Transplant Trial Watch

Donor-specific Cell-Free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review.

Knight SR, Thorne A, Faro MLL.

Transplantation, 2018; 103(2):273-283.

To examine the techniques and evidence for the relationship between donor-derived cell-free DNA (dd-cfDNA) levels and clinical outcomes in solid organ transplant recipients.

A systematic literature search was performed in OVID MEDLINE, EMBASE, the Transplant Library and the Cochrane Library. Reference lists of included studies and relevant reviews were screened. Unpublished and ongoing studies were also identified. Titles, abstracts and full text were assessed by two reviewers to confirm inclusion; differences were resolved by review and discussion. Risk of bias was assessed. All studies that reported dd-cfDNA levels in the urine or plasma of adult or pediatric solid organ transplant recipients and related these levels to 1 or more transplant-related outcomes were eligible for inclusion. No restrictions were placed on study design, publication language or date.

95 manuscripts/abstracts from 47 studies met the inclusion criteria; 24 studies were reported in abstract form only. One study was a report of a single case, the rest were retrospective (n=17) and prospective (n=29) cohort studies. Transplant types were kidney (n=18), liver (n=7), heart (n=11), kidney-pancreas (n=1), lung (n=5) and multiple types (n=5). Searches identified 6 ongoing studies.

Study-level data was extracted. Data relating dd-cfDNA to clinical outcomes were identified as acute rejection, other transplant related outcomes and response to treatment. Studies that compared the diagnostic accuracy of dd-cfDNA to other markers were also identified. The findings are reported as a narrative review as meta-analysis was not possible due to study heterogeneity and poor quality.

To search date (June 12th 2018).

CET Conclusions
The systematic review aims to study techniques and evidence for the relationship between donor-derived cell-free DNA levels (dd-cfDNA) and clinical outcomes in adult and paediatric solid organ transplant recipients. The review was prospectively registered with PROSPERO. A comprehensive bibliographic search was conducted and in addition trial registries were searched to identify unpublished or ongoing studies. Study eligibility, data extraction and assessment of the risk of bias (QUADAS-2 tool) was performed by two independent reviewers. Forty-seven studies were included of which 24 were congress abstracts. Because of the heterogeneity among studies and low study quality, findings were reported in a narrative review. The authors concluded that there is evidence for the validity of using dd-cfDNA as a biomarker in solid organ transplantation. Studies show a strong relationship between dd-cfDNA and acute rejection and other causes of acute allograft injury.

Quality notes
Quality assessment not appropriate

Trial registration
PROSPERO - CRD42017082273

Funding source
No funding received