Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death
dc.contributor.author | Logan, Brent R. | |
dc.contributor.author | Fu, Denggang | |
dc.contributor.author | Howard, Alan | |
dc.contributor.author | Fei, Mingwei | |
dc.contributor.author | Kou, Jianqun | |
dc.contributor.author | Little, Morgan R. | |
dc.contributor.author | Adom, Djamilatou | |
dc.contributor.author | Mohamed, Fathima A. | |
dc.contributor.author | Blazar, Bruce R. | |
dc.contributor.author | Gafken, Philip R. | |
dc.contributor.author | Paczesny, Sophie | |
dc.contributor.department | Pediatrics, School of Medicine | |
dc.date.accessioned | 2024-02-26T14:09:13Z | |
dc.date.available | 2024-02-26T14:09:13Z | |
dc.date.issued | 2023-08-01 | |
dc.description.abstract | BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic cell transplantation (HCT). More accurate information regarding the risk of developing cGVHD is required. Bone marrow (BM) grafts contribute to lower cGVHD, which creates a dispute over whether risk biomarker scores should be used for peripheral blood (PB) and BM. METHODS: Day 90 plasma proteomics from PB and BM recipients developing cGVHD revealed 5 risk markers that were added to 8 previous cGVHD markers to screen 982 HCT samples of 2 multicenter Blood and Marrow Transplant Clinical Trials Network (BMTCTN) cohorts. Each marker was tested for its association with cause-specific hazard ratios (HRs) of cGVHD using Cox-proportional-hazards models. We paired these clinical studies with biomarker measurements in a mouse model of cGVHD. RESULTS: Spearman correlations between DKK3 and MMP3 were significant in both cohorts. In BMTCTN 0201 multivariate analyses, PB recipients with 1-log increase in CXCL9 and DKK3 were 1.3 times (95% CI: 1.1–1.4, P = 0.001) and 1.9 times (95%CI: 1.1–3.2, P = 0.019) and BM recipients with 1-log increase in CXCL10 and MMP3 were 1.3 times (95%CI: 1.0–1.6, P = 0.018 and P = 0.023) more likely to develop cGVHD. In BMTCTN 1202, PB patients with high CXCL9 and MMP3 were 1.1 times (95%CI: 1.0–1.2, P = 0.037) and 1.2 times (95%CI: 1.0–1.3, P = 0.009) more likely to develop cGVHD. PB patients with high biomarkers had increased likelihood to develop cGVHD in both cohorts (22%–32% versus 8%–12%, P = 0.002 and P < 0.001, respectively). Mice showed elevated circulating biomarkers before the signs of cGVHD. CONCLUSION: Biomarker levels at 3 months after HCT identify patients at risk for cGVHD occurrence. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Logan BR, Fu D, Howard A, et al. Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death. J Clin Invest. 2023;133(15):e168575. Published 2023 Aug 1. doi:10.1172/JCI168575 | |
dc.identifier.uri | https://hdl.handle.net/1805/38648 | |
dc.language.iso | en_US | |
dc.publisher | The American Society for Clinical Investigation | |
dc.relation.isversionof | 10.1172/JCI168575 | |
dc.relation.journal | The Journal of Clinical Investigation | |
dc.rights | Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | |
dc.subject | Bone marrow transplantation | |
dc.subject | Transplantation | |
dc.subject | Bronchiolitis obliterans syndrome | |
dc.subject | Hematopoietic stem cell transplantation | |
dc.title | Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death | |
dc.type | Article |