Outcomes in Patients with Acute Cellular Rejection Grade 1R: Is the Debate Over?
Recommended Citation
Lampert B, Williams C, Hernandez Montfort J, Kursel Obrien R, Aggarwal-Gupta C, Ravichandran A, Rao R, Campbell PT, Yaranov D, Carey S, Olymbios M, Armer-Cabral M, Zhang Z, Hall S. Outcomes in Patients with Acute Cellular Rejection Grade 1R: Is the Debate Over?. J Heart Lung Transplant 2024; 43(4):S377.
Document Type
Conference Proceeding
Publication Date
4-1-2024
Publication Title
J Heart Lung Transplant
Abstract
Purpose: Acute Cellular Rejection (ACR) grade 1R is usually untreated; however, recurrent 1Rs are associated with negative long-term outcomes. Donor-derived cell-free DNA (dd-cfDNA) is a biomarker for heart allograft injury and rejection. We hypothesize that ACR 1R concurrent with elevated dd-cfDNA may be indicative of clinically relevant rejection. We analyzed outcomes in an interim sub-analysis of patients with ACR 1R enrolled in the multicenter Prospera Test Evaluation in Cardiac Transplant (ProTECT) study, a registry of adult heart transplant (HTx) recipients in the US undergoing dd-cfDNA monitoring with the Prospera™ test (Natera, Austin, TX). Methods: Patients with biopsy-graded ACR 1R and a matched (i.e. within two weeks of biopsy) dd-cfDNA result were stratified by dd-cfDNA level: high (≥0.15%) and low (<0.15%). Time from ACR 1R diagnosis to the first instance of a composite endpoint (death, retransplantation, biopsy-proven rejection, treated rejection and graft dysfunction) was calculated. Kaplan-Meier curves were implemented using right-censoring techniques and differences in proportion of events between groups were assessed using Fisher's exact test. Results: Of the first 100 patients enrolled in ProTECT, 48 had an ACR 1R episode and matched dd-cfDNA result. The median follow-up time after the initial ACR 1R diagnosis was 10.4 mos (IQR: 7.3, 12.4 mos). 13/48 patients had a high dd-cfDNA result (median: 0.25%; IQR: 0.2%, 0.71%) and 35/48 had a low dd-cfDNA result (median: 0.04%; IQR: 0.02%, 0.07%). Significantly more of the high dd-cfDNA cohort (76.9%; [10/13]) met the composite endpoint than the low dd-cfDNA cohort (17.1% [6/35]; p<0.001; Figure 1). Conclusion: Elevated dd-cfDNA was associated with lower freedom from subsequent adverse outcomes in HTx recipients with an episode of ACR 1R. These findings suggest that not all ACR 1R cases are benign. More data are needed to validate these findings, however, the use of dd-cfDNA could help discern ACR 1R rejections needing closer monitoring or treatment. [Formula presented]
Volume
43
Issue
4
First Page
S377
