Donor fraction cell-free DNA and rejection in adult and pediatric heart transplantation

Richmond, Marc E.; Zangwill, Steven; Kindel, Steven J.; Deshpande, Shriprasad; Schroder, Jacob N.; Bichell, David P.; Knecht, Kenneth R.; Mahle, William T.; Wigger, M.; Gaglianello, Nunzio; Pahl, Elfriede; Simpson, Pippa; Dasgupta, Mahua; North, Paula E.; Hidestrand, Mats; Tomita‐Mitchell, Aoy; Mitchell, Michael E.

doi:10.1016/j.healun.2019.11.015

Cited by 70 publications

(88 citation statements)

References 16 publications

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“…Sayah et al analyzed lung transplant patients and suggested that dd-cfDNAsensitivity was 73.1%, whereas its specificity was 52.9% [31]. Furthermore, in heart transplants, a diagnosis can be predicted with 92% sensitivity and 75% specificity [32]. By assessing donor-derived cell-free DNA in a kidney transplant, Huang et al observed that a kidney injury can be detected with 100% sensitivity and 71.8% specificity.…”

Section: Discussionmentioning

confidence: 99%

Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials

Stawski

Stec-Martyna

Chmielecki

et al. 2021

Biology

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We aimed to summarize the current knowledge about the trends in cfDNA application based on the analysis of clinical trials registered until April 2021. International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov were searched with the keywords: “cf-DNA”; “Circulating DNA”; “Deoxyribonucleic Acid”; and “Cell-Free Deoxyribonucleic Acid”. Of 605 clinical trials, we excluded 237 trials, and 368 remaining ones were subject to further analysis. The subject, number of participants, and study design were analyzed. Our scoping review revealed three main trends: oncology (n = 255), non-invasive prenatal diagnostic (n = 48), and organ transplantation (n = 41), and many (n = 22) less common such as sepsis, sport, or autoimmune diseases in 368 clinical trials. Clinical trials are translating theory into clinical care. However, the diagnostic value of cfDNA remains controversial, and diagnostic accuracy still needs to be evaluated. Thus, further studies are necessary until cfDNA turns into a standard in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials

Stawski

Stec-Martyna

Chmielecki

et al. 2021

Biology

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“…Per UNOS, the 2019 1-year survival after lung transplantation is nearly 90%, and this may be partly attributed to advancements in organ procurement, 10 mechanical circulatory support device usage, 10 improved organ rejection surveillance 12 , and newer immunosuppressive agents. 13 However, amongst the overall improved survival rates of the modern era, we have unmasked that survival in patients over 70 is inferior to those 60-69. Since the Cooper et al study in 2015, the number of patients who have undergone heart transplantation has nearly doubled.…”

Section: Discussionmentioning

confidence: 99%

Modern UNOS Data Reveals Septuagenarians have Inferior Heart Transplant Survival

Suryapalam

Kanaparthi

Kashem

et al. 2021

Preprint

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Background: While heart transplantation is increasingly performed in the United States for elderly patients, survival outcomes have primarily been analyzed in single-center studies. The few existing long-term studies have indicated no difference in HTx outcomes between patients ≥70 years and 60-69 years age, but these studies only assessed to 5-years post-transplant and included data from the 1980-90s, introducing significant variance due to poorer outcomes in that era. We analyzed the UNOS database from 1987-2020, stratified by timeframe at 2000, to derive a more representative comparison of modern HTx survival outcomes. Methods: All UNOS HTx recipients over 18 years of age (n=66,186) were divided into 3 cohorts: 18-59, 60-69 and ≥70 years old. Demographic data as well as perioperative factors were evaluated for significance using Chi-Squared and H-Tests as appropriate. Kaplan-Meier Curve and cox regressions with log-rank tests were used to assess 5 through 10 year survival outcomes. Results: 45,748 were 18-59 years old, 19,129 were 60-69 years old and 1,309 were ≥70 year old. The distribution of most demographic and perioperative factors significantly differed between cohorts. Pairwise survival analysis involving the 18-59 cohort always indicated significance. While there was no significance between the two older cohorts in the earlier timeframe, there was significance in the later timeframe from 6-10 years post-HTx (p<0.05). Cox regressions confirmed results. Conclusions: The results indicate that since 2000, recipients 60-69 years of age have better 6 through 10-year post-transplant survival than older recipients, a relationship previously obscured by worse outcomes in early data.

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“…In terms of AMR, there is a significant rise in dd-cfDNA with pAMR 1 and higher grades of rejection. 27 Patterns of dd-cfDNA elevation also differ in AMR as compared with ACR, which may help facilitate diagnosis. Agbor-Enoh et al found that, for similar histopathologic grades, the percent dd-cfDNA was higher in AMR as compared with ACR, rose preceding the histologic diagnosis, and had a distinct fragment length with shorter fragments of cfDNA.…”

Section: Cell-free Dnamentioning

confidence: 99%