P122. Complete Blood Cell Differential as a Screening Biomarker for Post-transplant Rejection

McCormick Place Lakeside Center  

Objective
Non-invasive rejection monitoring using HeartCare, a combination of gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cf-DNA), has proven useful as an alternative to post-transplant biopsy. However, limited accessibility prevents its standard application. Conversely, complete blood cell ratios (CBRs) are derived from routine CBC differentials (CBCD) and have demonstrated capabilities in predicting heart transplant rejection. This study aimed to evaluate the relationship between HeartCare and myocardial biopsy results with components of a routine CBCD.
Methods
We enrolled 33 of 34 patients (female n=9; 32±17 years old; 12.2 tests/patient) registered in the SHORE (Surveillance HeartCare Outcomes) Registry who received regular HeartCare follow-up and had a negative prospective crossmatch. The relationship between five immediate pre-test CBCD components (neutrophil, lymphocyte, monocyte, neutrophil-lymphocyte ratio [NLR], and lymphocyte-monocyte ratio [LMR]) and HeartCare positivity (defined as GEP ≥34 and dd-cf-DNA ≥0.2) was analyzed across 407 tests using a Linear Mixed-Effect Model. The cut-off value of the resulting variable was then validated against mild or greater rejection using a generalized linear mixed model, incorporating 373 post-transplant myocardial biopsy results from the same patients.
Results
The study population consisted of 29 White, 1 Black, 2 Asian, and 1 other patient. Heart transplant status at transplantation was status 1 (1), status 2 (8), status 3 (11), status 4 (9), and status 6 (4). HeartCare positivity was observed in 46 tests. LMR showed the strongest association with HeartCare positivity (p=0.006, R²=0.45), followed by lymphocyte (p=0.002, R²=0.40) and NLR (p=0.03, R²=0.26). The cut-off for LMR to prompt consideration of HeartCare was calculated from the ROC curve. An LMR of 2.00 yielded a sensitivity of 91% and specificity of 63%. These 33 patients underwent 373 biopsies including 88, 5, and 2 patients with grade 1, 2, and 3 cellular rejection, respectively. An LMR cut-off of 2.0 was significantly associated with higher odds of mild or greater cellular rejection (OR 2.32 [1.33-4.00], p=0.003).
Conclusion
These results demonstrate a novel application of LMR as a highly accessible biomarker strongly associated with combined GEP and dd-cf-DNA rejection monitoring and myocardial biopsy results. LMR may aid in guiding decisions regarding HeartCare testing, biopsy, and immunosuppression treatment.

Authors
Isaac Knouff (1), Tomoki Sakata (2), Maika Schneider (3), Ioannis Dimarakis (1), richard cheng (2), April Stempien-Otero (2), Jay Pal (2)
Institutions
(1) University of Washington School of Medicine, Seattle, WA, (2) University of Washington Medical Center, Seattle, WA, (3) University of Washington, Seattle, WA

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Innovations: New devices or novel approaches, preclinical or clinical