TY - JOUR T1 - Cell-free DNA Tissues-of-Origin Profiling to Predict Graft versus Host Disease and Detect Infection after Hematopoietic Cell Transplantation JF - bioRxiv DO - 10.1101/2020.04.25.061580 SP - 2020.04.25.061580 AU - Alexandre Pellan Cheng AU - Matthew Pellan Cheng AU - Joan Sesing Lenz AU - Kaiwen Chen AU - Philip Burnham AU - Kaitlyn Marie Timblin AU - José Luis Orejas AU - Emily Silverman AU - Francisco M. Marty AU - Jerome Ritz AU - Iwijn De Vlaminck Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/29/2020.04.25.061580.abstract N2 - Allogeneic hematopoietic cell transplantation (HCT) provides effective treatment for hematologic malignancies and immune disorders. Monitoring for immune complications and infection is a critical component of post-HCT therapy, however, current diagnostic options are limited. Here, we propose a blood test that employs genome-wide profiling of methylation marks comprised within circulating cell-free DNA to trace the tissues-of-origin of cell-free DNA (cfDNA), to quantify tissue-specific injury, and to screen for microbial pathogens after allogeneic HCT. We applied this assay to 106 plasma samples collected from 18 HCT recipients at predetermined time points before and after allogeneic HCT. We observe marked dynamics in the composition and abundance of cfDNA from different tissues in response to conditioning chemotherapy and HCT. We find that the abundance of solid-organ derived cfDNA in the blood at one-month after HCT is an early predictor of acute graft-versus-host disease, a frequent immune-related complication of HCT that occurs when donor immune cells attack the patient’s own tissues (area under the curve, 0.9, p-value = 0.012). Metagenomic profiling of cfDNA was possible from the same assay and revealed the frequent occurrence of viral and bacterial infection in this patient population. This proof-of-principle study shows that cfDNA has the potential to improve the care of allogeneic HCT recipients by enabling earlier detection and better prediction of immune complications and infection after HCT.Competing Interest StatementThe authors have declared no competing interest. ER -