Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

Autor: Deshpande SR; Division of Pediatric Cardiology, Children's National Heart Institute, Children's National Hospital, Washington, District of Columbia, USA., Zangwill SD; Division of Cardiology, Phoenix Children's Hospital, Phoenix, Arizona, USA., Kindel SJ; Division of Pediatric Cardiology, Department of Pediatrics, Medical College of Wisconsin, Herma Heart Institute, Children's Wisconsin, Milwaukee, Wisconsin, USA., Schroder JN; Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University, Durham, North Carolina, USA., Bichell DP; Division of Pediatric Cardiac Surgery, Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA., Wigger MA; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Richmond ME; Department of Pediatrics, Division of Pediatric Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA., Knecht KR; Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas, USA., Pahl E; Emeritus of Pediatrics, Cardiology, Lurie Children's Hospital, Chicago, Illinois, USA., Gaglianello NA; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Mahle WT; Division of Cardiology, Department of Pediatrics, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia, USA., Stamm KD; Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Simpson PM; Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Dasgupta M; Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Zhang L; Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., North PE; Department of Pathology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA., Tomita-Mitchell A; Division of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Milwaukee, Wisconsin, USA., Mitchell ME; Division of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Children's Wisconsin, Milwaukee, Wisconsin, USA.
Jazyk: angličtina
Zdroj: Pediatric transplantation [Pediatr Transplant] 2022 Jun; Vol. 26 (4), pp. e14264. Date of Electronic Publication: 2022 Mar 08.
DOI: 10.1111/petr.14264
Abstrakt: Background: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest.
Methods: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA.
Results: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001).
Conclusion: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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