Extracorporeal photopheresis for the treatment of antibody mediated rejection following cardiac transplant

Antibody-mediated rejection (AMR) remains a major cause of graft dysfunction after heart transplantation. Extracorporeal photopheresis (ECP), primarily used for cellular rejection, has been evaluated as adjunct therapy for AMR in small case series. Given the rarity of cases, the effectiveness of ECP in recurrent, treatment-refractory AMR remains incompletely defined. We describe three long-term orthotopic heart transplant recipients with recurrent biopsy-proven AMR treated with ECP and summarize their histologic, serologic, and hemodynamic trajectories. This single-institution case series includes all identified patients with treatment-refractory AMR post-heart transplant treated with ECP over the past 10 years. All patients had recurrent pAMR1-2 with dominant class II donor-specific antibodies (DSA) despite intensive conventional therapy. We analyzed serial histology (ISHLT AMR grade; C4d), DSA trends, echocardiography, and invasive hemodynamics before, during, and after ECP. Patient 1 (47 ECP procedures, ~5.5 months) converted from pAMR2/pAMR1 to sustained pAMR0/C4d-, with improved filling pressures, preserved function, and long-term graft survival despite only partial DSA reduction. Patient 2 (31 ECP procedures, ~3.5 months) showed rapid histologic resolution and modest ejection fraction improvement but persistent hemodynamic impairment; she later developed chronic dysfunction and died from arrhythmia. Patient 3 (prolonged twice-weekly ECP) improved from pAMR2/C4d+ to durable pAMR0/C4d- with normalization of filling pressures and excellent graft function despite persistent high-titer DSA eight years post-ECP. Prospective studies are needed to define optimal patient selection and endpoints.