An official website of the United States government
Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death.
Pubmed ID: 37526081
Pubmed Central ID: PMC10378149
Journal: The Journal of clinical investigation
Publication Date: Aug. 1, 2023
MeSH Terms: Chronic Disease, Animals, Mice, Graft vs Host Disease, Bone Marrow Transplantation, Biomarkers, Hematopoietic Stem Cell Transplantation, Matrix Metalloproteinase 3, Bronchiolitis Obliterans Syndrome
Grants: R21 HL139934, P01 HL158505, T32 AI007313, R01 CA168814, R01 CA264921
Authors: Logan BR, Paczesny S, Howard A, Blazar BR, Fu D, Fei M, Kou J, Little MR, Adom D, Mohamed FA, Gafken PR
Cite As: Logan BR, Fu D, Howard A, Fei M, Kou J, Little MR, Adom D, Mohamed FA, Blazar BR, Gafken PR, Paczesny S. Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death. J Clin Invest 2023 Aug 1;133. (15).
Studies:
- Blood and Marrow Clinical Trials Network (BMT CTN) Comparing Peripheral Blood Stem Cell Transplantation Versus Bone Marrow Transplantation in Individuals With Hematologic Cancers (0201)
- Blood and Marrow Clinical Trials Network (BMT CTN) Prospective Multi-Center Cohort for the Evaluation of Biomarkers Predicting Risk of Complications and Mortality Following Allogeneic HCT (1202)
Abstract
BACKGROUNDChronic 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.METHODSDay 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.RESULTSSpearman 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.CONCLUSIONBiomarker levels at 3 months after HCT identify patients at risk for cGVHD occurrence.FUNDINGNIH grants R01CA168814, R21HL139934, P01CA158505, T32AI007313, and R01CA264921.