Dose-Dependent Response to Desensitization in Pediatric Heart Transplant Candidates Assessed by Single Antigen Bead Technology

Abstract

Purpose The efficacy of desensitization, the process of reducing anti-HLA antibodies in sensitized patients awaiting heart transplantation (HT), is unclear in pediatric HT candidates. Methods To evaluate the impact of DS in pediatric HT candidates, we performed a retrospective analysis of all patients listed for HT between 1/1/10 - 6/30/18 at our institution. Sensitized patients were defined as having a panel reactive antibody (PRA) ≥ 10% and ≥1 strong positive antibody with mean fluorescence intensity (MFI) ≥ 5500. Patients were identified as nonsensitized (NS, n = 55), sensitized but no therapy (S-NT, n = 18), and sensitized undergoing desensitization therapy (S-DS, n = 14). Response to desensitization was defined as ≥25% reduction in the MFI for ≥90% of strong positive antibodies for whom follow up PRA testing was performed prior to delisting, HT, or death (n = 13). Results DS consisted of IVIG and rituximab for all patients; 2 also received bortezomib. DS responders, defined by reduction in antibody burden (n = 8), received on average more doses of IVIG than nonresponders (9 vs 3, p = 0.04). All five S-DS patients that received HT during the study period had a negative flow crossmatch (FXM) and most (80%) would have had a positive FXM with historical serum. All S-DS had history of single ventricle congenital heart disease and homograft exposure. Prior VAD was associated with sensitization severity (mean positive antibodies 75 vs 26, p = 0.01) but not response to DS, and history of ECMO was associated with neither. S-DS compared S-NT were on average more sensitized (mean number of high MFI antibodies 45 vs 21, p = 0.04), waited longer for HT (569 vs 148 days, p = 0.005), and trended towards higher waitlist mortality (36% vs 11%, p = 0.09). NS patients were less likely to have homograft exposure (p Conclusion A favorable response to DS was observed in most patients in this cohort. Homograft and VAD, but not ECMO, were associated with severity of sensitization. IVIG appears to have some benefit, with a dose-dependent effect. Post-HT outcomes for S-DS, S-NT, and NS patients were similar in this study.