Cell-free DNA profiling informs all major complications of hematopoietic cell transplantation

Significance Hematopoietic cell transplantation is the gold standard treatment for many blood disorders, including blood cancers. Nonetheless, frequent post-transplant complications limit the long-term benefit of HCT. Here, we find that circulating cell-free DNA is a highly versatile analyte for monitoring of the most important complications of HCT: Graft-Versus-Host Disease, infection, graft failure and disease relapse. We show that these different therapeutic complications can be informed from a single cell-free DNA sequencing assay followed by disease-specific bioinformatic analyses. This test requires only low coverage DNA sequencing and is compatible with small volumes of blood. Cell-free DNA may improve the care of allogeneic HCT recipients by enabling earlier detection and better prediction of the complex array of complications that occur after HCT.