization of Maintenance Immunosuppression
- Consider switching from cyclosporine-based immunosuppression to tacrolimus 3
- Consider increasing the dose of mycophenolate mofetil (MMF) or substituting with sirolimus 3
- Cyclophosphamide (0.5-1 g/m² every 3 weeks for 4-6 months) may be considered as an alternative to MMF 3
Treatment Monitoring and Duration
- Monitor DSA levels before and after treatment to assess response 4, 2
- Continue treatment until clinical improvement and reduction or elimination of DSAs 1, 4
- Perform follow-up biopsies to assess histological improvement 3
Special Considerations
- Patients with hemodynamic compromise may require additional support with inotropes, but use caution with vasopressors in patients with hypertrophic obstructive cardiomyopathy 7
- Dilution testing of DSAs may help predict response to standard treatment protocols; patients with high MFI values in 1:16 diluted sera may require more aggressive treatment 4
- Be aware that treatment complications include thrombocytopenia (50% of patients) and gastrointestinal discomfort (18.7% of patients) 6
Treatment Outcomes
- Approximately 27-36% of patients may clear DSAs and preserve allograft function at 6 months post-treatment 6
- Patients who develop AMR after already having chronic lung allograft dysfunction have poorer outcomes 5
- Early identification and treatment of AMR before the development of chronic lung allograft dysfunction may lead to better long-term outcomes 5
Risk Stratification
- Patients with positive DSA and allograft dysfunction have the highest risk and should receive full treatment protocol 1, 2
- Patients with positive DSA but without clinical symptoms may be monitored without aggressive treatment in some cases 1
- The severity of AMR (based on histopathology, C4d staining, and DSA levels) should guide the intensity of treatment 3, 1