Antibody Mediated Rejection in Pediatric Heart Transplantation: Should We Re-Biopsy Sooner or Later?

Abstract

<h3>Purpose</h3> The intent of this study was to examine if there are any factors associated with clearance of antibody mediated rejection (AMR) and to identify the optimal time for follow up biopsy after a diagnosis of AMR. <h3>Methods</h3> A retrospective single-center cohort analysis of patients < 18 years of age who underwent heart transplant (HTx) between 08/2013 - 9/2021 was performed. AMR was defined as positive C4d on endomyocardial right ventricular biopsy (EMB). Concurrent ACR was recorded. Time until clearance was measured in days until follow up EMB was C4d negative. The number of biopsies performed until clearance was also recorded to account for clinical variation in timing for follow up biopsies. <h3>Results</h3> Thirty-five unique patients developed AMR with a total of 41 unique episodes of AMR. All patients received pulse steroids. Additional treatments included IVIG, rituximab, daratumumab, eculizumab, and plasmapheresis, depending on the degree of illness and persistence of AMR. The cohort was 62% male, 27% non-Hispanic White, 51% Hispanic, 20% non-Hispanic Black, and 2% Other. Median age at HTx was 4.6 years (IQR 0 - 12.3), and median days from HTx until AMR was 80 days (IQR 16 - 765 days). The median duration to clear AMR was 28 days (IQR: 17 - 56), 56% of AMR episodes cleared on the first biopsy; and the mean number of biopsies to clear AMR was 1.8. AMR did not resolve in 10% (4/41). Patients with unresolved AMR tended to have a history of prior AMR (50% vs 11%, p = 0.095) and be older at HTx (median age 15yrs, IQR 12.5 - 17.1 vs median 4.3yr, IQR 0.7 to 11.4 yrs, p = 0.01). Analyzing those who had resolution of AMR, there was no association of sex, age at HTx or time since HTx with time to resolution. Those with recurrent AMR took longer to resolve (median 162 days vs 28 days, p = 0.01). Patients with concurrent ACR had a shorter time to AMR resolution (median 16 days vs 33 days, p = 0.01). <h3>Conclusion</h3> There does not appear to be an association between time to clear AMR with patient demographics or time after transplant of the index case of AMR. Patients with prior resolved AMR take longer to clear recurrent cases of AMR. Concurrent ACR was associated with quicker time to clear AMR for reasons that remain unclear. The optimal time period to reassess for AMR clearance, based on this single-center data, is 1 month.