Key result
In 13 highly sensitized pediatric heart transplant recipients managed with B-cell directed therapies, antibody-mediated rejection occurred in 69% and acute cellular rejection in 54%, with 4 deaths.
Cohort (n=13)
Despite frequent early acute cellular and antibody-mediated rejection, a B cell-directed management strategy can yield reasonable intermediate-term outcomes in highly HLA-sensitized pediatric heart transplant recipients.
Answers are grounded in this paper and cite their sources.
High rejection rates despite B-cell therapy in this small series caution against routine adoption; leaves open efficacy in sensitized pediatric heart recipients.
BACKGROUND: There is an elevated risk for poor outcomes after heart transplant (HTx) in patients sensitized to human leukocyte antigens including graft dysfunction, acute cellular and antibody-mediated (AMR) rejection, and cardiac allograft vasculopathy. We report our experience with human leukocyte antigens-sensitized pediatric HTx recipients. METHODS AND RESULTS: We identified pediatric HTx patients with elevated pre-HTx Panel Reactive Antibody (Class I/II; > 10%), or a positive T- or B-cell crossmatch. Thirteen patients met criteria (5 female, 39%). The median age at HTx was 7 months (3.5 months to 15.5 years). Nine were infants who had prior palliation for congenital heart disease. Four were older patients (median 7.3 years; 4.8 to 15.5 years): 2 had congenital heart disease (Fontan), 2 were re-HTx. B-cell therapies were used in all patients, guided by assessment of CD19+ and CD20+ cells. Immunosuppression included thymoglobulin induction, and tacrolimus, mycophenolate mofetil, and steroids. Daily plasmapheresis +/- intravenous immunoglobulin G was used if there was a positive crossmatch on day 1, with a gradual, biopsy-guided weaning schedule. Rituximab was used when AMR was detected on biopsy: more recently (n=3), used empirically perioperatively. AMR was confirmed in 9 patients within median 0.9 months post-HTx. Seven had early acute cellular rejection (> or = ISHLT Grade 2 R) with no hemodynamic compromise or graft dysfunction. There were 4 deaths post-HTx (range, 11 days to 9 months). The median follow-up of 9 survivors was 1.7 years (0.3 to 3.7 years). Of 7 patients > 6 months post-HTx, no AMR or cardiac allograft vasculopathy was observed at a mean of 1.9+1.1 years post-HTx and no cardiac allograft vasculopathy. CONCLUSIONS: Despite aggressive management, acute cellular rejection and AMR occurred frequently early post-HTx. An algorithm of B cell-directed strategies can be effective in managing these patients with reasonable intermediate-term outcomes.
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Pollock‐BarZiv et al. (2007) conducted a cohort in Pediatric heart transplantation in HLA-sensitized patients (n=13). B-cell directed therapies and aggressive immunosuppression was evaluated on Antibody-mediated rejection (AMR). In 13 highly sensitized pediatric heart transplant recipients managed with B-cell directed therapies, antibody-mediated rejection occurred in 69% and acute cellular rejection in 54%, with 4 deaths.
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