Abstract
Background: The 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. Methods: Observational, 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. Results: A 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. Conclusion: The 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.
| Original language | English (US) |
|---|---|
| Article number | e14708 |
| Journal | Pediatric transplantation |
| Volume | 28 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 2024 |
Funding
The authors thank the DNA-Based Transplant Rejection Test (DTRT) study coordinators for collecting and shipping thousands of samples and for their tremendous administrative and regulatory support: Columbia University, Andres Gomez, Arielle Repp; Duke University, Angel Barnes, Sarah Casalinova; Emory University and Children's Healthcare of Atlanta, Susie Gentry, Raejanna Ashley, Jack Goldberg; Vanderbilt University, Jill Janssen, Ellie Dahms, Alexandria Manis, Alesia Pruitt; University of Arkansas, Denise Graves, Grace Goode, Sheila Stroupe; Children's Wisconsin, Gail Stendahl, Julie Schmidt, Alyssa Pollow, Jen Yauck; MCW and Froedtert Hospital, Mary Wexler, Sue Cotey, Heidi Martin, Janet Gosset; Lurie Children's Hospital of Chicago, Kathleen Van't Hof, Eniola Oke, Kristina Stevanovic, Paul Haschke and Avaliese Porlier. The authors also thank study team members from TAI Diagnostics, CAN AM, MCW/CW and Natera Inc. for running samples, quality assurance, regulatory support, core support, and data monitoring: Mary Goestch, Huan ling Liang, Mary Krolikowski, Alexis Sullivan, Don Johnsen, Michelle Otto, Ernest Allen, Pam Baker, Sandy Miller, Sharon Rabine, Michelle Ariston, Sarah McCormick, and Anne Laulederkind. This work was funded by a grant from the National Institutes of Health (5R01HL119747), TAI Diagnostics Inc. through an NIH-approved third-party agreement and Natera Inc. No funding organization had any role in the interpretation or analysis of data, and none provided any input or had any right to influence or authorize publication or modification of this manuscript. All analyses, results, conclusions, presentations and publications related to this study are reviewed and approved by the NIH-mandated DTRT steering committee consisting of representative members from all the clinical study sites. The authors thank the DNA\u2010Based Transplant Rejection Test (DTRT) study coordinators for collecting and shipping thousands of samples and for their tremendous administrative and regulatory support: Columbia University, Andres Gomez, Arielle Repp; Duke University, Angel Barnes, Sarah Casalinova; Emory University and Children's Healthcare of Atlanta, Susie Gentry, Raejanna Ashley, Jack Goldberg; Vanderbilt University, Jill Janssen, Ellie Dahms, Alexandria Manis, Alesia Pruitt; University of Arkansas, Denise Graves, Grace Goode, Sheila Stroupe; Children's Wisconsin, Gail Stendahl, Julie Schmidt, Alyssa Pollow, Jen Yauck; MCW and Froedtert Hospital, Mary Wexler, Sue Cotey, Heidi Martin, Janet Gosset; Lurie Children's Hospital of Chicago, Kathleen Van't Hof, Eniola Oke, Kristina Stevanovic, Paul Haschke and Avaliese Porlier. The authors also thank study team members from TAI Diagnostics, CAN AM, MCW/CW and Natera Inc. for running samples, quality assurance, regulatory support, core support, and data monitoring: Mary Goestch, Huan ling Liang, Mary Krolikowski, Alexis Sullivan, Don Johnsen, Michelle Otto, Ernest Allen, Pam Baker, Sandy Miller, Sharon Rabine, Michelle Ariston, Sarah McCormick, and Anne Laulederkind. This work was funded by a grant from the National Institutes of Health (5R01HL119747), TAI Diagnostics Inc. through an NIH\u2010approved third\u2010party agreement and Natera Inc. No funding organization had any role in the interpretation or analysis of data, and none provided any input or had any right to influence or authorize publication or modification of this manuscript. All analyses, results, conclusions, presentations and publications related to this study are reviewed and approved by the NIH\u2010mandated DTRT steering committee consisting of representative members from all the clinical study sites.
Keywords
- acute rejection
- antibody mediated rejection
- cell-free DNA
- heart transplant
- pediatric heart transplant
- screening
- surveillance
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Transplantation
