A Positive CDC T-cell Crossmatch is Strongly Associated with Allograft Loss and Early Rejection in Pediatric Heart Transplant Recipients

Abstract

<h3>Purpose</h3> A recent multi-center study (CTOT-04) reported similar first year outcomes in children with CDC T-cell crossmatch (XM) + and XM- heart transplant (HT) but was underpowered and had only 11 children in the CDC+ HT group. We assessed the association of donor specific T-cell CDC and Flow XM HT with the risk of rejection and allograft loss in US pediatric recipients over 20 years. <h3>Methods</h3> We queried the OPTN database for all pediatric HT performed between 1999 and 2019. Donor specific T-cell XM results were categorized as CDC+, Flow+/CDC Unknown, Flow+/CDC-, and Flow-. Covariate adjustment using a propensity score balanced risk factors between the XM+ and XM- groups. <h3>Results</h3> Of 4695 pediatric HT, there were 165 CDC+, 288 Flow+/CDC Unknown, 94 Flow+/CDC-, and 4148 Flow- recipients. The median age at HT was 7 years, 44% female, 55% white, and 44% had a pre-HT diagnosis of CHD. Pre-HT diagnosis, hemodynamic support, and year of heart transplant differed between the XM+ and XM- groups prior to propensity score adjustment. After adjusting for propensity score, children with a CDC+ HT were significantly more likely to lose their allograft or develop rejection requiring treatment in the first post-HT year (<b>Table</b>). Propensity score matching and stratification by propensity score quintile demonstrated similar results. Over the period of the study, there was a significant shift in the type of XM assays performed (1999: 90% of HT with CDC XM, 32% Flow XM; 2019: 28% of HT with CDC XM, 87% Flow XM). <h3>Conclusion</h3> Children receiving a CDC+ XM HT are at higher risk of graft loss and rejection during the first post-transplant year, suggesting higher anti-HLA antibody burden in such recipients. The lack of differences in allograft loss and rejection with a positive Flow XM alone may be due to current treatment strategies. The shift away from performing a CDC XM results in a loss of important prognostic information. Prospective clinical trials of donor acceptance and antibody treatment strategies are needed.