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Tissue Transplantation

Tissue Transplantation

Tissue transplantation is a significant medical procedure involving the transfer of cells, tissues, or organs from a donor to a recipient, with the primary aim of restoring lost functions. This procedure is crucial in treating a broad spectrum of diseases, including kidney diseases, liver failure, heart disease, and certain types of cancers.
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...

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Detection of Residual Donor Erythroid Progenitor Cells after Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies

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A two-threshold donor-derived cell-free DNA algorithm improves detection of molecular rejection in heart

Dr Philip F Halloran¹, Katelynn S Madill-Thomsen¹, D Giovanni Biagini²

¹University of Alberta, Edmonton, Alberta, Canada.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation

|June 22, 2026

Summary

Donor-derived cell-free DNA (dd-cfDNA) with a two-threshold algorithm (2TA) improves heart transplant rejection detection. This method enhances specificity and AUC, outperforming previous cutoffs and histologic assessments for molecular rejection.

Keywords:

antibody mediated rejection donor quantity score donor-derived cell-free DNA%endomyocardial biopsy heart transplant

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Last Updated: Jun 24, 2026

Detection of Residual Donor Erythroid Progenitor Cells after Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies

Detection of Residual Donor Erythroid Progenitor Cells after Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies

Published on: September 6, 2017

Measurement of T Cell Alloreactivity Using Imaging Flow Cytometry

Measurement of T Cell Alloreactivity Using Imaging Flow Cytometry

Published on: April 19, 2017

Area of Science:

Transplantation Immunology
Biomarker Discovery
Molecular Diagnostics

Background:

Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for heart allograft rejection.
A two-threshold algorithm (2TA) was developed using dd-cfDNA percentage and donor-quantity score (DQS) for rejection risk assessment.
The performance of 2TA in detecting molecular rejection was evaluated using the Molecular Microscope® Diagnostic System (MMDx).

Purpose of the Study:

To evaluate the performance of the two-threshold algorithm (2TA) for detecting molecular rejection in heart transplant recipients.
To compare the diagnostic accuracy of 2TA with previous dd-cfDNA cutoffs and histologic assessment.
To assess the predictive value of dd-cfDNA percentage and DQS for MMDx-classified rejection.

Main Methods:

Analysis of endomyocardial biopsies and matched dd-cfDNA assessments from the prospective Trifecta-Heart study.
Classification of biopsies as rejection or no rejection using the Molecular Microscope® Diagnostic System (MMDx).
Application of the two-threshold algorithm (2TA) incorporating dd-cfDNA percentage and donor-quantity score (DQS).

Main Results:

Among 366 biopsy-matched samples, MMDx identified 108 cases of rejection.
Median dd-cfDNA% and DQS were significantly higher in rejection versus non-rejection groups (p<0.001).
2TA demonstrated higher specificity (83.7%) and similar sensitivity (83.3%) compared to the previous 0.15% dd-cfDNA cutoff, reducing false positives by 30% (AUC 0.87).

Conclusions:

The two-threshold algorithm (2TA) using dd-cfDNA percentage and DQS improves specificity and AUC for heart transplant rejection detection.
2TA predicts molecular rejection more effectively than histologic rejection assessment.
Increased dd-cfDNA% and DQS are significantly associated with higher odds of MMDx-classified rejection.