Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC-04 study

Abstract

Data on the clinical importance of newly detected donor-specific anti-HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One-third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first-year ndDSAs is being assessed in an extended cohort of patients.

Donor‐specific anti‐HLA antibody production following pediatric ABO‐incompatible heart transplantation

“…Studies in adults have shown that the presence of de novo DSAs can accelerate graft vasculopathy and decrease graft survival in heart and other solid organ transplants, with smaller studies in the pediatric heart transplant population yielding similar results . Our findings of more frequent rejection episodes in patients with newly detected DSAs are consistent with prior studies, including one that showed DSA‐positive pediatric cardiac transplant patients had 2.5 times more rejection events per year than DSA‐negative patients and a more recent study showing that newly detected DSAs in the first year post‐transplant are associated with more cellular rejection episodes . In one of the studies, patients with DSAs also had higher rates of CAV and decreased 5‐year graft survival .…”

“…21,22 Our findings of more frequent rejection episodes in patients with newly detected DSAs are consistent with prior studies, including one that showed DSA-positive pediatric cardiac transplant patients had 2.5 times more rejection events per year than DSA-negative patients and a more recent study showing that newly detected DSAs in the first year post-transplant are associated with more cellular rejection episodes. 24,26 In one of the studies, patients with DSAs also had higher rates of CAV and decreased 5-year graft survival. 24 Another study also showed that the appearance and persistence of de novo antibodies after the first year were associated with reduced graft and patient survival.…”

Six‐year experience with treatment of early donor‐specific anti‐HLA antibodies in pediatric lung transplantation using a human immunoglobulin‐based protocol

“…Thus, in most of the available studies, results were not reported separately for adult and pediatric patient . Evidence from pediatric kidney and heart transplantation showed that DSA is a risk factor for mortality and acute or chronic rejection . Dipchand et al have recently shown in a multicenter study including 237 pediatric heart‐transplant patients that one‐third of patients developed de novo DSA, usually within 6 weeks after transplantation, and that DSA were a risk factor for acute cellular rejection in the first year posttransplantation.…”

“…Evidence from pediatric kidney and heart transplantation showed that DSA is a risk factor for mortality and acute or chronic rejection . Dipchand et al have recently shown in a multicenter study including 237 pediatric heart‐transplant patients that one‐third of patients developed de novo DSA, usually within 6 weeks after transplantation, and that DSA were a risk factor for acute cellular rejection in the first year posttransplantation. Similarly, Irving et al showed that 40% of pediatric heart‐transplant patients developed de novo DSA and that patients with persistent vs. transient DSA showed an increased incidence of CAV, rejection and graft loss.…”

Hospital readmission following pediatric heart transplantation

“…Interestingly, in a prior analysis from our study we found that ventricular assist device (VAD) implantation was associated with a lower risk of developing newly detected donorspecific anti-HLA antibodies, suggesting the relationship of sensitizing events to outcomes in children may differ from that reported in adults. 9 When one examines readmission within 1 year of initial hospital discharge, there are several factors that are strongly associated with the incidence of readmission. A longer duration of initial hospital admission is associated with a higher readmission rate.…”