Browsing by Author "Mohamed, Fathima A."

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    Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death
    (The American Society for Clinical Investigation, 2023-08-01) Logan, Brent R.; Fu, Denggang; Howard, Alan; Fei, Mingwei; Kou, Jianqun; Little, Morgan R.; Adom, Djamilatou; Mohamed, Fathima A.; Blazar, Bruce R.; Gafken, Philip R.; Paczesny, Sophie; Pediatrics, School of Medicine
    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.