{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:12:33Z","timestamp":1785233553053,"version":"3.55.0"},"posted":{"date-parts":[[2024,5,16]]},"group-title":"Genetic and Genomic Medicine","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Despite long-standing success of hematopoietic stem cell transplantation (HSCT) in the treatment of blood cancers and severe immune disorders, monitoring post-transplant complications remains challenging, in part because of the limited availability of informative molecular tests. Here, we evaluated the utility of cell-free RNA (cfRNA) in plasma as an analyte to monitor HSCT recipients and predict immune-related complications. We used RNA-sequencing to profile cfRNA in 549 plasma samples collected at predetermined time points from allogeneic HSCT recipients at two transplant centers. We found that cfRNA temporal profiles in recipients with a complication-free course follow a relatively uniform trajectory, whereas recipients who experience complications exhibit divergent trajectories. cfRNA patterns also differed greatly from circulating cell counts, providing complementary information on cell expansion and turnover. We also used cfRNA profiles at early time points to train machine learning models for the early prediction of acute GVHD, chronic and late acute GVHD, and the outcome of immunosuppression taper. We discovered shared signatures that achieved good performance across different scenarios in both cohorts. Overall, our findings provide support for the use of plasma cfRNA profiling to monitor immune related complications of HSCT.<\/jats:p>","DOI":"10.1101\/2024.05.15.24307448","type":"posted-content","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:45:15Z","timestamp":1715906715000},"source":"Crossref","is-referenced-by-count":5,"title":["Plasma Cell-Free RNA Captures Immune Dynamics and Predicts GVHD after Hematopoietic Stem Cell Transplantation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8816-4293","authenticated-orcid":false,"given":"Conor","family":"Loy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glory","family":"Agun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel H.","family":"Gonzalez-Bocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Lenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Belcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bliss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eweis-LaBolle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3369-6692","authenticated-orcid":false,"given":"Tinyi","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Pidala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-4669","authenticated-orcid":false,"given":"Jerome","family":"Ritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-7311","authenticated-orcid":false,"given":"Iwijn","family":"De Vlaminck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025042023500460000_2024.05.15.24307448v2.1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-0301"},{"key":"2025042023500460000_2024.05.15.24307448v2.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197905103001902"},{"key":"2025042023500460000_2024.05.15.24307448v2.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.3.555.555"},{"key":"2025042023500460000_2024.05.15.24307448v2.4","doi-asserted-by":"crossref","first-page":"569381","DOI":"10.3389\/fimmu.2020.569381","article-title":"Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications","volume":"11","year":"2021","journal-title":"Front. Immunol"},{"key":"2025042023500460000_2024.05.15.24307448v2.5","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s12185-022-03416-7","article-title":"Relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia: an overview of prevention and treatment","volume":"116","year":"2022","journal-title":"Int J Hematol"},{"key":"2025042023500460000_2024.05.15.24307448v2.6","doi-asserted-by":"crossref","unstructured":"C. McDonald-Hyman , L. A. Turka , B. R. Blazar , Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Sci. Transl. Med. 7 (2015).","DOI":"10.1126\/scitranslmed.aaa6853"},{"key":"2025042023500460000_2024.05.15.24307448v2.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337"},{"key":"2025042023500460000_2024.05.15.24307448v2.