Abstract 1822: Heart Transplantation in Pediatric HLA-Sensitized Patients
Background: There is an elevated risk for deleterious outcomes following heart transplant (HTx) in patients (pts) sensitized to human leukocyte antigens (HLA) including cellular (ACR) and antibody-mediated (AMR) rejection, and chronic rejection (CAD). Sensitized pts may be restricted to certain donors or excluded from HTx. Aggressive strategies are utilized to remove antibody and suppress B-cell function. We report our increasing positive experience with HLA-sensitized pediatric HTx recipients.
Methods: Retrospective review of HTx pt records with elevated pre-HTx Panel Reactive Antibody (PRA), [Class I /Class II] (>10%), and /or positive Tor B- cell crossmatch (XM).
Results: Fifteen pts were sensitized pre-HTx (6 female, 43%); median age at HTx 7 mos (3.5 mos-17.7 yrs). Ten were infants (<12 mos); 9 had prior surgical palliation, 1 cardiomyopathy (CM). There were 5 older pts (median 12 yrs; 4.8–17.7 yrs): 1 CM, 2 congenital heart disease, 2 re-Tx. Management: Intra-operative plasma exchange. Induction therapy with thymoglobulin. Day 1 post-HTx XM; if +XM, plasmapheresis. B-cell therapies (cyclophosphamide or rituximab) in 13/15 pts, guided by FACS assessment of CD20+ cells. Immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Daily pheresis ± cytogam/IVIG if +XM, with a gradual, biopsy-guided (immunoflourescence for Ig and C4d) weaning schedule.
Early experience: rituximab when AMR detected on biopsy. Recently (n=3), rituximab used empirically pre-HTx. Histological evidence of early AMR confirmed in 9/15 pts within median 1 mo post-HTx (1 wk-1.5 mos); 7/15 had early moderate ACR (>3A or 2 R). There were 3 deaths: 11 days (severe ACR and AMR), 3 mos (aspiration), and 9 mos (infection, MSOF; unsuspected severe CAD on autopsy despite normal echo). Median follow-up of 12 survivors was 1.02 yrs (1 wk-3.63 yrs). Of 8 pts > 6 mos post-HTx, pheresis required from 2–5 mos post-HTx, none had significant AMR since mean 1.9+1.1 yrs post-HTx (0.5–3.6 yrs). One pt has histologic CAD at 2 yrs post-HTx with normal clinical testing.
Conclusions: AMR occurs frequently after HTx in HLA sensitized pts. An algorithm of B cell-directed strategies pre and post-HTx can be effective in the management of these pts with reasonable intermediate term outcomes.