Recurrent acute cellular rejection graded ISHLT 1R early after heart transplantation negatively affects long-term outcomes: The prognostic significance of 1990 ISHLT grades 1B and 2

Peled, Yael; Lavee, Jacob; Ram, Eilon; Kassif, Yigal; Peled, Amir; Freimark, Dov; Ofek, Efrat; Kogan, Alexander

doi:10.1016/j.trim.2019.03.003

Cited by 13 publications

(17 citation statements)

References 24 publications

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“…In addition, when using the 0.32% DF cut-off value, the assay demonstrated 94.87% NPV and 43.90% PPV for grade 1R versus grade 0R, emphasizing the sensitivity of the DF determination to detect many cases of mild ACR. Sensitivity for ACR 1R may also reflect the fact that patients with recurrent rejection classified as 1R according to the 2004 ISHLT classification, which combines grades 1A, 1B, and 2 of the 1990 classification, have decreased freedom from late ACR and poorer long-term outcomes when of 1990 ISHLT 1B/2 histology [117,118]. Also of note, within this validation sample set, presence of coronary artery vasculopathy (CAV) correlated with increased DF [66].…”

Section: Clinical Performance Characteristics Of Mytai Heart Df As Anmentioning

confidence: 86%

Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: Validation of a rapid and highly sensitive clinical test for stratification of rejection probability

North

Ziegler²,

Mahnke³

et al. 2020

PLoS ONE

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Lifelong noninvasive rejection monitoring in heart transplant patients is a critical clinical need historically poorly met in adults and unavailable for children and infants. Cell-free DNA (cfDNA) donor-specific fraction (DF), a direct marker of selective donor organ injury, is a promising analytical target. Methodological differences in sample processing and DF determination profoundly affect quality and sensitivity of cfDNA analyses, requiring specialized optimization for low cfDNA levels typical of transplant patients. Using next-generation sequencing, we previously correlated elevated DF with acute cellular and antibody-mediated rejection (ACR and AMR) in pediatric and adult heart transplant patients. However, next-generation sequencing is limited by cost, TAT, and sensitivity, leading us to clinically validate a rapid, highly sensitive, quantitative genotyping test, myTAI HEART ® , addressing these limitations. To assure pre-analytical quality and consider interrelated cfDNA measures, plasma preparation was optimized and total cfDNA (TCF) concentration, DNA fragmentation, and DF quantification were validated in parallel for integration into myTAI HEART reporting. Analytical validations employed individual and reconstructed mixtures of human blood-derived genomic DNA (gDNA), cfDNA, and gDNA sheared to apoptotic length. Precision, linearity, and limits of blank/detection/quantification were established for TCF concentration, DNA fragmentation ratio, and DF determinations. For DF, multiplexed high-fidelity amplification followed by quantitative genotyping of 94 SNP targets was applied to 1168 samples to evaluate donor options in staged simulations, demonstrating DF call equivalency with/without donor genotype. Clinical validation studies using 158 matched endomyocardial

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Section: Clinical Performance Characteristics Of Mytai Heart Df As Anmentioning

confidence: 86%

Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: Validation of a rapid and highly sensitive clinical test for stratification of rejection probability

North

Ziegler²,

Mahnke³

et al. 2020

PLoS ONE

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“…The num-ber of treated rejection episodes within 1-year after HTx has been decreasing over time from nearly 25% in 2004-2006 to 12.6% in 2010-2016 [3]. Risk factors associated with developing rejection include female donor gender, recipient elevated BMI, and recurrent ACR grade 1R [24,36,116,117]. Factors not associated with increased rejection episodes include donor CPR status or history of cocaine use, and recipient history of prior sternotomy or prior MCS use (durable or temporary) [9,40,43,54].…”

Section: Rejection Of Allograftmentioning

confidence: 99%

Current status and outcomes in heart transplantation: a narrative review

Awad¹,

Shah²,

Griffith³

2022

Rev. Cardiovasc. Med.

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The first human heart transplantation was performed by Christian Barnard in 1967. While the technical aspect had been worked out, allograft rejection was a major limitation in the early days of heart transplant. The discovery of cyclosporine revolutionized the field and led to the modern era of transplant. Heart transplantation now offers the best survival benefit for patients with end-stage heart failure with a median survival over 12 years. However, there are still limitations including the impact of limited availability of graft, graft dysfunction, and rejection, and long-term non-cardiac complications. This review serves as an update on the short-and long-term outcomes following heart transplantation focusing on the new donor allocation system, efforts to expand the donor pool, primary graft dysfunction, acute cellular and antibody-mediated rejection, cardiac allograft vasculopathy, and post-transplant malignancy and renal dysfunction.

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“…Recurrent rejection in cardiac transplantation is associated with a poor prognosis. 41,42 Giunti et al 43 In one of the largest series, Kirklin et al 45 sought to determine whether ECP would prove beneficial in a high-risk group of patients.…”

Section: Ecp For Tre Atment Of Refr Ac Tory or Recurrent He Art Tr Ans Pl Ant Re Jec Tionmentioning

confidence: 99%

“…Recurrent rejection in cardiac transplantation is associated with a poor prognosis 41,42 . Giunti et al 43 investigated the effects of ECP in six heart transplant recipients with recurrent rejection.…”

Section: Ecp For Treatment Of Refractory or Recurrent Heart Transplant Rejectionmentioning

confidence: 99%

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment

Slomovich

Bell

Clerkin

et al. 2021

Clinical Transplantation

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Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

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Recurrent acute cellular rejection graded ISHLT 1R early after heart transplantation negatively affects long-term outcomes: The prognostic significance of 1990 ISHLT grades 1B and 2

Cited by 13 publications

References 24 publications

Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: Validation of a rapid and highly sensitive clinical test for stratification of rejection probability

Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: Validation of a rapid and highly sensitive clinical test for stratification of rejection probability

Current status and outcomes in heart transplantation: a narrative review

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment

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