Eculizumab as Salvage Therapy for Lung Transplant in a Sensitized Patient With a Positive T and B Cell Cross Match and Severe Allograft Dysfunction

Abstract

INTRODUCTION: HLA sensitization limits the pool of available donors for some patients needing lung transplantation. CASE PRESENTATION:A 53 year-old previously healthy female with UIP due to short telomere syndrome diagnosed by surgical lung biopsy presented to clinic with worsening hypoxemia and was admitted for a UIP flare. Over the next few days her hypoxemia progressed, with escalating supplemental oxygen re-quirements and inability to maintain adequate saturations. She underwent cannulation for veno-venous extra-corporeal membrane oxygenation (VV-ECMO) for support. Her transplant workup revealed multiple high titer (> 5000 MFI) Class I and II HLA antibodies with a calculated panel reactive antibody level of 76% (from 3% 1 month prior, likely due to ECMO and transfusion requirement). Most were complement fixing antibodies based on C1q fixation studies. After several incompatible donor offers, a donor with fewer cross reactive an-tigens became available, and a clinical decision was made to proceed with a bilateral lung trans-plantation despite a positive T and B cell donor-recipient flow cross match. The donor lungs were successfully implanted after standard induction with basiliximab and corticosteroids, followed by maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone. Eculizumab was added given complement fixation. The patient developed grade 3 primary graft dysfunction (PGD) needing continued VV-ECMO support. Infectious workup was negative, and transbronchial biopsy on postoperative day (POD) 3 demonstrated minimal acute rejection and severe acute lung injury, with no C4d staining. Thymoglobulin along with IVIG 2g/kg and Eculizumab 1200 mg iv was administered due to high clinical suspicion of concomitant antibody mediated rejection (AMR). Repeat biopsy POD 7 revealed improving rejection, positive C4d stain on capillary endothelium and positive donor specific antibody consistent with AMR. We continued Eculizumab biweekly at 1200 mg iv for 4 doses, and the patient progressively improved clinically and radiologically. VV-ECMO was discontinued on POD 8 and she was discharged home from the hospital on POD 26. She was seen in lung transplant clinic 3 months after transplant, on room air, and independent with activities of daily living.DISCUSSION: Eculizumab has been successfully utilized in renal transplantation to prevent, treat and salvage graft dysfunction due to AMR in sensitized patients. Similar use in managing HLA incompatibility and cross match positive transplants may help sensitized lung transplant candidates achieve their transplant with good outcomes. CONCLUSIONS:To our knowledge this is the first reported case of successful use of Eculizumab for salvage of severe lung allograft failure due to AMR in a sensitized patient with a known positive T and B cell cross match at the time of transplantation.