Improved Survival with Perioperative Desensitization in Lung Transplant Patients with Donor Specific Antibodies (DSA)

Abstract

Purpose HLA antibodies and DSA are historically associated with decreased lung allograft survival and rejection, and are a barrier to lung transplant. Few results of interventions have been reported. We report the success of a perioperative desensitization protocol for sensitized lung recipients. Methods and Materials Recipients were tested for DSA at HLA A, B, C, DR and DQ. DSA+ patients were transplanted if PRA≥30% or high medical urgency and were desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin, and MMF instead of standard azathioprine(aza). Recipients with positive panel reactive antibodies (PRA+) but no DSA (DSA-) received MMF instead of aza. Routine therapy for unsensitized (PRA0) patients was cyclosporine, aza and prednisone without ATG. Results 340 first lung transplants were performed 2008-11: 53 DSA+, 93 PRA+DSA-,194 PRA0. Age, diagnosis, CMV status, single vs double lung, and donor characteristics (age, smoking, PaO 2 , donation after cardiac death, EVLP) were similar between groups. By Ab group (DSA+ / PRA+DSA- / PRA0): Median wait time to transplant was 167/92/100d (p=0.02). More DSA+ were female (62/44/36% p=0.003), and were urgent status at transplant (85/80/67% p=0.0005) with higher mean LAS (42/39/36 p=0.02). Despite increased pre-transplant morbidity, sensitized patients were less likely to experience any ≥ grade 2 acute rejection (9/9/18% p=0.04); max %predFEV1(81/74/76), %predFVC (81/77/79) and graft survival were equivalent between groups. [figure 1] Conclusions With this desensitization protocol, lung transplant can be safely performed in highly sensitized recipients with similar outcomes to unsensitized recipients.