Cell-Free Dna As A Solid-Organ Transplant Biomarker: Technologies and Approaches

Edwards, R. A.; Menteer, Jondavid; Lestz, Rachel; Baxter‐Lowe, Lee Ann

doi:10.2217/bmm-2021-0968

Cited by 28 publications

(26 citation statements)

References 93 publications

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“…DF is expressed in percent, on the right lower Y-axis. Results of rd-cfDNA, dd-cfDNA and DF are based on three SNP [ 14 , 16 , 25 ], displayed as means. Results of cfDNA are the fluoroscopic measurements of patient plasma, expressed in ng/mL on the right upper Y-axis.…”

Section: Resultsmentioning

confidence: 99%

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study

Böhmer,

Wasslavik,

Andersson

et al. 2023

Transpl Int

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In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14 days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.

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Section: Resultsmentioning

confidence: 99%

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study

Böhmer,

Wasslavik,

Andersson

et al. 2023

Transpl Int

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“…1 Especially in the last few years, there has been an increasing interest in assessing the value of donor fraction cell-free DNA (df-cfDNA) in diagnosis of acute rejection in heart transplant recipients. 1,2 Two major initiatives from NHLBI focused on the development of cfDNA assays have been undertaken, one with adult heart transplant recipients and the other in a combined cohort of pediatric and adult patients. The NHLBI sponsored Genomic Research Alliance for Transplantation (GRAfT) study analyzed the differences between the donor and the recipient across SNPs to quantify donor derived cfDNA.…”

Section: Backg Rou N Dmentioning

confidence: 99%

“…Non‐invasive surveillance for rejection has been an ongoing area of significant research and development over the last decade 1 . Especially in the last few years, there has been an increasing interest in assessing the value of donor fraction cell‐free DNA (df‐cfDNA) in diagnosis of acute rejection in heart transplant recipients 1,2 …”

Section: Introductionmentioning

confidence: 99%

Evaluating threshold for donor fraction cell‐free DNA using clinically available assay for rejection in pediatric and adult heart transplantation

Deshpande,

Zangwill,

Richmond

et al. 2024

Pediatric Transplantation

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BackgroundThe aims of the study were to assess the performance of a clinically available cell‐free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection.MethodsObservational, non‐interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy‐associated plasma samples were used for cfDNA measurements. Pre‐determined cut points were tested for analytic performance.ResultsA total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df‐cfDNA values between rejection [0.21% (IQR 0.12–0.69)] and healthy samples [0.05% (IQR 0.01–0.14), p < .0001]. The pediatric rejection group had a median df‐cfDNA value of 0.93% (IQR 0.28–2.84) compared to 0.09% (IQR 0.04–0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection.ConclusionThe study suggests that pediatric patients with rejection show higher levels of circulating df‐cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

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“…There are no data on the use of dd-cfDNA in multiorgan transplant recipients. DD-cfDNA quantification may prove to be valuable, but combining dd-cfDNA with other biomarkers will improve the diagnostic potential [ 78 ]. Post-transplant monitoring requires high-quality biomarkers for early detection of graft damage or rejection and early therapeutic intervention.…”

Section: Limitationsmentioning

confidence: 99%

Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

et al. 2023

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A number types of extracellular DNA (eg, cell-free, cfDNA) circulate in human blood, including mitochondrial, transcriptome, and regulatory DNA, usually at low concentrations. Larger amounts of cfDNA appear in any inflammatory condition, including organ damage due to a variety of reasons. The role of cfDNA in solid organ transplantation is discussed in this review as a valuable additional tool in the standard of care of transplant patients. Post-transplant monitoring requires the use of high-quality biomarkers for early detection of graft damage or rejection to be able to apply early therapeutic intervention. CfDNA complements the traditional monitoring strategies, being a risk stratification tool and an important prognostic marker. However, improving the sensitivity and specificity of cfDNA detection is necessary to facilitate personalized patient management, warranting further research in terms of measurement, test standardization, and storage, processing, and shipping. A diagnostic test (Allosure, CareDx, Inc., Brisbane, CA) for kidney, heart and lung transplant patients is now commercially available, and validation for other organs (eg, liver) is pending. To date, donor-derived cfDNA in combination with other biomarkers appears to be a promising tool in graft rejection as it is minimally invasive, time-sensitive, and cost-effective. However, improvement of sensitivity and specificity is required to facilitate personalized patient management. Whether it could be an alternate to graft biopsy remains unclear.

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Cell-Free Dna As A Solid-Organ Transplant Biomarker: Technologies and Approaches

Cited by 28 publications

References 93 publications

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study

Evaluating threshold for donor fraction cell‐free DNA using clinically available assay for rejection in pediatric and adult heart transplantation

Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

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