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Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients.

ABSTRACT: Donor-derived cell-free DNA (dd-cfDNA) has been of major interest recently as a non-invasive marker of graft injury, but has not yet been extensively tested in children. From May to September in 2019, a total of 76 pediatric patients receiving a liver graft were enrolled and there were 27 patients excluded. Ultimately plasma samples and matched liver specimens from 49 patients were successfully collected whenever rejection was suspected clinically. Dd-cfDNA were analyzed and then compared to biopsy. Of these, 11 (22.4%) patients were found to have rejection by biopsy. Dd-cfDNA levels were higher among patients with rejection compared to those with no rejection. In subgroup analysis, dd-cfDNA% among patients with rejection differed from those with EBV/CMV infection and DILI patients. Similarly, observations were available concerning dd-cfDNA (cp/mL). The AUC for dd-cfDNA% and dd-cfDNA (cp/mL) were 0.878, 0.841, respectively, both of which were higher than conventional LFTs. For rejection, dd-cfDNA% ??28.7% yielded a sensitivity of 72.7%, specificity 94.7% and dd-cfDNA (cp/mL) ??2076 cp/mL, yielded a sensitivity of 81.8%, specificity 81.9%. Of note, the dd-cfDNA distribution was significantly different between whole liver and LLS transplantation. In the setting of pediatric LTx, dd-cfDNA appears to be a sensitive biomarker indicating the presence of rejection.International Clinical Trails Registry Platform: ChiCTR1900022406.

SUBMITTER: Zhao D

PROVIDER: S-EPMC7807012 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients.

Zhao Dong D Zhou Tao T Luo Yi Y Wu Cheng C Xu Dongwei D Zhong Chengpeng C Cong Wenming W Liu Qiang Q Zhang Jianjun J Xia Qiang Q

Scientific reports 20210113 1

Donor-derived cell-free DNA (dd-cfDNA) has been of major interest recently as a non-invasive marker of graft injury, but has not yet been extensively tested in children. From May to September in 2019, a total of 76 pediatric patients receiving a liver graft were enrolled and there were 27 patients excluded. Ultimately plasma samples and matched liver specimens from 49 patients were successfully collected whenever rejection was suspected clinically. Dd-cfDNA were analyzed and then compared to bio ...[more]

PMID: 33441886

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Project description:AimsSome risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions.Methods and resultsWe performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1 year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other parameter (late transplant era) were statistically significant in predicting 1 year mortality. The initial score was generated by using the regression coefficients from the multivariable analysis as follows: 1.70 * ln age - 4.0 * ln height - 0.9 * diagnosis (= 1 if diagnosis = DCM) - 0.67 * diagnosis (= 1 if diagnosis = ICM) + 0.33 * ln total bilirubin + 1.74 * ln cold ischaemic time + 0.98 * mechanical circulatory support (MCS) implant (= 1 if MCS implant = ECMO) + 0.47 * MCS implant (= 1 of MCS implant = BVAD/TAH) - 0.66 * transplant era (= 1 if transplant era = 2017-2018). The initial score was converted into the Bad Oeynhausen (BO) score as a positive integer variable by means of the following formula: BO score = (initial score + 8) * 3. In patients scoring 2 to <7 points (n = 112), 7 to <11 points (n = 580), 11 to <15 points (n = 339), and 15 to 20 points (n = 18), 1 year survival was 93.1%, 84.2%, 66.9%, and 27.8%, respectively. The c-index of our score was 0.73 [95% confidence interval (CI): 0.69-0.77]. Values were in our cohort for the US and French scores 0.66 (95% CI: 0.62-0.70) and 0.63 (95% CI: 0.59-0.67), respectively.ConclusionsData indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.

Dataset Information

Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients.

Publications

Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients.

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