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.12.001"},{"key":"2025042023500460000_2024.05.15.24307448v2.9","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1182\/blood.2023022735","article-title":"Chronic graft-versus-host disease: unresolved complication or ancient history?","volume":"144","year":"2024","journal-title":"Blood"},{"key":"2025042023500460000_2024.05.15.24307448v2.10","doi-asserted-by":"crossref","first-page":"e149296","DOI":"10.1172\/JCI149296","article-title":"Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease","volume":"131","year":"2021","journal-title":"Journal of Clinical Investigation"},{"key":"2025042023500460000_2024.05.15.24307448v2.11","doi-asserted-by":"crossref","first-page":"327","DOI":"10.4103\/0971-3026.143895","article-title":"Imaging of complications from hematopoietic stem cell transplant","volume":"24","year":"2014","journal-title":"Indian Journal of Radiology and Imaging"},{"key":"2025042023500460000_2024.05.15.24307448v2.12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-564997"},{"key":"2025042023500460000_2024.05.15.24307448v2.13","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020214"},{"key":"2025042023500460000_2024.05.15.24307448v2.14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-08-355990"},{"key":"2025042023500460000_2024.05.15.24307448v2.15","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1182\/blood.2019000953","article-title":"Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease","volume":"136","year":"2020","journal-title":"Blood"},{"key":"2025042023500460000_2024.05.15.24307448v2.16","doi-asserted-by":"crossref","unstructured":"C. Loy , L. Ahmann , I. De Vlaminck , W. Gu , Liquid Biopsy Based on Cell-Free DNA and RNA. Annu. Rev. Biomed. Eng. 26, annurev-bioeng-110222-111259 (2024).","DOI":"10.1146\/annurev-bioeng-110222-111259"},{"key":"2025042023500460000_2024.05.15.24307448v2.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2113476118"},{"key":"2025042023500460000_2024.05.15.24307448v2.18","doi-asserted-by":"crossref","first-page":"e163541","DOI":"10.1172\/JCI163541","article-title":"Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers","volume":"134","year":"2024","journal-title":"Journal of Clinical Investigation"},{"key":"2025042023500460000_2024.05.15.24307448v2.19","doi-asserted-by":"crossref","first-page":"108160","DOI":"10.1016\/j.isci.2023.108160","article-title":"Chronic graft-versus-host disease is characterized by high levels and distinctive tissue-of-origin patterns of cell-free DNA","volume":"26","year":"2023","journal-title":"iScience"},{"key":"2025042023500460000_2024.05.15.24307448v2.20","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41467-019-14253-4","article-title":"Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing","volume":"11","year":"2020","journal-title":"Nat Commun"},{"key":"2025042023500460000_2024.05.15.24307448v2.21","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.tibtech.2018.01.013","article-title":"Dealing with Confounders in Omics Analysis","volume":"36","year":"2018","journal-title":"Trends in Biotechnology"},{"key":"2025042023500460000_2024.05.15.24307448v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00356-3"},{"key":"2025042023500460000_2024.05.15.24307448v2.23","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.ABL4896\/SUPPL_FILE\/SCIENCE.ABL4896_MDAR_REPRODUCIBILITY_CHECKLIST.PDF"},{"key":"2025042023500460000_2024.05.15.24307448v2.24","doi-asserted-by":"crossref","first-page":"e192974","DOI":"10.1001\/jamaoncol.2019.2974","article-title":"Factors Associated With Successful Discontinuation of Immune Suppression After Allogeneic Hematopoietic Cell Transplantation","volume":"6","year":"2020","journal-title":"JAMA Oncol"},{"key":"2025042023500460000_2024.05.15.24307448v2.25","first-page":"483","article-title":"Durable discontinuation of systemic therapy in patients affected by chronic graft-versus-host disease","volume":"108","year":"2023","journal-title":"Haematologica"},{"key":"2025042023500460000_2024.05.15.24307448v2.26","doi-asserted-by":"crossref","unstructured":"A. Chang , C. J. Loy , J. S. Lenz , A. Steadman , A. Andama , N. V. Nhung , C. Yu , W. Worodria , C. M. Denkinger , P. Nahid , A. Cattamanchi , I. De Vlaminck , Circulating Cell-Free RNA in Blood as a Host Response Biomarker for the Detection of Tuberculosis. medRxiv, 2023.01.11.23284433 (2023).","DOI":"10.1101\/2023.01.11.23284433"},{"key":"2025042023500460000_2024.05.15.24307448v2.27","doi-asserted-by":"crossref","unstructured":"C. J. Loy , A. Sotomayor-Gonzalez , V. Servellita , J. Nguyen , J. Lenz , S. Bhattacharya , M. E. Williams , A. P. Cheng , A. Bliss , P. Saldhi , N. Brazer , J. Streithorst , W. Suslovic , C. J. Hsieh , B. Bahar , N. Wood , A. Foresythe , A. Gliwa , K. Bhakta , M. A. Perez , L. Hussaini , E. J. Anderson , A. Chahroudi , M. Delaney , A. J. Butte , R. L. DeBiasi , C. A. Rostad , I. De Vlaminck , C. Y. Chiu , Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C. Cell Reports Medicine, 101034 (2023).","DOI":"10.1016\/j.xcrm.2023.101034"},{"key":"2025042023500460000_2024.05.15.24307448v2.28","doi-asserted-by":"publisher","DOI":"10.1101\/gr.276175.121"},{"key":"2025042023500460000_2024.05.15.24307448v2.29","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41564-022-01237-2","article-title":"Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults","volume":"7","year":"2022","journal-title":"Nat Microbiol"},{"key":"2025042023500460000_2024.05.15.24307448v2.30","doi-asserted-by":"crossref","first-page":"G439","DOI":"10.1152\/ajpgi.00397.2020","article-title":"Noninvasive stratification of nonalcoholic fatty liver disease by whole transcriptome cell-free mRNA characterization","volume":"320","year":"2021","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2025042023500460000_2024.05.15.24307448v2.31","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1182\/blood.2019003186","article-title":"Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE\/PBMTC 1202 studies","volume":"135","year":"2020","journal-title":"Blood"},{"key":"2025042023500460000_2024.05.15.24307448v2.32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-668251"},{"key":"2025042023500460000_2024.05.15.24307448v2.33","doi-asserted-by":"crossref","unstructured":"S. Ghimire , D. Weber , E. Mavin , X. N. Wang , A. M. Dickinson , E. Holler , Pathophysiology of GvHD and Other HSCT-Related Major Complications. Front. Immunol. 8 (2017).","DOI":"10.3389\/fimmu.2017.00079"},{"key":"2025042023500460000_2024.05.15.24307448v2.34","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2006.09.010"},{"key":"2025042023500460000_2024.05.15.24307448v2.35","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/16078454.2021.1905395","article-title":"Rate of RhD-alloimmunization after the transfusion of RhD-positive red blood cell containing products among injured patients of childbearing age: single center experience and narrative literature review","volume":"26","year":"2021","journal-title":"Hematology"},{"key":"2025042023500460000_2024.05.15.24307448v2.36","doi-asserted-by":"publisher","DOI":"10.2450\/2014.0238-13"},{"key":"2025042023500460000_2024.05.15.24307448v2.37","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/vox.13610","article-title":"RhD mismatch does not affect haematopoietic recovery, graft versus host disease and survival in allogeneic haematopoietic cell transplantation: A Japanese registry based study","volume":"119","year":"2024","journal-title":"Vox Sanguinis"},{"key":"2025042023500460000_2024.05.15.24307448v2.38","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1046\/j.1423-0410.2002.00235.x","article-title":"Alloimmunization to RhD antigen in RhD-incompatible haemopoietic cell transplants with non-myeloablative conditioning","volume":"83","year":"2002","journal-title":"Vox Sang"},{"key":"2025042023500460000_2024.05.15.24307448v2.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.03.001"},{"key":"2025042023500460000_2024.05.15.24307448v2.40","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02070508"},{"key":"2025042023500460000_2024.05.15.24307448v2.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-018-0204-7"},{"key":"2025042023500460000_2024.05.15.24307448v2.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.09.001"},{"key":"2025042023500460000_2024.05.15.24307448v2.43","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.05.15.24307448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:01:01Z","timestamp":1768507261000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2024.05.15.24307448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,16]]},"references-count":43,"URL":"https:\/\/doi.org\/10.1101\/2024.05.15.24307448","relation":{},"subject":[],"published":{"date-parts":[[2024,5,16]]},"subtype":"preprint"}}